Abstracts From the 42nd Annual Scientific Meeting of the Transplantation Society of Australia and New Zealand held on June 16-18, 2024

AN RCT OF INTRAVENOUS IMMUNOGLOBULIN (IVIG) VS STANDARD CARE IN CHRONIC ANTIBODY MEDIATED KIDNEY ALLOGRAFT REJECTION-VIPAR

MULLEY W 1 , THARMARAJ D 1 , POLKINGHORNE K 2 , TESCH G 1 , DAYAN S 3 , KWAN E 3 , OLSHANSKY M 4 , MARK T 5 , LEE D 6,7 , MOUNT P 7 , WONG G 8 , WYBURN K 9 , LIM W 10 , KERR P 5 , NIKOLIC-PATERSON D 5 , KANELLIS J 5

1 Departments of Nephrology and Medicine, Monash Medical Centre and Monash University, Melbourne, 2 Departments of Nephrology and Medicine and Department of Epidemiology and Preventive Medicine, Monash Medical Centre, Monash University, Melbourne, 3 Department of Anatomical Pathology, Monash Medical Centre, Melbourne, 4 Monash Genomics and Bioinformatics, Monash University, Melbourne, 5 Department of Nephrology, Monash Medical Centre, Melbourne, 6 Departments of Renal Medicine, Eastern Health, Melbourne, 7 Department of Nephrology, Austin Health, Melbourne, 8 Department of Renal Medicine and National Pancreas Transplant Unit, Westmead Hospital, Sydney, 9 Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, 10 Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth

Background: Chronic antibody mediated rejection (cAMR) is a dominant cause of kidney allograft loss but has no proven effective therapy.

Aims: To determine if IVIg is effective treatment for; and its mechanisms of action in, cAMR.

Methods: A multicentre randomised controlled trial, in patients with biopsy-proven cAMR, compared 6 doses (1gm/kg/month) of IVIg (n=15) to no-IVIg (n=15) (ACTRN12612000252819). The primary outcome was change in chronic allograft damage index (CADI) score, assessed by biopsy at 0,3,6 and 12-months. Secondary outcomes included: change in eGFR and DSA-MFI, allograft and patient survival. Intragraft gene expression was assessed by Nanostring (B-HOT panel). Outcomes were assessed using linear mixed models.

Results: Mean age was 56.1years (SD 12.1), 22 were male and mean eGFR was 41.0ml/min/year (SD 13.6). CADI scores increased in the no-IVIg group and were stable in the IVIg group (Figure, interaction, p=0.003). Over 2-years, eGFR declined more rapidly in the no-IVIg group (-10.1ml/min/year, 95% CI -13.2, -6.9) compared to the IVIg group (-3.6ml/min/year, 95%CI -6.5, -0.6, interaction p=0.003) while there were 5 graft losses and 2 deaths in the no-IVIg and 3 graft losses and no deaths in the IVIg group. DSA MFIs were not reduced by IVIg relative to no-IVIg. Intragraft expression of 59 genes (particularly B-cell related) reduced significantly with IVIg relative to no-IVIg.

Conclusions: IVIg therapy was associated with reduced deterioration in allograft injury and function in cAMR. This was not associated with reduced DSA production but may relate to intragraft effects. IVIg should be considered for patients with cAMR.

ABO INCOMPATIBLE KIDNEY TRANSPLANTS HAVE MORE EARLY REJECTION BUT COMPARABLE LONG-TERM GRAFT SURVIVAL: ANZDATA ANALYSIS

IRISH G

Transplant Epidemiology Group (TrEG), Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, South Australian Health and Medical Research Institute (SAHMRI), Adelaide

Background: ABO incompatible (ABOi) kidney transplantation accounted for 12% of living donor kidney transplants in Australia and New Zealand (ANZ) in 2022. Despite this, long term outcomes have not been evaluated in this population.

Methods: We included all ANZ adult living donor kidney transplants from 2006–2022. We used Cox proportional hazards models to assess the primary outcomes of graft and patient survival, and the secondary outcome of time to acute rejection. Due to violation of the proportional hazards assumption follow-up was split at 1 month for graft survival and rejection.

Results: 5161 kidney transplants occurred, of which 629 (12.2%) were ABOi. ABOi transplant recipients were older (median age: ABOi:50 years IQR:36-58, ABO compatible (ABOc):47 years IQR:35-58) and more frequently male (ABOi:68.5%, ABOc:62.5%). There was no difference in graft survival between ABOi and ABOc recipients (month 1 aHR:1.21 95%CI 0.51-2.88; p=0.66, >1 month aHR:0.86 95%CI 0.69-1.07; p=0.18)). Patient survival was not different (aHR:0.80 95%CI 0.61-1.03; p=0.09). However, ABOi recipients experienced higher acute rejection rates within one month (month 1 aHR:1.66, 95%CI 1.34–2.05; p<0.00) with increased acute antibody mediated (month 1 aHR:3.12, 95%CI 2.19–4.48; p<0.001) and cellular rejection episodes (month 1 aHR:1.43 95%CI 1.10–1.85; p=0.007). There were no statistically significant differences in acute rejection after one month.

Conclusions: ABOi transplantation in ANZ is associated with an increased rate of early rejection compared with ABOc transplantation, but equivalent patient and graft survival. These results support the continuation of ABOi transplantation for selected patients.

MEMORY B CELLS, T-FOLLICULAR HELPER and T-REGULATORY-1 CELLS IN KIDNEY TRANSPLANT RECIPIENTS WITH ANTIBODY-MEDIATED REJECTION

SINGLETON K 1 , ROSALES B 2 , WAN S 3 , DE LA MATA N 4 , GUNASEGARAN B 5 , WEBSTER A 6 , MCGUIRE H 2 , FAZEKAS B 7 , WYBURN K 8

1 School of Medicine, Faculty of Health Sciences, University of Sydney, 2 Sydney School of Public Health, Charles Perkins Centre Renal Research Node, University of Sydney, 3 School of Public Health, Department of Renal Medicine and Transplantation, Department of Renal Medicine, Charles Perkins Centre Renal Research Node, University of Sydney, Royal Prince Alfred Hospital, Royal North Shore Hospital, University of Sydney, 4 School of Public Health, University of Sydney, 5 Ramaciotti Facility for Human Systems Biology, University of New South Wales, 6 School of Public Health, Renal Medicine and Transplantation Research, University of Sydney, Westmead Hospital, 7 Ramaciotti Facility for Human Systems Biology, University of Sydney, 8 Department of Renal Medicine and Transplantation, Charles Perkins Centre Renal Research Node, Royal Prince Alfred Hospital, Sydney, The University of Sydney

Aims: We sought to characterise changes in B-memory (B mem ) and T-follicular helper (TFH) cell subsets in patients who developed antibody-mediated rejection (ABMR) and stable recipients, in pre- and post-transplant samples.

Methods: T FH , T-regulatory-1 (TR1), and switched and unswitched B mem cells were identified in peripheral blood of a cohort of 22 kidney transplant recipients (12 with stable function and 10 with ABMR) via cytometry by time-of-flight. We identified CD19+CD27+CD24+ B mem cells, subtyped into switched (IgD-) and unswitched (IgD+) (Fig 1a), and CD4+CXCR5+ T FH cells, subtyped into CCR5+PD-1+ TR-1 cells (Fig 1b) using manual gating. Students’ t-tests were used to compare cell populations in recipients.

Results: We found a higher proportion of CD27+ B-cells in ABMR than stable patients at day 7 (p=0.07) and day 30 (p=0.02), but no statistical difference pre-transplant. Higher proportion of switched relative to unswitched B mem cells in ABMR vs stable recipients at pre-transplant (p=0.05), day 7 (p=0.05), day 90 (p=0.02), and day 30 (p=0.09). The average proportion of TR1 within T FH cells decreased in recipients with ABMR (mean -1.7, IQR -3.13 - -0.30) and increased in stable recipients (mean 0.3, IQR -0.65-1.77) from pre-transplant to day 7 (p=0.01).

Conclusion: An increased proportion of switched/unswitched B-memory cells and a decreased proportion of regulatory T cells/ TFH were observed in ABMR compared to stable recipients across several time points. Correlation to rejection timepoint and a larger cohort study may provide further understanding of underlying mechanisms and provide insights into predicting rejection risk.

Figure 1: a) Manual B-cell gating protocol ; samples were gated for CD3-CD14-CD8-CD4-CD20+CD19+ singlets, then CD27+ (memory) cells identified as unswitched (CD24+IgD+) or switched (CD24+IgD-);

Figure 1 b) Manual T-cell gating protocol ; samples were gated for CD3+CD19-CD14-CD20-IgM- singlets, then CD4+ (T H ) cells gated as CD25-CD127+CD95+ (activated conventional T-cells). CXCR5+ T FH cells selected for, and the PD1+CCR5+ TR1 subset identified

HYPOTHERMIC OXYGENATED MACHINE PERFUSION REDUCES INCIDENCE OF NON-ANASTOMOTIC BILIARY STRICTURES IN DCD LIVER TRANSPLANTS

WALCOTT J 1 , FIORE B 2 , VIJAYANAND D 2 , PRASAD R 2

1 Transplant Surgery, Princess Alexandra Hospital, Brisbane, 2 Hepatobiliary and Liver Transplant Unit, St James’s University Hospital, UK

Aims: Hypothermic oxygenated machine perfusion (HOPE) has been shown to reduce the incidence of non-anastomotic biliary strictures (NAS), acute kidney injury (AKI) and early allograft dysfunction (EAD) in DCD livers compared with static cold storage (SCS). The aim of this study is to assess the outcomes of the largest UK cohort of DCD liver transplants using HOPE.

Method: Data from HOPE-DCD liver transplants since October 2020 were prospectively collected. Outcomes including EAD, NAS, AKI and need for dialysis, were compared against an historical cohort of SCS-DCD liver transplants.

Results: 40 HOPE-DCD liver transplants were included in this study compared with 80 SCS-DCD. Median follow up was 17.4 months for HOPE-DCD and 47.6 for SCS-DCD. Mean time on HOPE perfusion was 162 mins (± 51). The 12-month graft survival was 91.7% vs 87.5% (p=0.51) for HOPE and SCS respectively. EAD occurred in 25.0% of HOPE-DCD compared to 41.3% for SCS-DCD (0.48, CI 0.20-1.10, p=0.08). 10% of HOPE-DCD patients required dialysis compared to 20% in SCS-DCD (OR 0.44, CI 0.14-1.43, p=0.17). Incidence of NAS was 5% for HOPE-DCD, compared to 25% for SCS-DCD (OR 0.15, CI 0.04-0.71, p=0.02). Of the 22 cases of NAS, there were no cases of graft loss for those treated with HOPE compared with 7 cases of graft loss (35%) for those that were not (p=0.31), with a median graft survival of 8.8 months in this group.

Conclusion: This study demonstrates a reduction in the incidence of NAS for HOPE-DCD liver transplantation.

DEVELOPING A NORMOTHERMIC REGIONAL PERFUSION SERVICE: THE EARLY LEARNING EXPERIENCE

SUTHANANTHAN AE , CLARKE G, HALLE-SMITH J, PAPAMICHAIL M, RAZA S, MANGCO J, NUTU A, DASARI B, BARTLETT D, MATEOS RS, ROBERTS K, PERERA T, MERGENTAL H

Liver Surgery, Queen Elizabeth Hospital, Birmingham, UK

Introduction Utility of Normothermic Regional Perfusion (NRP) is now established in the post-mortem assessment and optimisation of cardiac-death (DCD) organ donors. DCD-NRP organ retrievals is predicted to become routine practice in the United Kingdom over the next decade. However, establishing a new service involving novel technology remains challenging; with high technical, logistical, and knowledge demands. This narrative explores the step-by-step process we undertook to establish our NRP programme, and our initial results.

Methods: Stakeholder engagement and support from surgeons, anaesthetists, intensivists, hepatologists and management was key in the initial steps of developing the programme. The commissioning phase included obtaining appropriate funding, surgeon and perfusionist training, and establishing mentorship under established UK centres. Service provision began in February 2022 with a single surgeon and perfusionist offering an ad-hoc service, later expanding as we accrued experience.

Results: Over 24 months, we attended 27 NRP retrievals (Figure 1) from which 43 kidneys and 13 livers have been transplanted. Three livers initially declined by all centres were assessed in-situ and successfully transplanted with good patient outcomes. Our centre is now independent for the provision of NRP services; with the team expanded to 3 NRP surgeons and 3 NRP perfusionists. In our DCD-NRP cohort, no incidences of ischaemic-type biliary lesions or primary non-function have been identified, with 100% 90-day graft and patient survival.

Conclusion: Establishing an NRP programme presents significant challenges with a steep learning curve which once navigated, can be rapidly expanded with improved organ utility and graft outcomes.

IS EX-SITU NORMOTHERMIC MACHINE PERFUSION THE NEXT STEP IN PAEDIATRIC LIVER TRANSPLANTATION?

NIU A , LAU N, LY M, YOUSIF P, RISBEY C, BABEKUHL D, LIN YS, MCKENZIE C, LIU K, KENCH, MCCAUGHAN G, CRAWFORD M, PULITANO C

Transplant Department, Royal Prince Alfred Hospital, Sydney

Background: Paediatric patients are currently excluded from ex-situ normothermic machine perfusion (NMP) of livers due to challenges of perfusing smaller grafts, risk of portal hyperperfusion injury, and preference to utilise optimal grafts. We aim to evaluate the use of a preclinical model to perfuse left lateral segment grafts (LLSG) using NMP.

Methods: Human livers were split into LLSG and extended right grafts (ERG) and perfused using our long-term NMP protocol. The LLSG consisted of segments 2 and 3 with the coeliac trunk, left portal vein and left hepatic duct, to simulate a realistically sized split graft used in clinical practice. Portal hyperperfusion was determined through venous and arterial haemodynamic parameters. Biochemical markers of portal hypertension were measured. Hyperperfusion injury was assessed using histopathological signs of small for size syndrome (portal tract, lobular, regenerative, and vascular changes).

Results: Ten LLSGs, including 6 from DCD donors, were included. The mean survival time was 6.7 days, with the one graft surviving up to 13 days. LLSGs had higher perfusion parameters than ERGs, requiring higher portal vein pressure targets for adequate flow, and increased hepatic artery pressures and flows. There was no difference in histological signs of hyperperfusion injury between LLSGs and ERGs. Endothelin-1 levels, reflecting portal hypertension and endothelial cell dysfunction, did not increase.

Conclusion: This is the first preclinical model to demonstrate that NMP of LLSGs is technically possible without apparent portal hyperperfusion injury. This opens the opportunity to expand the use of marginal grafts (including DCD donors) in paediatric liver transplantation.

ESTABLISHMENT OF EX VIVO NORMOTHERMIC MACHINE PERFUSION TO SUPPORT ASSESSMENT AND UTILISATION OF MARGINAL DONOR KIDNEYS

SOH QR 1 , BAGHANI-AVAL H 1 , EZHILARASU J 1 , FURTADO R 1 , STEVEN M 1 , SKENE A 2 , PEFANIS A 3 , WHITLAM JB 1 , HE B 1

1 Kidney Transplant Service, Austin Health, Victoria, Australia, 2 Department of Anatomical Pathology, Austin Health, Victoria, Australia, 3 Department of Medicine, The University of Melbourne, Australia

Aims: This pilot study examines the role of ex vivo normothermic machine perfusion (NMP) in the evaluation of deceased donor kidneys at increased risk of non-utilisation. We aim to develop local experience with NMP for a clinical study.

Methods: In collaboration with DonateLife Victoria and with consent of donor families, six deceased donor kidneys that were declined for use in transplantation were perfused with a red blood cell-based perfusate for 2 hours using an ex vivo NMP. Kidneys were evaluated using Nicholson & Hosgood criteria through macroscopic assessment, measurement of renal blood flow, and urine output. Perfusate samples were collected for blood gas and electrolyte analysis, and kidney biopsies were collected pre- and post NMP.

Results: All six kidneys (two DCD, four DBD) showed excellent perfusion on macroscopic assessment (scoring 1), with all producing urine. The median urine output was 480 mL over 2 hours, and median renal blood flow was 196 mL/minute. The perfusate (intrinsic) creatinine level decreased significantly over the perfusion period from 151 to 82 µmol/L (p=0.02). Histopathology showed a Remuzzi score of ≤3 in all cases (Figure 1, 2).

Conclusion: In this small cohort, all 6 non-utilised deceased donor kidneys demonstrated viability and early function with no instances of failed perfusion. This pilot study successfully established the necessary skills and processes for ex vivo NMP of kidneys at our centre and will now be translated to a clinical trial. The significant reduction in perfusate (intrinsic) creatinine levels presents an interesting finding that merits further investigation.

Figure 1: Pre NMP (image on left) and Post NMP (image on right)

POTENTIAL DONOR FAMILIES’ BEHAVIOUR AND EXPERIENCES FOLLOWING THE ORGAN DONATION DEEMED CONSENT ACT 2019 IN ENGLAND

MC LAUGHLIN L 1 , NOYES J 1 , AL-HABOUBI M 2 , WILLIAMS L 2 , BOSTOCK J 2 , BOADU P 2 , MAYS N 2

1 School of Medical and Health Sciences, Bangor University, UK, 2 Policy Innovation Research Unit, London School of Hygiene and Tropical Medicine, UK

Aim: In May 2020, England implemented “deemed consent” legislation to reduce barriers to consent for deceased organ donation. We studied the experiences, behaviour and decisions of families who were approached about organ donation after their relative died to understand better how families influenced consent rates.

Methods: Semi-structured interviews with people involved in organ donation discussions, feedback from specialist nurses, comparisons with routine potential donor audit data, stakeholder feedback and public involvement. Framework analysis informed by utilitarian theory.

Results: 103 participants were interviewed representing 83 cases. 31/83 (37%) cases fully supported organ donation, 41/83 (37%) supported retrieval of some organs, tissues and procedures and 11/83 (13%) declined completely. Overall consent rates have fallen since implementation. Families struggled to comprehend the complex processes involved in organ donation. Specialist nurses were critical in supporting families. Families most frequently asked themselves if their relative would have wanted to have the retrieval surgery, rather than whether the deceased wanted to save lives. Families unpicked the deceased’s decision in life and superimposed their own values and judgements to challenge and overturn consent.

Conclusion: Despite a change in legislation, family behaviour did not appear to align with the utilitarian assumptions implicit in the 2019 Act to benefit people requiring transplants. Family members not supportive (of deemed consent, in particular) believed that donation would cause them and the deceased additional harms. They opted for what they thought would benefit them or their family the most rather than to provide the maximum benefit to unknown others.

A REVIEW OF DELAYED GRAFT FUNCTION in ANZKX PROGRAM 2021-2023: IMPACT OF ISCHAEMIA TIMES ON TRANS TASMAN EXCHANGES

MCGINN S 1 , VANHARDEVELD E 2 , JONES B 2 , CANTWELL L 3 , KUMMROW M 3 , BURTON J 4 , DITTMER I 4 , HUGHES P 2

1 Renal and Transplantation Unit, Royal North Shore Hospital, 2 Renal and Transplantation Unit, Royal Melbourne Hospital, 3 ANZKX and Tissue Typing Laboratory Victoria, Australian Red Cross Life Blood, 4 Renal and Transplantation Unit, Auckland City Hospital, New Zealand

With new Trans-Tasman routes for Australian and New Zealand Paired Kidney Exchange Program (ANZKX) the risk of increased cold ischaemic times may impact on delayed graft function rates.

Aims: An audit of ischaemic times has been performed to assess the impact on delayed graft function (DGF) (as per ANZDATA definition).

Methods: . ANZKX has collated outcome data from participating units at one-month post-transplant since January 2021. A retrospective review was done to assess factors that may impact on delayed graft function.

Results: 193 kidney transplants occurred from 1 January 2021-31 December 2023. The incidence of delayed graft function was 5.7% (11 patients). All were left kidneys and 7 had multiple vessels. There were 28 Trans-Tasman and 14 East-West Coast transplants, and none had delayed graft function. The average cold ischaemic time for Trans-Tasman exchanges was 10 hours 40 mins ± 33 mins.

The cold ischaemic time for transplants with DGF was 6 hours 32 mins ±54 mins and was similar to those with immediate graft function (IGF) 6 hours 54 mins ±13mins.

Mean donor age was similar between DGF and IGF patients at 51 ± 3 years. 8 of the recipients with DGF were on dialysis and 2 had previous transplants.

Conclusions: Trans-Tasman exchanges are associated with a cold ischaemic time of over 10 hours. However, the incidence of delayed graft function in ANZKX transplants does not correlate with longer cold ischaemic times and other contributing factors need to be explored. Patients can be reassured that Trans- Tasman exchanges are associated with good outcomes.

ADVANCED DONOR AGE DOES NOT IMPACT GRAFT SURVIVAL IN A LARGE SINGLE CENTRE LUNG TRANSPLANT COHORT

DARIE A , LEVVEY B, SHINGLES H, PARASKEVA M, LEVIN K, WESTALL G, SNELL G

Lung Transplant Service, Alfred Hospital, Melbourne

Introduction The scarcity of donor lungs for lung transplant (LTx) drives wait-list mortality for patients with end-stage lung disease. Thus, LTx centres in Australia and Europe have increasingly accepted age-extended criteria donor lungs for LTx- a practice not common in the USA. Nevertheless, long term data on older lung graft outcomes is limited.

Methods: In this single-centre, retrospective analysis we included 1114 LTx performed at The Alfred between 2010- 2024 and compared graft survival (ie time to death or re-LTx) outcomes between donors aged < or ≥65years. All potential donors ≥65 yrs had mandatory chest CT assessment.

Results: Mean age of LTx recipients was 52±16yrs, 56.5% were male and the mean follow-up was 4.8±3.5yrs. The most prevalent LTx indication was COPD (37%). Older donors were used in 146/1114 (13%) of all LTx. LTx recipients of older donors were themselves older 58 ± 11yrs vs 52 ± 16 yrs, p<0.001. However, there was no difference in graft survival for older donor lungs (median graft survival <65 yrs 8.3±0.5 vs ≥65yrs 8.5±0.5 yrs, p=0.255, or <70 yrs 8.5±0.6 vs ≥70yrs 8.5±0.5 years, p=0.186). Additionally, there was no difference in the cause of death (malignancy vs infection vs CLAD vs other, p=0.438). Re-LTx occurred more often in the younger donor group (5.2% vs 1.4%, p=0.043).

Conclusions: Contrary to earlier US reports, graft survival is similar for lungs retrieved from donors <65, compared with donors ≥65(or even 70 yrs). Appropriately assessed age-extended lungs should be routinely considered for clinical LTx.

Figure 1 . LTx Graft survival according to donor age

KIDNEY TRANSPLANTATION OUTCOMES FROM UNCONTROLLED DONATION AFTER CIRCULATORY DEATH: A SYSTEMATIC REVIEW AND META-ANALYSIS

SCHRODER H 1 , VIJAYAN K 1 , HAMEED A 2 , HITOS K 2 , LO W 3 , LAURENCE J 4 , YOON P 2 , NAHM C 2 , LIM W 5 , LEE T 2 , YUEN L 2 , WONG G 6 , PLEASS H 2

1 School of Medicine, University of Sydney, 2 Department of Surgery, Westmead Hospital, Sydney, 3 Institute of Urology and Nephrology, Kuala Lumpur General Hospital, Malaysia, 4 Royal Prince Alfred Hospital, Sydney, 5 Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, 6 Department of Renal Medicine, Westmead Hospital, Sydney

Background: Uncontrolled donation after circulatory death (uDCD) is a potential additional source of donor kidneys. This systematic review investigated uDCD kidney transplant outcomes to determine if these are comparable to controlled donation after circulatory death (cDCD).

Methods: MEDLINE, Cochrane and Embase databases were searched. Data on demographic information and transplant outcomes were extracted from included studies. Meta-analyses were performed, and risk ratios (RR) were estimated to compare transplant outcomes from uDCD to cDCD.

Results: Nine cohort studies were included, from 2178 uDCD kidney transplants. There was a moderate degree of bias, as four studies did not account for potential confounding factors. The median incidence of primary non-function (PNF) in uDCD was 12.3%, versus 5.7% for cDCD (RR: 1.85; 95% CI 1.06-3.23; P=0.03, I 2 =75). The median rate of delayed graft function (DGF) was 65.1% for uDCD and 52.0% for cDCD (RR: 1.27; 95% CI 1.09-1.48; P=0.002; I 2 =74%). The median 1-year graft survival for uDCD was 82.7% compared to 87.5% for cDCD (RR: 1.43.; 95% CI 1.02-2.01; P=0.04, I 2 =71%). The median 5-year graft survival for uDCD and cDCD was 70% each. Notably, the use of normothermic regional perfusion (NRP) improved PNF rates in uDCD grafts.

Summary: In conclusion, if uDCD grafts survive beyond the first year, longer term outcomes are comparable to cDCD, which may be facilitated by technologies such as NRP. Therefore, uDCD kidneys could be used to expand the donor pool within Australia and New Zealand.

SUBLINGUAL MICROCIRCULATION AND FRAILTY: INSIGHTS FROM KIDNEY TRANSPLANT CANDIDATES

HOMES R 1 , GORDON E 2 , HUBBARD R 2 , FRANCIS R 2 , GIDDINS F 2 , MIDWINTER M 1

1 School of Biomedical Science, The University of Queensland, 2 Centre for Health Services Research, The University of Queensland

Aims: Frailty, marked by a decline in physiological reserves, is more prevalent among those with chronic kidney disease. Maintaining healthy tissue largely depends on adequate microcirculation. There is a hypothesis suggesting that dysregulated microcirculation may contribute to the reduced physiological reserve in frail individuals. This study examines the relationship between frailty index scores, altered gait, strength (phenotypical traits), and sublingual microcirculatory health in a population eligible for renal transplant candidacy.

Methods: The study involved 44 participants (22 male and 22 female) aged between 46 and 64, attending the Transplant Assessment Clinic at the Queensland Kidney Transplant Service in Brisbane, Australia. Microcirculatory measurements were obtained sublingually using the AVA MicroScan system, adhering to the parameters specified in the roundtable manuscript. Gait analysis utilized the LEGSYS+ system, while strength was assessed using a handgrip dynamometer equipped with a 300KG load cell. Frailty was evaluated through the Rockwood frailty index questionnaire. Univariate analysis was performed to assess the relationship between Frailty Index scores and these parameters, with their significance ranked using machine learning.

Results: Significant associations were observed between the Frailty Index (FI) and all microcirculatory and strength parameters, while no associations were found with gait parameters. Machine learning identified microcirculation parameters as the strongest predictors of frailty index scores.

Conclusions: In summary, FI scores correlated with a decline in microcirculatory health and strength, but not gait. Machine learning emphasised microcirculation parameters as the key predictors, providing insight on the underlying physiological reserve decline of frailty in renal disease patients.

HIGH RESOLUTION GENOMIC HLA TYPING IN DECEASED DONOR KIDNEY TRANSPLANTATION

LIM Z 1 , CHAU M 1 , LOPEZ DA CRUZ P 2 , LE C 3 , FARZANEH BOROUMAND F 4 , GATELY R 5 , TAVERNITI A 6 , TEIXEIRA-PINTO A 4 , WONG G 7 , LIM W 1

1 Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, 2 School of Medical and Health Sciences, Edith Cowan University, Joondalup, 3 Department of Clinical Immunology, PathWest, Fiona Stanley Hospital, 4 School of Public Health, University of Sydney, 5 Nephrology and Renal Transplant, Princess Alexandra Hospital, Brisbane, 6 Centre for Kidney Research, The Children’s Hospital at Westmead, Sydney, 7 Renal Transplant Unit, Westmead Hospital, Sydney

Aim: HLA compatibility remains the standard triage test for the allocation of deceased donor kidneys in Australia. Low/intermediate-resolution molecular HLA typing is typically available at the time of allocation, but given the importance of HLA matching, we aimed to determine whether high-resolution molecular HLA typing can identify missed HLA mismatches and improve post-transplant allo-immune risk stratification.

Methods: Consecutive deceased-donor/recipient pairs from a single centre between 2016-2020 were retyped using high-resolution next-generation sequencing (NGS) at HLA-A,-B,-DRB1 and extended alleles (HLA-C,-DRB3/4/5,-DQA,-DQB,-DPA,-DPB). We compared the number of HLA-mismatches and development of dnDSA between NGS vs. low/intermediate-resolution typing results. C-statistics for each model evaluating the association between low/intermediate-resolution typing at HLA-A,-B,-DRB1, NGS-typing at HLA-A,-B,-DRB1, and NGS-typing at the extended alleles were calculated.

Results: Of 179 donor/recipient pairs, 92 (51%) developed acute rejection (79/92 acute cellular, 13/92 antibody-mediated rejection). NGS-typing identified an additional 16 (9%) HLA-A mismatches, 16 (9%) HLA-B mismatches, and 60 (33%) HLA-DRB1 mismatches compared to low/intermediate resolution typing. The C-statistics of the models for acute rejection of low/intermediate-resolution typing at HLA-A,-B,-DRB1, NGS-typing at HLA-A,-B,-DRB1, and NGS-typing at the extended alleles were 0.59, 0.61 and 0.59 (p>0.05 across groups). Of the additional mismatches identified by NGS-typing (but matched by low/intermediate-resolution typing), 2 (9.5%) of dnDSA were directed against HLA-A, none against HLA-B and none against HLA-DRB1 loci.

Conclusion: NGS-typing provides a more accurate assessment of HLA compatibility and may identify those who may develop dnDSA post-transplant. However, NGS-typing at HLA-A,-B,DRB1 or at the extended alleles do not improve the discrimination for acute rejection compared to low/intermediate-resolution typing.

GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONISTS FOR WEIGHT LOSS IN HEART FAILURE PATIENTS CONSIDERED FOR HEART TRANSPLANTATION

JEYAKUMAR S 1 , JEYAKUMAR R 1 , ROBSON D 2 , HONEYSETT L 2 , RAVEN L 3 , DEVEZA R 2 , JABBOUR A 2 , KOTLYAR E 2 , KEOGH A 2 , GREENFIELD J 2 , MACDONALD P 2 , HAYWARD C 2 , MUTHIAH K 2

1 University of New South Wales, 2 St Vincent’s Hospital, Sydney, 3 Garvan Institute of Medical Research, Sydney

Aims: Morbid obesity is a major exclusion criterion for heart transplantation, with a body mass index (BMI) <35 kg/m 2 recommended prior to transplant listing per current guidelines. There is limited research into the safety and efficacy of GLP-1 RA for weight loss as a bridge to candidacy for heart transplantation.

Methods: We retrospectively analysed medical records of outpatients with end-stage heart-failure (ESHF) being considered for heart transplantation at our institution between June 2022 and October 2023. Recruited patients were commenced on 1mg subcutaneous semaglutide weekly, and demographic data, cardiac function, and transplant listing status were evaluated pre- and post-GLP-1 RA use.

Results : Nine patients (100% male, mean age: 54.5 ± 8.2 years) with ESHF (mean LVEF: 19.4 ± 0.1%) and severe obesity (mean pre-GLP-1 RA BMI: 36.3 ± 3.4 kg/m 2 ) were prescribed semaglutide for a mean duration of 5 months (range: 1 – 16 months). All patients experienced substantial weight loss with GLP-1 RA (mean post-GLP-1 RA BMI: 34.7 ± 2.5 kg/m 2 ); pairwise comparisons showed a mean BMI reduction of 1.6 kg/m 2 (mean weight change: –4.8kg). Subsequently, 7 patients (77.8%) were transplant listed and continued on GLP-1 RA, and 1 patient underwent heart transplantation (11.1%). No significant adverse effects were observed in any patient.

Conclusion: We have demonstrated for the first time, GLP-1 RA are a safe and effective bridge to heart transplantation candidacy for patients with severe obesity, allowing life-saving treatment in patients otherwise precluded from transplantation. Larger studies will inform the inclusion of GLP-1 RA in transplant guideline.

ACCESS TO KIDNEY TRANSPLANT WAITLISTING FOR NSW MENTAL HEALTH SERVICE USERS

BRODZELI A 1 , BALDWIN H 1 , DE LA MATA N 1 , WEBSTER A 1 , GRANT S 2

1 School of Public Health, University of Sydney, 2 InforMH, NSW Ministry of Health

Aims: We aimed to describe whether people with prior mental health (MH) service use experience delayed access to waitlisting for Kidney Replacement Therapy (KRT) compared to other NSW residents.

Methods: Data from ANZDATA linked with NSW administrative datasets from the Mental Health Living Longer cohort were used including all adult patients receiving KRT in NSW, 2006-2020. Rates of prior MH service contact were described, and a subgroup with evidence of severe and persisting mental illness (SPMI) defined. Time to waitlisting from start of KRT was estimated by mental health status using Kaplan-Meier estimates.

Results: Of 11,536 patients in the study population, 2,089 (18.2%) were identified as MH service users, including 641 (5.6%) with SPMI, and 1448 (12.6%) with other MH conditions. MH service use predated KRT for 531 (82.8%) of the SPMI group and 820 (56.6%) other MH service users. Females comprised a higher proportion of the SPMI group (41.2%) compared to the other MH (36.1%) and no MH (36.1%) groups. MH service users were younger (SPMI mean age 53.2, other MH 57.2) than those with no MH (63.5 years). Crude time to waitlisting by MI is shown in Figure 1. In total, 22.1% of patients were waitlisted.

Conclusions: Preliminary results suggest delayed KRT access for people with SPMI, but earlier access for people with other MH conditions, compared to those without MH service use. Further analysis is needed to account for potential confounders. Our findings will assist to understand inequities in health care delivery for people living with mental illness and chronic kidney disease.

Figure 1. Kaplan-Meier curve for time to waitlisting for kidney dialysis patients by pre-existing mental health service user status, NSW 2006-2020

CHANGES IN B CELL PHENOTYPES IN PERIPHERAL BLOOD OF PATIENTS WITH LONG-SURVIVING RENAL TRANSPLANT

RAKESH P 1 , ZAHOROWSKA B 2 , DIEP J 2 , CHEUNG J 2 , WU P 2 , AL-ATIYAH R 1 , SURANYI M 2 , SPICER T 2 , WONG J 2 , TRAN G 1 , HODGKINSON SJ 3 , HALL BM 4 , VERMA ND 1

1 Immune Tolerance Group, Ingham Institute for Applied Medical Research and South West Sydney Clinical School, University of New South Wales, 2 Renal Unit, Liverpool Hospital, 3 Immune Tolerance Group and The Department of Neurology, Ingham Institute for Applied Medical Research and South West Sydney Clinical School, University of New South Wales and Liverpool Hospital, 4 Immune Tolerance Group and Renal Unit, Ingham Institute for Applied Medical Research and Liverpool Hospital

Background and Aims: Studies on renal transplant recipients with operational tolerance have identified changes in B cell subsets. We studied B cells in renal transplant patients with a graft surviving >10years (RT) on immunosuppression. Populations of CD4 + and CD8 + T cells, NK cells, B cells, and B cell subpopulations of RT (n=23) were compared to healthy volunteers (HV, n=13).

Methods: T, B and NK cells were examined using a 6-colour TBNK reagent (BD) (CD3/CD4/CD8/CD45/CD19/CD16&CD56). Peripheral blood mononuclear cells (PBMC) isolated from the remaining blood were stained with monoclonal antibodies (CD19/CD21/CD24/CD27/CD38/CD45/IgD/IgM) to identify B cell subpopulations. Data was acquired on BD FACSCanto II using BD FACSDiva software (v8.0) and analysed using FlowJo.

Results: TBNK staining revealed RT had significantly less lymphocytes and B cells compared to HV. Staining PBMC with a panel of B cell-related antibodies showed significant reduction in CD19 + cells in RT compared to HV. There were less CD21 hi and more CD21 lo cells in RT than HV. Switched memory B cells and plasmablasts were higher in RT than HV. Transitional B cells in RT appeared lower than HV but was statistically insignificant. Upon examining Treg to B cells ratio, RT showed significantly higher proportions of activated Treg (CD4 + CD25 + CD127 lo CD45RA - Foxp3 +/hi ) to B cells, compared to HV. There were no significant differences between the two groups in naïve Treg to naïve T cell ratio, or highly activated Treg to activated effector T cells.

Conclusions: Higher proportions of Treg to B cells may be clinically relevant and potentially demonstrate increased immunological suppression in long-surviving renal transplant recipients.

STATUS OF LIVER TRANSPLANTATION FOR CHOLANGIOCARCINOMA AND MIXED-TYPE HEPATOCELLULAR CARCINOMA IN ANZ (COMIT-ANZ)

RIDDIOUGH G 1 , KAT H 1 , BYRNE M 2 , KILBURN D 3 , BROWN K 3 , KRISHNAN A 3 , GOH SK 4 , MARSHALL-WEBB M 4 , PULITANO C 5 , CHAN K 6 , PHILIPOFF A 7 , NAZAAR A 8 , LEE E 1

1 Department of Surgery, Austin Health, Victoria, 2 ANZLITR, Austin Hospital, Victoria, 3 Department of Surgery, Princess Alexandra Hospital, Brisbane, 4 Department of Surgery, Flinders Medical Centre, Adelaide, 5 Department of Surgery, Royal Prince Alfred Hospital, Sydney, 6 Transplant Surgery, Royal Prince Alfred Hospital, Sydney, 7 Department of Surgery, Sir Charles Gairdner Hospital, Perth, 8 Department of Surgery, Auckland City Hospital, New Zealand

Aims: Assess the outcomes and identify factors which predict long term survival for patients undergoing liver transplantation (LT) for cholangiocarcinoma (CCA) and mixed-type hepatocellular-cholangiocarcinoma (HCC-CCA) in Australia and New Zealand (ANZ).

Methods: A collaborative retrospective multi-centre study enrolled all transplant centres within ANZ. To our knowledge, this is the first study of this nature in ANZ. Data was collected by transplant fellows into a REDCaps Database. Data was retrieved and analysed centrally at the lead site, Austin Health. Results: 64 patients (48 males, 16 females) underwent LT in the setting of CCA or HCC-CAA in ANZ since records began in 1988. 16 patients were diagnosed with CCA prior to LT, the remaining (n=48) CCAs and HCC-CCAs were detected incidentally on explant histology. Overall, 48 (75%) patients had CCA, of which, 27 (56%) were intrahepatic CCAs (iCCA). Median overall survival (mOS) and median recurrence free survival (mRFS) for all-comers post LT for CCA/HCC-CCA was 36 and 31 months respectively, and for CCAs only 31 and 23 months respectively. mOS and mRFS for iCCAs was 41 and 38 months respectively, and for pCCAs was 23 and 16 months respectively. mOS and mRFS for single iCCAs <2cms (n=7) was 59 and 59 months respectively.

Conclusions: ILTS Guidelines 2020 support LT as a viable treatment for achieving mid-long term survival for “very early” iCCAs (single nodule <2cms) and for unresectable perihilar CCAs after neoadjuvant chemoradiation. Data presented here representing the entire ANZ experience in LT for CCA and HCC-CCAs supports application of these guidelines to the ANZ population.

EXAMINATION OF SUBSETS OF CD4+ LYMPHOCYTE SUBPOPULATIONS IN LONG-SURVIVING RENAL TRANSPLANT PATIENTS

RAKESH P 1 , ZAHOROWSKA B 2 , DIEP J 2 , CHEUNG J 2 , WU P 2 , AL-ATIYAH R 1 , SURANYI M 2 , SPICER T 2 , WONG J 3 , TRAN G 1 , HODGKINSON SJ 4 , HALL BM 5 , VERMA ND 1

1 Immune Tolerance Group, Ingham Institute for Applied Medical Research and South West Sydney Clinical School, University of New South Wales, 2 Renal Unit, Liverpool Hospital, 3 Immune Tolerance Group, Liverpool Hospital, 4 Immune Tolerance Group and The Department of Neurology, Ingham Institute for Applied Medical Research and South West Sydney Clinical School, University of New South Wales and Liverpool Hospital, 5 Immune Tolerance Group and Renal Unit, Ingham Institute for Applied Medical Research and Liverpool Hospital,

Background and Aims: CD4 + cells can mediate renal transplant rejection or tolerance. Miyara et al. identified five populations (Pop) within CD4 + T cells based on CD45RA and CD25/Foxp3 expression. Pop I, II and III are Treg; naïve Pop I (CD45RA + Foxp3 + ), activated Pop II (CD45RA - Foxp3 hi ), and cytokine-secreting Pop III (CD45RA - Foxp3 + ), which includes activated effector cells. Pop IV are activated (CD45RA - Foxp3 - ), and Pop V are naïve T cells (CD45RA + Foxp3 - ). Changes within these lymphocyte subsets may indicate transplant tolerance or identify patients who can reduce immunosuppression. We examined Pop I-III of CD4 + CD25 + CD127 lo Treg and IV-V of CD4 + T cells in blood of renal graft recipients with grafts surviving >10years (RT, n=25) compared to healthy volunteers (HV, n=44).

Methods: Peripheral blood mononuclear cells (PBMC) isolated from HV and RT blood were examined using flow cytometry for Treg (CD4/CD25/CD127/CD45RA/Foxp3), chemokine receptors (CXCR3, CCR4, CCR6, CCR7), and Treg activation/suppression-related molecules (CD39/HLA-DR/PD-1).

Results: RT had less lymphocytes and Treg compared to HV. RT had less Pop I and Pop V but higher Pop IV than HV. There were significantly less CXCR3 + cells in RT than HV in Pop I, II, III and IV. RT had fewer CCR6 + cells compared to HV in Pop II, III and V. RT had less CCR7 + cells in Pop I, IV and V, but higher in Pop II compared to HV. RT had significantly more Th2-like Treg in Pop II and III, and significantly less Th1/Th17-like Treg in Pop II and III compared to HV.

Conclusions: Whether shift in Th-like Treg is a consequence of immunosuppression or associated with tolerance requires further investigation.

EARLY EXPERIENCE WITH HYPOTHERMIC OXYGENATED MACHINE PERFUSION IN KIDNEY TRANSPLANTATION IN VICTORIA

DANIEL EZHILARASU STJ 1 , FURTADO R 1 , STEVEN M 1 , LEE D 1,2 , HE B 1,3 , WHITLAM J 1

1 Department of Nephrology, Austin Health, Victoria, 2 Department of Renal Medicine, Eastern Health, Victoria, 3 Department of Surgery, Austin. Health, Victoria

Aims: To report on the early experience of hypothermic oxygenated machine perfusion (HOMP) in kidney transplantation in Victoria, Australia.

Methods: We evaluated perfusion, donor and recipient parameters, along with post-transplant outcomes, for HOMP cases between August 2023 and January 2024.

Results: 14 deceased donor kidneys (5 DCD and 9 DBD) underwent HOMP, 10 via a “back-to-base” model. Median KDPI was 62 (IQR 23-73, max 90) and EPTS 76 (IQR 65-86, max 98). Four kidneys had significant donor acute kidney injury. Four kidneys underwent HOMP overnight for complexity/logistical reasons. Four kidneys were at risk of non-utilisation: two had non-utilisation of the contralateral kidney and two were declined by most centres. The median cold ischemia time (CIT) was 16 (IQR 13-22, max 26) hours, duration of HOMP was 9 (IQR 7-14, max 19) hours, and proportion of CIT perfused was 61% (IQR 55-72%). HOMP resistive index improved in all cases (start 0.42 (IQR 0.36-0.48) vs end 0.20 (IQR 0.16-0.24), p=0.001). Seven recipients received post-transplant dialysis (median duration 9, max 12 days). Two recipients developed rejection. All recipients are off dialysis. eGFR at 1 and 3 months was 36 (IQR 27-61) and 48 (IQR 41-66) ml/min/1.73m 2 , respectively. No machine-related issues were encountered. No complications were attributed to HOMP.

Conclusions: HOMP integrated well into transplant workflows. In addition to logistical benefits, HOMP supported transplantation of kidneys at risk of non-utilisation, raising the possibility of substantial cost offsets. Prioritising retrieval-commenced HOMP, instead of “back-to-base”, is needed to maximise the proportion of CIT on HOMP.

GENETIC TESTING SHOWS HIGH FREQUENCY OF MENDELIAN DISORDERS IN PAEDIATRIC KIDNEY TRANSPLANT RECIPIENTS

DESHPANDE A 1 , HOLMAN K 2 , HO G 2 , BENETT B 2 , KIM S 3 , MALLAWAARACHCHI A 4 , MCCARTHY H 5 , WANG YM 5 , TANUDISASTRO H 1 , ALEXANDER S 5

1 Centre for Kidney Research, University of Sydney, 2 Department of Molecular Genetics, The Children’s Hospital at Westmead, Sydney, 3 Department of Nephrology, The Children’s Hospital at Westmead, Sydney, 4 Department of Genetics, Royal Prince Alfred Hospital, Sydney, 5 Centre for Kidney Research, The Children’s Hospital at Westmead, Sydney,

Testing and identification of underlying genetic aetiologies of end stage renal failure in children has been improved with high throughput genetic testing and better testing for copy number variants.

Aim: To identify the genetic aetiology of end stage kidney failure in the paediatric kidney transplant population in a clinical cohort.

Methods: We reviewed the charts and genetic testing results of 128 children less than 18 years at the time of transplant who had received kidney transplants between 2009-2023 at the Children’s Hospital at Westmead.

Results: The clinical presentations included Congenital Abnormalities of Kidney and Urinary Tract (CAKUT) 32 patients, Nephrotic Syndrome (NS) 17 patients, polycystic kidney disease 11 patients, Tubular disorders 3 patients, Nephronophthisis 24 patients, glomerulonephritis 11 patients, VACTERL 4 patients and ESRF no obvious cause 2 patients, secondary ESRF in 12 patients including a number with Wilms tumours. Genetic causes were identified in 57 of them, including NPHS1, NPHS2, ADCK4, PLCE1 and TRPC6 in children with NS, NPHP1, NPHP3, NPHP4, NPHP18, CEP290, CEP164, INVS , WDR35, and OFD1 in patients with nephronophthisis, AGXT and CTNS in patients with hyperoxaluria and cystinosis and CAKUT related mutations including PAX2, GATA3, and a number of copy number variations including Chr 6 duplication, Trisomy 21, deletion in the 18p11.32 microdeletion region and chromosomal translocations.

Conclusions: A high rate of genetic disorders was found in paediatric kidney transplant recipients as the underlying cause of their kidney failure. These results may have important prognostic and clinical significance for them and their families.

THE ROLE OF TISSUE TYPING AND ANTIBODY ASSESSMENT IN FACILITATING AUSTRALIA’S FIRST UTERUS TRANSPLANT AND LIVE BIRTH

THAMOTHARAMPILLAI K 1 , GERSTL B 2 , KIELY N 2 , CHU G 1 , DEANS R 2

1 Transplantation Immunology Laboratory, Australian Red Cross Lifeblood, NSW 2 Royal Hospital for Women, NSW

Background: Women who experience uterine factor infertility (UFI) are unable to experience gestational parenthood and the condition affects 3-5% of the general population. Uterus transplantation provides an option for women to experience gestation, childbirth, and biological parenthood. In 2014, the world’s first successful uterus transplant was performed which resulted in a live birth in Sweden. Australia’s first successful uterus transplant at the Royal Hospital for Women, Sydney, culminated in a live birth in December 2023.

Methods: The first recipient in Australia to receive a uterus was a 30-year-old female, who underwent an emergency postpartum hysterectomy following complications from her initial pregnancy. Her mother served as the donor, with both recipient and donor were blood group compatible. The Australian Red Cross Lifeblood (ARCL) in New South Wales conducted comprehensive HLA typing and crossmatching. HLA typing was performed on recipient and donor using Next Generation Sequencing. HLA antibody testing was performed on the recipient’s serum using Luminex LABScreen TM technology. Additionally, flow cytometric crossmatches were performed using recipient’s serum against donor’s T and B cell lymphocytes.

Results: Recipient and donor were matched at one haplotype level for HLA with no detection of donor-specific antibodies (DSA) in the recipient’s serum. T and B cell flow crossmatches were negative. Post-transplant antibody testing was negative at 1 month, and the patient has ongoing monitoring for DSA.

Conclusions: HLA tissue typing is crucial in assessing compatibility and monitoring DSA, which contributed to successful transplant and delivery. Since then, further unrelated recipient and donor pairs have had histocompatibility assessment to facilitate transplantation.

FRAILTY PREDICTS UNPLANNED ADMISSIONS FOR LIVER TRANSPLANT CANDIDATES

JOHNSTON H 1 , ANDELKOVIC M 2 , MAYR H 3 , CHEN Y 4 , THRIFT A 4 , MACDONALD G 2 , HICKMAN I 5

1 Nutrition and Dietetics, Queensland Liver Transplant Service, Faculty of Medicine, Princess Alexandra Hospital, Brisbane, University of Queensland, 2 Gastroenterology and Hepatology, Queensland Liver Transplant Service, Princess Alexandra Hospital, Brisbane, 3 Nutrition and Dietetics, Centre for Functioning and Health Research, Faculty of Medicine, Princess Alexandra Hospital, Brisbane, University of Queensland, 4 Department of Medicine, Section of Epidemiology and Population Sciences, Baylor College of Medicine, 5 Nutrition and Dietetics, Faculty of Medicine, ULTRA Team, The UQ Clinical Trial Capability, Princess Alexandra Hospital, Brisbane, University of Queensland

Aims: Frailty is associated with mortality in liver transplant (LT) candidates, but the impact on morbidities is less clear. We investigated the impact of frailty (liver frailty index, LFI) on unplanned hospital admissions in this group.

Method: Between May 2018-September 2022 adults with cirrhosis being assessed for LT underwent frailty assessments during their initial dietitian appointment. Unplanned admissions were all admissions excluding booked surgeries/procedures (including paracentesis). Chi 2 /Mann-Whitney U tests, Kaplan-Meier and competing risk analysis were performed to explore associations between frailty and unplanned admissions.

Results: In 266 patients (75% male, median age 58 [IQR 50-63], median MELD 16 [11-19]), the median LFI was 3.7 [3.3-4.1]. 19% of patients were robust, 68% pre-frail, and 14% frail. The proportion of robust, pre-frail and frail patients with unplanned admissions was 9%, 71%, and 20% respectively, (p<0.001), over a median of 82.5 [IQR 29-160] days. Frail patients experienced unplanned admissions sooner than robust and pre-frail (p=0.00023, Figure 1). After adjusting for age, sex, hepatocellular carcinoma presence, and MELD score, LFI was independently associated with higher risk of unplanned admissions. For every point increase in the LFI, there was a 48% increased risk of unplanned admissions (HR: 1.481, 95% CI: 1.035-2.120, p=0.032). Each point increase in the MELD was associated with an 11% increase in unplanned admission risk (HR: 1.106, 95% CI: 1.063-1.152, p<0.001).

Conclusion: Frailty is associated with an increased risk of unplanned admissions for LT candidates. Early routine assessment of frailty during LT evaluation should be considered to identify patients at greatest risk.

Figure 1

Kaplan-Meier Curves of unplanned admissions by LFI at first assessment (robust, pre-frail, frail)

CARBAPENEMASE- PRODUCING ENTEROBACTERALES (CPE): AN INCREASING THREAT TO AUSTRALIAN LIVER TRANSPLANT RECIPIENTS

KAMALADASA D 1 , LIU K 1 , DOLAN L 2 , VAN HAL S 3 , LEE A 3 , MARINELLI T 3

1 AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, NSW, 2 Infection Prevention and Control Unit, Royal Prince Alfred Hospital, NSW, 3 Department of Infectious Diseases and Microbiology, Royal Prince Alfred Hospital, NSW

Introduction Multidrug-resistant organisms, including carbapenemase-producing Enterobacterales (CPE) are associated with high morbidity and mortality in liver transplant recipients (LTRs). In Australia, there is a paucity of data regarding CPE in LTRs, who are at increased risk for both CPE colonization and infection.

Methods: Single-center, retrospective cohort study of CPE in LTRs January 2015 to August 2023. LTRs are routinely screened for CPE in intensive care unit, with further targeted screening based on epidemiologic risk. All CPE isolates undergo whole genome sequencing (WGS). CPE cases were identified using the WGS database, classified as colonization or infection, and analyzed using descriptive statistics.

Results: There were 28 episodes of CPE isolation from 24 LTRs. Using standard definitions, 5 and 23 cases were community and healthcare-acquired, respectively. Ten episodes of CPE infection, involving the urinary tract (N=4, 40%), bloodstream (N=3, 30%), wound/abscess (N=2, 20%) and gastroenteritis (N=1, 10%) were found. The remaining 18 cases represented CPE colonization. Klebsiella pneumoniae was the most common CPE-harboring bacterial species (N= 12, 42.9%) with the New-Delhi metallo-β-lactamase (N=13, 46.4%) the most common CPE gene detected. CPE cases increased over time (Figure 1) from 5.1 to 12.2 per 10, 000 occupied bed days (OBDs). The overall rate of CPE was significantly greater in LTRs than the general hospital population (6.24 vs 0.95 cases per 10,000 OBDs; p=0.0075). Two patients (20%) died within 30 days of CPE infection diagnosis.

Conclusion: Infection with CPE is an emerging risk for Australian LTRs. Further research is required to determine optimum treatment and prevention.

Figure 1: CPE colonization and infection in liver transplant recipients

PREGNANCY AFTER KIDNEY TRANSPLANTATION: GLOBAL INSIGHTS BASED ON REGISTRY DATA FROM THREE CONTINENTS

GIAPOUTZIDOU S 1 , HEWAWASAM E 2 , COSCIA L 3 , DE JONG M 1 , JESUDASON S 4

1 Groningen Kidney Center (GKC), University Medical Centre Groningen, Netherlands, 2 ANZDATA, South Australia, 3 Transplant Pregnancy Registry International, Gift of Life Institute, Philadelphia, USA, 4 Central Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital

Aim: Limited cross-cultural data exists on pregnancy after kidney transplantation. We compared approaches to data capture and basic outcomes of pregnancies in female kidney transplant recipients (KTR) across three continents.

Methods: Data was extracted from annual reports, publications and directly from the Pregnancy After Renal Transplantation OUTcomes registry (PARTOUT, Netherlands), Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) and Transplant Pregnancy Registry International (TPRI, United States and international).

Results: Each registry applied different methodologies for case capture. PARTOUT identified all pregnant KTR (1971-2017) across The Netherlands via the National Organ Transplant Registry and health professional consultation, conducting a once-off, highly granular retrospective medical record review. ANZDATA conducts annual surveys on all KTR, with pregnancy events voluntarily reported since inception and formally since 2001 via paper surveys or online, with expansion of data items in 2018. TPRI registration is voluntary via health providers or patient self-enrolment. Interviews with KTR occur at enrollment, after delivery and then every two years. Characteristics and basic outcomes are shown in Table 1.

Conclusions : Basic pregnancy outcomes in KTR were consistent across 3 registries, demonstrating pregnancy in female KTR can be successful but remains higher-risk. Understanding registry strengths and biases is essential when comparing outcomes across countries; sustainability of data collections remains a challenge. The development of global minimum datasets with shared definitions may increase the power to monitor trends and identify drivers of adverse outcomes in this high risk cohort of women.

Table 1: Characteristics of pregnancy, fetal and transplant outcomes from three registries.

SEX DIFFERENCES IN HOSPITAL UTILISATION AFTER LIVING KIDNEY DONATION

COHEN A 1 , WYBURN K 1 , DE LA MATA N 2 , WEBSTER A 3 , SINGLA A 4 , WYLD M 3

1 Renal and Transplantation Unit, Royal Prince Alfred Hospital, Sydney, 2 School of Public Health, University of Sydney, 3 Renal and Transplantation Unit, Westmead Hospital, Sydney, 4 Vascular Surgery, North Shore Private Hospital, NSW

Aims: While kidney donors have comparable mortality compared to the general population, there is paucity of data evaluating health service utilisation after kidney donation. We aimed to evaluate the index admission length, presentations to emergency departments (ED), and hospital admissions in the 12 months following donation, with a focus on sex differences.

Methods: A population-based cohort study of NSW living kidney donors 2004-2019 using the Safety and Biovigilance in Organ Donation (SAFEBOD) dataset, which linked donors to administrative health databases. We estimated ED presentations and hospital admissions (excluding pregnancy-related admissions) standardised incidence ratios (SIR) compared to general population.

Results: Of 1426 living kidney donors, 812 (56.9%) were female and 614 (43.1%) male. Median length of stay for the donation admission was 4 days (IQR 4-5days) with no difference by sex (p=0.31). Compared to the general population, excess hospital utilisation was significant in the first month after donation (figure 1). In the first month, there were fewer excess ED presentations in females compared to males (SIR2.55 (95%CI 1.85-3.50) vs. 3.60(2.68-4.84), p<0.01). There was no difference by sex in hospital admissions (females SIR 1.82(1.45-2.27) vs. males 1.54(1.16-2.04), p=0.13).. By 12 months, the rate of excess ED presentations was not statistically different between females and males. At 12 months, there was a trend towards fewer hospital admissions compared to the general population, with no difference between sexes (SIR0.95(0.83-1.08) vs. 0.90(0.77-1.05) respectively (p=0.64)).

Conclusion: This study demonstrates significantly increased ED presentations and hospital admissions in the first month after donation for males and females.

Figure 1: Standardised incidence ratio for (A) ED presentations and (B) Hospital admissions, by sex and time after donation

SEX DIFFERENCES IN RELATIVE CANCER SURVIVAL IN KIDNEY TRANSPLANT RECIPIENTS: A BI-NATIONAL STUDY, 1980-2019

ROSALES BM 1 , OLIVERAS-PAGES L 2 , LEES J 3 , DE LA MATA N 1 , WEBSTER AC 1

1 School of Public Health, University of Sydney, 2 Department of Nephrology, Hospital Universitari de Bellvitge, Spain, 3 School of Cardiovascular and Metabolic Health, University of Glasgow

Aims: We sought to estimate the relative cancer survival in kidney transplant recipients and describe differences in trends between males and females.

Methods: We took all kidney transplant recipients with de-novo cancer and compared survival with the general population with cancer in Australia and New Zealand 1980-2019. Relative survival ratios (RSR) post-cancer diagnosis were estimated using the general population as the reference group, matched for sex, age, calendar year and country. Excess mortality ratios (EMR) were estimated using Poisson regression.

Results: There were 1,899 deaths in 3,253 kidney transplant recipients with de novo cancer in the cohort, 1,947 (60%) males and 1,306 (40%) females. Median follow-up was 14 years from the first transplant and 3.3 years from the first cancer diagnosis. In the general population with cancer, females experienced better relative cancer survival compared to males (Five-year RST 0.71 [95%CI:0.71-0.72] vs 0.63 [95%CI:0.63-0.63] respectively). Similarly, female kidney transplant recipients experienced better relative cancer survival compared to males (five-year RSR 0.59 [95%CI:0.56-0.62] vs 0.53 [95%CI:0.50-0.55] respectively). Excess mortality was 41% (adjusted EMR 1.41 [95%CI:1.30-1.54]) higher in female kidney transplant recipients with cancer than females in the general population with cancer and 26% higher in male recipients (adjusted EMR 1.26 [95%CI:1.18-1.36]) than males in the general population with cancer. Excess mortality has increased at a steeper rate in female recipients compared to male recipients in the past 30 years (Figure 1, p<0.001).

Conclusions: Female kidney transplant recipients with cancer had better relative survival than males but experienced higher survival deficits (excess mortality ratio) when compared with the general population with cancer.

Figure 1: Relative survival ratio (RSR) post-cancer diagnosis stratified in a) males and b) females over calendar years (5-year groups) in the general population, kidney transplant recipients and dialysis patients. The reference population is the overall general population of Australia and New Zealand (RSR=1).

SEX DIFFERENCES IN CARDIOVASCULAR RISK AND KIDNEY FUNCTION: SERUM CREATININE VERSUS CYSTATIN C

DE LA MATA N 1 , LEES J 2 , HEDLEY J 1 , SULLIVAN M 2 , ROSALES B 1 , MARK P 2 , WEBSTER A 1

1 Collaborative Centre for Organ Donation Evidence (CODE), Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, 2 Institute of Cardiovascular and Medical Sciences, University of Glasgow

Background: Risk of cardiovascular events increases as kidney function declines, and males have higher risk than females. It is unclear whether this sex difference persists at all stages of kidney disease, or with different biomarkers of kidney function.

Aims: To compare risk of cardiovascular events/death by sex and kidney function.

Methods: We used data from the UK Biobank, a prospective cohort aged 40-69 in 2006-2010. We calculated eGFR using serum creatinine, cystatin C, or both. Cardiovascular events were arrythmia, heart failure, and ischaemic heart disease. We modelled time to first event and death using Cox regression, adjusted for age, smoking, diabetes, cancer, hypertension, hyperlipidaemia, total:HDL cholesterol, and blood pressure. We repeated this for each eGFR measure. All models included a sex-eGFR interaction.

Results: Among 503,325 participants, N=394,920 (78%) had no prior cardiovascular events and sufficient data for analysis (55% female). At normal kidney function (creatinine eGFR 90-104mL/min/1.73m 2 ), females had lower risk of cardiovascular events (HR 0.60, 95%CI 0.59-0.62) and death (HR 0.41, 95%CI 0.36-0.46). This advantage disappeared as kidney function declined. Females approaching dialysis or transplant (creatinine eGFR<30) had similar risk to males for cardiovascular events (HR 0.81, 95%CI 0.57-1.15, interaction p=0.007) and death (HR 1.19, 95%CI 0.62-2.30, interaction p=0.06). The sex-eGFR interaction was more apparent using cystatin C, and creatinine+cystatin C (all interaction p<0.001).

Conclusion: Females experience a steeper increase than males in risk of cardiovascular events/death as kidney function declines, which has implications for people progressing towards dialysis or transplant. Using creatinine eGFR only may obscure this effect.

Figure 1: Forest plots of adjusted hazard ratios for cardiovascular events by sex and eGFR

THE IMPACT OF ISCHAEMIC TYPE BILIARY LESIONS ON HEALTH UTILITY AFTER DCD LIVER TRANSPLANTATION

HALLE-SMITH J 1 , BURAK M 1 , CLARKE G 1 , HANN A 2 , SUTHANANTHAN A 1 , ROBERTS K 1

1 Liver Unit, Queen Elizabeth Hospital Birmingham, UK, 2 University of Birmingham, UK

Aims: To investigate the cost of ITBL to the health service so that potential savings with new technology could be explored.

Methods: Consecutive DCD liver transplants between 2016-2018 were reviewed from our institutional database. To compare healthcare costs between patients who developed ITBL and the standard DCD cohort, ITBL patients were matched to patients who received a DCD static cold storage (SCS) graft during the same period. Matching was based on age, indication for transplant and UKELD at listing. For ITBL and matched patients, all hospital episodes after discharge from index transplant were reviewed. Cost codes for each procedure or episode were obtained from the NHS tariffs.

Results: There were 115 patients included in the study, of which 19 developed ITBL (16.5%). Graft survival was significantly lower in the ITBL group (23.4 months vs. 72.8 months; p=0.001), with 9 (47%) of the patients requiring retransplantation. Matching of the ITBL and DCD SCS controls was satisfactory on the specified parameters. The total hospital costs were significantly higher amongst the ITBL group, with an average cost per patient of £97,304 (£3,116-£271,278) compared to £16,802 (£3,982 - £93,171) in the matched control group.

Conclusions: The development of ITBL after DCD liver transplantation leads to significantly increased healthcare costs compared to matched DCD SCS controls. These costs should be taken into account by health service providers when deciding whether to fund technologies that may reduce the ITBL rate in DCD grafts, such as NRP and HOPE.

Figures 1a and 1b – plots to visualise readmission bed days and treatment costs for ITBL and matched no ITBL patients after DCD liver transplant .

THE EVOLUTION OF LATE LIVER RETRANSPLANTATION

HANN A , NUTU A, LEMBACH H, ALFARAH J, CAINE G, SANABRIA-MATEOS R, DASARI B, OO Y, ARMSTRONG M, BARTLETT D, FERGUSON J, MURPHY N, BENNETT D, RAJORIYA N, ISAAC JL, MIRZA D, ROBERTS K, ISAAC JR, TRIPATHI D, PERERA T

The Liver Unit, Queen Elizabeth Hospital, Birmingham UK

Background: Liver re-transplantation is indicated following late graft failure, however reported outcomes are inferior to primary transplant. Our aim was to describe how the practice and outcomes of late retransplant have evolved over the last 15 years. and factors associated with poor outcomes.

Methods : A single-centre retrospective study of patients that underwent late liver retransplant (>21days) with a graft from a deceased donor between 2007-2021. The study period was divided into three eras (Era 1:2007-2011, Era 2:2012-2016, Era 3:2017-2021). Recipients were classified as benchmark or high-risk, based on published benchmarking criteria. Patients with PVT, MELD ≥25, pre-transplant mechanical ventilation, receiving a DCD graft or undergoing repeat retransplant were considered high risk. The primary outcome was 1-year graft and patient survival. A multivariate analysis was performed to identify factors associated with graft loss within 1-year.

Results: Among 153 late retransplants, 1-year graft and patient survival was 133/153 (87%) and 121/135 (90%) respectively. Overall, 1-year patient survival has increased from 17/20 (85%) in era-1 to 67/74 (91%) in era-3 (Log rank p=0.08). Figure A&B demonstrates graft survival for benchmark recipients by era. Patient survival for benchmark retransplants improved over the 3 eras [Era-1:9/11(82%) vs. Era-2:24/28(86%) vs. Era-3:45/46(98%); p=0.01 (log rank)] (Figure 1B), but not in high-risk retransplants. (Figure C&D). On multivariate analysis, split grafts (OR: 9.99, 95% CI: 2.02-49.46, P =0.005) and portal vein conduits (OR: 5.480, 95% CI:1.657-18.130, P =0.005) were associated with graft loss at 1-year.

Conclusion: Excellent graft and patient survival can be achieved with late retransplant in the modern era.

Legend: Survival with grouping based on risk (A&B), Benchmark retransplants stratified by era (C&D), High risk transplants stratified by era (E&F).

30 YEARS OF HISTORY, EVOLUTION, AND SURGICAL OUTCOMES OF PANCREAS TRANSPLANTS IN A SINGLE AUSTRALIAN CENTRE

SOON D 1 , CHUNG D 2 , YII M 3 , THWAITES S 3 , BELL R 3 , SAUNDER A 3

1 National Pancreas Transplant Unit, Monash Medical Centre, Melbourne, 2 Renal Transplant Unit, Monash Medical Centre, Melbourne, 3 Department of Vascular and Transplantation Surgery, Monash Medical Centre, Melbourne

Background: Pancreas transplants were performed successfully in 1966 1 at the University of Minnesota. The first pancreas transplant in Australia was performed in Monash National Pancreas transplant unit (NPTU). Currently Monash national pancreatic transplant center performs a third of Australia’s pancreas transplants. The aim is to determine the evolution of surgical technique, explore and understand the rationale behind the change, as well as outcomes related to surgical technique of pancreatic transplants throughout the development of the national transplant program.

Methods: Retrospective analysis of all pancreatic transplants done from 1984 to 2022.

All types of pancreatic transplants will be included (Simultaneous pancreas and kidney transplants (SPK), Pancreas after kidney (PAK), Pancreas transplants alone (PTA)) Demographic data collected include recipient age and gender. Immunosuppression regimen including induction immunosuppression and maintenance were also collected.

Surgical technique, Portal or systemic, exocrine drainage Bowel or bladder and cases that were converted to enteric from bladder drainage were also collected for the study.

Outcomes that were collected include graft associated complications such as graft thrombosis rate and ultimately, pancreas graft survival rate and length of Stay. The data were divided into two different periods to reflect the potential differences and evolution throughout the years, namely the initial period from 1984 to 2001, and the subsequent 20 years from 2002 to 2022.

Results: 48 pancreatic transplants were done from 1984 to 2001, following that from 2002 to 2022 that number increased to 236 transplants in total. Surgical technique including pancreatic drainage have evolved from Bladder to enteric drainage. Venous drainage on the other hand have evolved from systemic to portal and currently back to systemic drainage. The rate of Early pancreatic allograft thrombosis (EPAT) in the institution was 20%(CIV), 23%(EIV) and 14%(SMV) from 1984-2001 and subsequently reduced to 5.9%(IVC), 23.3%(CIV), 26.1%(EIV), 13.3% (SMV) after altering the surgical technique. The average length of stay of patients in the first cohort from 1984 to 2001 was 18.1 days and the subsequent length of stay for patients from 2002 to 2022 was 15.5 days. Finally, pancreatic graft survival rates were 75.05% 1-year graft survival and 55.55 5-year graft survival from 1984 to 2001 and 93.5% 1-year graft survival and 80.6% 5-year graft survival from 2002-2022.

Conclusion: Pancreatic transplants are medically complex and technically demanding procedures that should be done within a specialized unit. With over 30 years of experience, it is important for every patient to have good pre-operative workup with the involvement of a multidisciplinary team, meticulous intra-operative tissue handling and stringent post operative care to achieve the best outcomes for the patient.

Improved recovery of rat hearts after cold storage by acid sensing ION channel inhibitor Hi1a varies with preservation solution

DUTTA S 1,2,3 , GAO L 4 , DOYLE A 4 , PALPANT N 5 , KING G 5 , MACDONALD P 2,3,4 , VILLANUEVA J 1,2

1 Transplantation Laboratory, Victor Chang Cardiac Research Institute, Sydney, 2 St Vincent’s Clinical School, The University of New South Wales, 3 Department of Heart and Lung Transplantation, St Vincent’s Hospital Sydney, 4 Transplantation Laboratory, Victor Chang Cardiac Research Institute, Sydney, 5 Institute for Molecular Bioscience, The University of Queensland, Infensa Bioscience Pty Ltd.

Aims: Most heart transplantations rely on cardioplegia solution and cold static storage (CSS) for organ preservation, however long ischaemic times result in poor outcomes. ASIC1a inhibitors have shown promise to reduce ischaemia-reperfusion injury. We investigated the impact of supplementation of cardioplegia with the ASIC1a inhibitor Hi1a on cardiac function following CSS.

Methods: Hearts were isolated from male Wistar rats (348-463g, n = 4-8/group), perfused ex-vivo with Krebs-Henseleit buffer at 37°C, and baseline haemodynamic measurements of aortic flow (AF) were obtained. Hearts were arrested with St Thomas’s (STH), Celsior (Cel) or Custodiol (Cus) cardioplegia either alone, supplemented with 10nM Hi1a or 50nM Hi1a. Following 6-hour CSS (4°C), hearts were re-perfused ex-vivo. Haemodynamic measurements were obtained, and recovery expressed as percentage of pre-storage baseline (mean ± SEM).

Results: As shown in Figure 1, compared to unsupplemented Celsior (AF 14±5.0%) hearts stored in Celsior supplemented with either 10nM Hi1a (AF 54±12%, P = 0.028) or 50nM Hi1a (65±6.7%, P < 0.001) showed significantly improved recovery in a dose-dependent manner. Hearts stored in Custodiol trended towards worse recovery when supplemented with both 10nM and 50nM Hi1a. Hearts stored in STH had poor recovery of AF, with and without supplementation.

Conclusions: Supplementation of Celsior with Hi1a showed improved cardiac function after 6 hours cold ischaemic storage, showing benefit as a preconditioning agent. Further work is needed to examine reasons for differing efficacy in different cardioplegia solutions. ASIC1a inhibitors may improve acceptable ischaemic times for organ transplantation however compatibility with various cardioplegia solutions should be considered.

Figure 1: Mean myocardial functional recovery following 6hrs CSS, expressed as a percentage of baseline aortic flow. Error bar represents standard error of the mean.

TRANSCRIPTOMICS CHANGES AS A MARKER OF LIVER TRANSPLANT VIABILITY DURING NORMOTHERMIC PERFUSION

SOLAL C 1 , REILING J 2 , SHAH S 1

1 Institute for Molecular Biosciences, University of Queensland, 2 Princess Alexandra Hospital, Brisbane

Background and Aim: Normothermic machine perfusion, an alternative organ preservation method, has, over the last few years, increased the utility rate of marginal donor livers worldwide. Currently, empirically defined perfusion and biochemical criteria are used to determine graft viability during NMP. However, a greater understanding of the changes occurring during NMP is required to validate those parameters. In this study, we investigate transcriptomic changes observed within viable and non-viable livers.

Methods: For 14 livers included in this study, biopsies were collected at the start and end of cold ischemic time as well as after 3 and 6 hours of perfusion. Biopsies were then used to generate RNA-sequencing data. Liver undergoing NMP were stratified based on currently accepted viability criteria (lactate clearance, glucose usage…) and used to investigate molecular changes occurring during perfusion. Differentially expressed genes analysis was then performed to compare each viability group to cold ischemic time while accounting for the longitudinal aspect of the data collection.

Results: An active transcriptome was identified within viable livers (2413 DEGs), while non-viable livers displayed a comparatively inert transcriptome (572 DEGs). While all viable livers passed the currently defined viability criteria, one liver transcriptome behaved identically to non-viable livers, highlighting that gene expression characterises a different aspect of viability during normothermic perfusion. Finally, gene expression was successfully used to predict liver viability within an out-of-sample cohort.

Conclusion: This study highlights that gene expression can be used to stratify the liver undergoing NMP and should be investigated as a potential addition to the currently defined viability criteria.

NEPHROLOGIST VIEWS ON DECEASED DONOR KIDNEY TRANSPLANT OFFER PROCESSES: A QUALITATIVE STUDY

WEIGHTMAN A 1 , DUNCANSON E 2 , COGHLAN S 3 , CLAYTON P 2

1 School of Medicine, University of Adelaide, 2 ANZDATA, South Australia, 3 School of Computing and Information Systems, University of Melbourne

Background: Assessment of kidney transplant offers can be difficult, requiring a nuanced consideration of the specific risks and benefits for the recipient. To date, there has been limited research into this decision-making process from the perspective of the doctors involved.

Aims: To explore the experiences and considerations of nephrologists at the time of deceased donor kidney transplant offers.

Methods: Semi-structured interviews were conducted with 14 nephrologists from five hospitals across South Australia and the Northern Territory. Transcripts underwent thematic analysis.

Results: Four key themes were identified: necessity of trust (including subthemes of faith in the system, decision making as a team and sharing the journey with the patient), good enough offers (pragmatism as an asset, balancing competing risks, acceptance of uncertainty), value based tensions (respecting patient autonomy, protecting donors and their families, awareness of social justice obligations) and doctor as the ultimate decision maker (burden of decision making, the art of transplant medicine, preparation as an essential part of the offer process).

Conclusion: Nephrologists are keenly aware of the many competing interests to be balanced at the time of kidney transplant offer and are comfortable with their role as principal decision maker in this process. However, they were less clear about the ideal level of patient involvement in this process, with many nephrologists identifying the tension between respecting patient autonomy and ensuring optimal patient outcomes, at an individual and societal level. The study demonstrates a need for further research to explore these issues from the patient perspective.

INSIGHTS FROM INTEGRATED MULTIOMICS SHOW SPONTANEOUS LIVER DEFATTING DURING LONG-TERM NORMOTHERMIC MACHINE PERFUSION

NIU A , HUANG J, LAU N, LY M, BABEKUHL D, RISBEY C, YOUSIF P, DENNIS C, LIU, MCKENZIE C, KENCH J, MCCAUGHAN G, CRAWFORD M, PULITANO C

Department of Transplant Surgery, Royal Prince Alfred Hospital, Sydney

Background: Experimental studies have demonstrated defatting of steatotic livers during ex-situ long-term normothermic machine perfusion (LT-NMP) with the use of pharmacological cocktails. However the impact of isolated LT-NMP and qualitative changes in lipid species remains yet to be clarified. This study aims to employ a multiomics approach to evaluate the changes in lipid profiles that occur in human livers perfused on LT-NMP for >1 week.

Methods: Twenty partial human liver grafts were perfused using a modified red cell-based NMP system, consisting of a dialysis filter, oxygenator and infusions to allow for extended ex-situ survival. Liver viability was demonstrated through vascular haemodynamics, lactate clearance, glucose metabolism and bile production. Microvesicular (MiS) and macrovesicular (MaS) steatosis was determined on histopathology. A multiomics approach including lipidomics, metabolomics and next generation sequencing was used to identify key molecular pathways associated with defatting.

Results: Fourteen initially steatotic grafts on histopathology were included. The average perfusion time was 6.4 days, during which 6/8 (75%) grafts showed a reduction in MaS, whilst 8/14 (57%) showed a reduction in MiS. The majority achieved defatting after a perfusion of 3 days. Lipidomic analysis demonstrated a reduction in short chain saturated and monosaturated fatty acids, whilst triglycerides and polyunsaturated fatty acids tended to accumulate.

Conclusion: We demonstrate that LT-NMP can spontaneously reduce the steatotic content of fatty livers, without needing additional defatting agents. Studies of human liver defatting on LT-NMP should focus not only on the change in quantity but also quality of lipids, including presence of toxic lipid species.

TREATMENT WITH A SPECIFIC INHIBITOR OF THE COMPLEMENT LECTIN PATHWAY PROTECTS AGAINST RENAL ISCHEMIA-REPERFUSION INJURY IN MICE

BONGONI A 1 , MCRAE J 1 , SALVARIS E 1 , FISICARO N 1 , KISS B 2 , PÁL G 2 , GÁL P 2 , COWAN P 1,3

1 Immunology Research Centre, St Vincent’s Hospital Melbourne, 2 Department of Biochemistry, Eötvös Loránd University Budapest-Hungary, EvolVeritas Biotechnology Ltd, 3 Department of Medicine, St Vincent’s Hospital Melbourne, University of Melbourne

Background: Complement is a potent mediator of ischemia-reperfusion injury (IRI), which significantly affects function and survival of transplanted kidneys. Complement is activated by the classical, alternative and lectin pathways. Mannan-binding lectin–associated serine proteinase (MASP)-2 is essential for lectin pathway activation, which contributes to IRI and is a potential drug target. We constructed a stable homodimer EVO24L comprising a MASP-2 inhibitor recombinantly fused to a human IgG Fc.

Aims : To test EVO24L for the suppression of complement-mediated IR-induced organ damage in a mouse model of renal IRI.

Methods : 10-12 week-old male C57BL/6 mice were subjected to right nephrectomy and left renal ischemia for 22 min (IRI), or nephrectomy only (Sham). Mice (n=8/group) were treated with 2x EVO24L or vehicle control: i.p. 2 h pre-ischemia (600 mg/kg) and i.v. immediately post-reperfusion (300 mg/kg). Mice were euthanized 24 hr post-reperfusion, and serum and plasma samples were collected to assess renal function (creatinine, urea) and complement activation (C5a). Kidneys were harvested to analyse histopathology (tubular injury), complement C9 deposition and immune cell infiltration.

Results : Compared to Sham, severe renal injury was induced following IR in vehicle-treated mice as indicated by significantly increased creatinine and urea, C5a, tubular injury, C9 deposition, and cellular infiltration. EVO24L treatment protected against IR-induced damage, with significantly lowered renal dysfunction, tubular injury, complement activation and cell infiltration.

Conclusion : Complement lectin pathway inhibition using EVO24L protected against kidney IRI. Blockade of lectin pathway activation by EVO24L is thus a promising therapeutic approach to reduce IRI and improve organ transplant function.

RENAL OUTCOMES OF NRP-DCD RECIPIENTS IN THE IMMEDIATE POST-OPERATIVE PERIOD: A COMPARISON WITH MATCHED DCD-SCS RECIPIENTS

CLARKE G, HALLE-SMITH J, MANGCO J, PAPAMICHAIL M, RAZA S, NUTU A, SANABRIA-MATEOS R, DASARI B, BARTLETT D, PERERA T, ROBERTS K, MERGENTAL H, SUTHANANTHAN A

Liver Surgery Unit, Queen Elizabeth Hospital Birmingham, UK

Introduction: Normothermic regional perfusion (NRP) is a novel technique of organ recovery and assessment following circulatory death (DCD). Whilst renal dysfunction is more prevalent following DCD liver transplantation, we postulate this is mitigated following NRP-DCD. We investigated the effects of DCD-NRP on patients renal function in the immediate post-operative period.

Methods: A retrospective cohort study was performed for all patients who underwent DCD-NRP liver transplantation at Queen Elizabeth Hospital Birmingham between January 2022 and January 2024. DCD-NRP recipients were 2:1 matched with DCD-SCS recipients between 2010–2020. Recipients were matched with regard to the UK DCD risk score. Donor and recipient risk factors, and recipient renal and liver biochemistry were collected.

Results: Eighteen patients received a DCD-NRP liver transplant, matched to 36 patients receiving DCD-SCS organ. In the DCD-NRP cohort, there was 100% graft and patient survival, with no incidence of ischaemic cholangiopathy. DCD-NRP cohort had a reduced peak creatinine (145% vs. 162%, p=0.0071) and reduced GFR change (-26% vs. -29%, p=0.0151), with corresponding reduction in rates of acute kidney injury (Figure 1). Median MEAF score in DCD-NRP cohort was also reduced (3.5 vs. 3.9, p=0.5).

Discussion: In our early experience, we found that patients who received DCD-NRP organs had a reduced renal hit compared to DCD-SCS recipients. Whilst there is a trend towards a reduced MEAF score in DCD-NRP recipients, further numbers will be required to assess this further. NRP remains a powerful technique in assessing and optimising DCD livers, allowing safe expansion of the donor pool.

Figure 1

SHORT COURSE TOTAL LYMPHOID IRRADIATION POST HEART TRANSPLANT FOR RECALCITRANT REJECTION – A SINGLE CENTRE EXPERIENCE

LEE F 1 , FAZACKERLEY C 1 , KIRUPANANTHER H 2 , VAZ C 2 , TRUONG L 3 , DOWNING J 3 , D’ORSOGNA L 4 , LIM T 5 , SHAH A 1 , LAM K 1

1 Advanced Heart Failure and Transplant Unit, Fiona Stanley Hospital, Perth, 2 Radiation Oncology, Sir Charles Gairdner Hospital, Perth, 3 Pathwest, Fiona Stanley Hospital, Perth, 4 Department of Clinical Immunology, Fiona Stanley Hospital, Perth, 5 Radiation Oncology, Fiona Stanley Hospital, Perth

Aims: A retrospective review of patients who received a short course of total lymphoid irradiation (TLI) post heart transplantation (HTx) for refractory cardiac rejection in Western Australia.

Methods: Information was obtained from electronic medical records and the transplant database.

Results: From 2001-2023, 21 HTx recipients (mean age ± std 44.2±12.8 years; 47.6% female) received TLI. Five patients were highly sensitized pre-HTx (calculated panel-reactive antibody >80%). Eleven patients had a left ventricular assist device pre-HTx. Induction immunosuppression (n=12), which only became routine in the post-2010 era, comprised of basiliximab or antithymocyte globulin. Maintenance immunosuppression mostly consisted of mycophenolate, prednisolone and a calcineurin inhibitor. Other immunotherapy included plasmapheresis (n=11), intravenous immunoglobulin (n=6), and rituximab (n=8). Patients received 4.5Gy of TLI in four fractions over 4 consecutive days (median of 178 days post-cardiac transplant; IQR 44-914 days). TLI was well tolerated with no persistent lymphopenias. Eleven patients had no significant cellular or antibody mediated rejection detected post TLI (median follow-up 407 [IQR 190-2414] days). Thirteen patients, all transplanted pre-2010, have since deceased (median graft survival 11.9 [IQR 4.8-12.1] years, mean follow-up 8.2 years). One patient died of metastatic colon cancer. Two patients received a second TLI course and both patients underwent re-HTx for graft dysfunction.

Conclusions: We report the largest case series of patients in Australia who received TLI post HTx. Short-course TLI is well tolerated, and an alternative option for patients with cardiac rejection refractory to routine immunotherapy. Further studies are required to assess the longer-term efficacy of this treatment.

GIVING YOUNG PEOPLE THE RESOURCES THEY NEED TO MAKE DECISIONS SURROUNDING ORGAN AND TISSUE DONATION

HUUSKES B 1 , HOKKE S 2 , ARTS D 1

1 Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Victoria, 2 Judith Lumley Centre, La Trobe University, Victoria

Aims : Develop and disseminate education videos addressing young peoples’ knowledge gaps surrounding organ donation.

Methods: Thematic analysis of focus groups with young people was performed in 2022. This identified both knowledge gaps young people had, and preferences on organ and tissue donation messaging.

Results: Nine short educational videos were produced in consultation with a youth working group. A young transplant recipient within the target demographic hosted the videos covering topics including; what is organ and tissue donation, what is the register, how to register, myths and the importance of conversations. Additional interview style videos were made sharing the stories of a young donor family and transplant recipient. In collaboration with a university media team, a campaign was created to disseminate these resources through university social media channels and displayed call to action graphics digital screens across 5 regional and metropolitan campuses. Ten days into the 40 day campaign, over 58,500 people were reached and over 1,200 have clicked through to “learn more.” After the campaign, metrics including number of people reached, click through rate, video website visits and video views will be reported. The number of people who register directly on the DonateLife website throughout this campaign will also be reported.

Conclusion: The generation of educational resources informed by research on young people may fill the knowledge gaps young people have about organ and tissue donation. University partnership allows campaigns to be targeted to where young people visit frequently, increasing the awareness and promoting discussions surrounding organ and tissue donation.

INFECTION TRANSMISSION RISK FROM KIDNEY DONORS WITH ACTIVE HEPATITIS B: A SYSTEMATIC REVIEW AND META ANALYSIS OF OBSERVATIONAL DATA

WALLER K , DAVIES R, GARRETT E, HEDLEY J, WYBURN K, WEBSTER A

1 Centre for Organ Donation Evidence (CODE), University of Sydney

Aims: Potential kidney donors with active hepatitis B (HBV), defined as positive surface antigen (HBsAg) and/or nucleic acid test (NAT), are usually declined for HBsAg-negative recipients. With vaccination and antivirals, transplantation could be safe. We aimed to quantify the transmission risk.

Methods: Systematic review and meta-analysis, searching MEDLINE for “hepatitis B” and “kidney transplantation”. We included cohorts of kidney transplantation from donors with active HBV to HBsAg-negative recipients. Transmission was defined as HBsAg or HBV NAT positivity post-transplant. Transmission proportions were pooled using meta-analysis with random effects, employing Freeman-Turkey double arcsine transformation and exact 95% confidence intervals.

Results: After screening 3,143 records, 21 cohorts were included. Among 606 donors, most were living (57%); all had positive HBsAg but most had negative NAT (55%). Among 614 recipients, most had protective surface antibody (HbsAb, 86%) titres, and many were core antibody positive (48%). Prophylaxis varied in strategy (8 cohorts universal, 6 none), type (hepatitis B immunoglobulin 37% recipients, antivirals 44%) and duration. There were 26/614 HBV transmissions (4.2%), fewer where all recipients had protective HBsAb (1.3%) or all donors had negative NAT (0.6%). There were 2 deaths due to HBV (0.3%): both occurred off prophylaxis (one never given, one post short course). The pooled transmission rate was 0.8% (95%CI: 0.00-3.8%, Figure 1) although there was substantial heterogeneity between studies (I 2 =53.9%). This may be explained by differences in case ascertainment, prophylaxis or donor/recipient factors.

Conclusion: Given low transmission rates, donation could be considered from kidney donors with active hepatitis B in controlled circumstances.

Figure 1: Forest plot of HBV transmissions from observational studies of donors with active HBV to susceptible recipients

PRE-TRANSPLANT ANGIOTENSIN TYPE I RECEPTOR ANTIBODIES ARE ASSOCIATED WITH ACUTE KIDNEY INJURY POST-LUNG TRANSPLANT

DARIE A 1 , HIHO S 2 , ENNIS S 1 , LEVVEY B 1 , SHINGLES H 1 , PARASKEVA M 1 , LEVIN K 1 , WESTALL G 1 , SULLIVAN L 2 , SNELL G 1

1 Lung Transplant Service, Alfred Hospital, Melbourne, 2 Australian Red Cross Blood Service, Australia

Introduction Antibodies to angiotensin type 1 receptor (AT1Rabs) have been linked to poorer graft outcome in both kidney (KTx) and lung transplant (LTx) recipients. In KTx, a decline in kidney function in the presence of AT1Rabs might solely reflect graft rejection, whereas this association in LTx would imply an alternate immunogenic process leading to an acute kidney injury (AKI).

Methods: In this single-centre observational study we explored the association between pre-LTx AT1Rabs and post-LTx AKI in 85 adult patients undergoing LTx July 2014- December 2023. AT1Rabs >17 U/ml were considered positive. Kidney function was assessed using the CKD-EPI formula from LTx until discharge. AKI was defined as a sharp increase (within 48 hours) in serum creatinine of ≥26.5 mmol/L.

Results: The mean age of the patients at LTx was 58 ± 10yrs and 60% were male. The mean concentration of serum AT1Rabs was 13±8 and 15/85 (18%) of the subjects had a positive titer. AKI occurred in 40/85 (47%) of cases post-LTx and was more prevalent in the AT1Rabs positive cohort (40% vs 73%, p=0.023). Accordingly, the decrease in kidney function was more pronounced in the AT1Rabs population (-26 ± 23 vs -41 ± 26 mL/min/1.73m 2 , p=0.022) (Figure 1). Positive AT1Rabs were associated with a four-fold higher risk of developing AKI (OR 3.88, CI 1.1-13.4, p=0.032).

Conclusions: Pre-LTx AT1Rabs are associated with AKI following LTx and might also be relevant as a mechanism of injury following KTx.

Figure 1. eGFR decrease post-LTx

DYNAMIC OF ANGIOTENSIN TYPE I RECEPTOR ANTIBODIES IS ASSOCIATED WITH POOR GRAFT FUNCTION FOLLOWING LUNG TRANSPLANT

DARIE A 1 , LEVVEY B 1 , SHINGLES H 1 , PARASKEVA M 1 , LEVIN K 1 , ENNIS S 1 , HIHO S 2 , SULLIVAN L 2 , WESTALL G 1 , SNELL G 1

1 Lung Transplant Service, Alfred Hospital, Melbourne, 2 Australian Red Cross Blood Service, Australia

Introduction Lung transplantation (LTx) saves the lives of patients with end-stage lung disease, but the longevity of transplanted lungs is much lower than that of other transplanted organs. Antibodies to angiotensin type 1 receptor (AT1Rabs) have been linked to poorer graft outcome.

Methods: In this single-centre, longitudinal, observational study we assessed 49 patients that underwent LTx July 2014 and October 2015 at The Alfred. AT1Rabs levels were measured pre-LTx and one-year post-LTx. AT1Rabs levels ≤10 U/ml were considered negative, >10 U/ml and ≤17U/ml intermediate, and >17 U/ml positive.

Results: The mean age at LTx was 59±9 and 53% were male. The mean follow up time was 7±3 years. There was a significant decrease in AT1Rabs levels after LTx and implementation of immunosuppressive therapy (12.3 U/l vs 9.8 U/l, p<0.001). The change in AT1Rabs levels between negative, intermediate and positive can be defined as increasing, stable or decreasing (Figure1):6% of patients had an increase in AT1Rabs levels, whereas 61% were stable and 33% had a decrease. A risk category increase was associated with a lower FEV1% predicted value at 12 months compared to patients with stable or decreasing risk category (60%vs92%vs82%, p=0.039). Additionally, a risk category increase was associated with baseline lung allograft dysfunction (p=0.025).

Conclusions: An increase in risk according to AT1Rabs levels is associated with poor graft function following LTX.

Figure 1. Dynamic of AT1Rabs after LTx. FU, Follow up

THE IMPACT OF DONOR AND RECIPIENT DIABETES ON PATIENT AND GRAFT SURVIVAL IN RENAL TRANSPLANT RECIPIENTS

ORSILLO A 1 , KHOLMURODOVA F 2 , CLAYTON P 1,2 , CHADBAN S 3 , WEIGHTMAN A 1 , IRISH GL 1,2

1 Central and Northern Adelaide Renal and Transplantation Service, The University of Adelaide, Royal Adelaide Hospital, 2 ANZDATA, South Australia, 3 Royal Prince Alfred Hospital, Sydney

Aims: The use of deceased kidney donors with diabetes is increasing in the context of the growing demand for organs for transplantation. We aimed to assess graft and patient survival when the donor, recipient or both have diabetes.

Methods: Data from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) were used to analyse first-time recipients of deceased-donor kidneys between 2004-2022. A Cox proportional hazards model compared the primary outcomes of death censored graft survival (DCGS) and overall patient survival across four combinations of donor/recipient diabetic status.

Results: There were 11,343 recipients amongst the four groups; n=7381 donor/recipient both non-diabetic, n=3249 recipient only diabetes, n=524 donor only diabetes and n=189 donor/recipient both diabetic. The mean age at transplant was 51 years (SD 12.6); 79.4% were deceased by brain death donors. Unadjusted DCGS was worse if both donor and recipient were diabetic (figure 1); this difference was maintained after adjustment (HR 1.707; CI 1.157-2.520; p =0.007). There was no difference in DCGS if donor only diabetes (HR 0.950; CI 0.757-1.192; p=0.658). Patient survival was poorest if both had diabetes (HR 1.779; CI 1.334-2.371; p = 0.000), followed by diabetic recipients with a non-diabetic donor (HR 1.383; CI 1.188-1.609; p=0.000).

Conclusions: These data support the use of diabetic donor kidneys for non-diabetic recipients, with no difference identified in graft survival. Diabetic donor/recipient combinations may lead to shorter graft and patient survival, therefore allocation in these circumstances must be approached with caution.

SKIN CANCER MORTALITY IN KIDNEY TRANSPLANT RECIPIENTS: AN AUSTRALIAN COHORT STUDY USING LINKED HEALTH DATA, 1980-2019

FORCEY D 1 , ROSALES B 1 , DE LA MATA N 1 , KELLY P 1 , WYLD M 1,2 , WYBURN K 3 , WEBSTER A 1,2,4

1 School of Public Health, University of Sydney, 2 Renal Medicine and Transplantation, University of Sydney, Westmead Hospital, 3 Nephrology and Renal Transplant, Royal Prince Alfred Hospital, Sydney, University of Sydney Medical School, 4 NHMRC Clinical Trials Centre, Westmead Hospital, Sydney

Aims: We sought to describe skin cancer mortality in Australian kidney transplant recipients and any differences by age, sex, initial state of registration on kidney replacement therapy and era.

Methods: This population-based cohort study of Australian kidney transplant recipients analysed data from the Australian and New Zealand Dialysis and Transplantation Registry from 01/01/1980 to 31/12/2019. Date and underlying cause of death were ascertained by data linkage with the National Death Index at the Australian Institute of Health and Welfare and classified using ICD10AM codes.

Results: Of the 20,954 transplant recipients with a total follow-up of 241,047 person-years (py), there were 280 deaths from skin cancer, 85 from melanoma and 195 from keratinocyte cancer. Skin cancer mortality rate was 116 per 100,000py (95% CI 103- 131) and rates fell each decade from 1980 to 2019. Caucasians account for 97% (n=271) of skin cancer deaths. Median time from first kidney transplant to death was 8 years (IQR 4-12 years) for melanoma and 12 years (IQR 7-18 years) for keratinocyte cancer. The mortality rate from skin cancer was highest in males (143 per 100,000py, 95% CI 124 – 163, compared to 76 per 100,000py, 95% CI 61 – 96 among females), those aged 50-59 years (463 per 100,000py, 95% CI 366 – 586), and among those in Queensland, followed by Western Australia and Tasmania (Figure 1).

Conclusions : Australian kidney transplant recipients have high rates of skin cancer mortality. Sex, age and state-based differences in skin cancer mortality may have implications for post-transplant screening programs and policy.

n deaths (%, of total number of deaths from skin cancer during study period, n=280), # Mortality rate per 100,000 population (95% CI) of Australian kidney transplant recipients (n=20,954), *Data combined for New South Wales and the Australian Capital Territory

INTEGRATING ARTIFICIAL INTELLIGENCE IN ORGAN TRANSPLANTATION DIAGNOSTICS: A COMPREHENSIVE EVALUATION USING THE PROMAD ATLAS

ROBERTSON H , LI J, PATRICK E, O’CONNELL P, ROGERS N

Centre for Transplant and Renal Research, The Westmead Institude for Medical Research, Sydney

Introduction: Advances in sequencing technologies have revolutionized our understanding of molecular markers in disease, particularly in organ transplantation. The PROMAD atlas, encompassing over 14,000 biopsy and 2,000 blood samples from various transplants, sets the stage for exploring artificial intelligence (AI)‘s role in diagnosing allograft dysfunction. This study evaluates AI’s diagnostic potential using PROMAD’s extensive dataset.

Methods: We developed two transcriptomic biomarkers from PROMAD’s 233 omics datasets for detecting allograft dysfunction in both biopsy and blood samples. These biomarkers were validated in a prospective cohort study at Westmead Hospital. Additionally, we utilized transformer architecture AI models to predict allograft dysfunction from histology slides, aiming to refine diagnostic processes.

Results: Our results demonstrate that a machine-learning model integrating information from multiple organs outperforms models trained solely on individual organs. Specifically, the pan-organ model achieved a mean area under the curve of 0.84 in predicting rejection across 2,000 peripheral blood samples. Our biopsy-based biomarker outperformed BHOT in predicting DGF, rejection and fibrosis in a prospectively recruited cohort. Similarly, our histology-based AI model showed promising comparability to more expensive omics-based biomarkers in diagnostic performance across DGF, rejection and fibrosis in our prospective cohort.

Conclusion: This study highlights AI’s transformative potential in organ transplantation diagnostics, offering a novel, highly accurate approach to predicting allograft dysfunction. By making our diagnostic tools publicly available, we provide a valuable resource for integrating AI into clinical practice, paving the way for improved patient outcomes.

Figure 1: ROC curves comparing BHOT (orange) and the data-derived panel from PROMAD (red) in predicting A. delayed graft function (DGF), B . biopsy-proven acute rejection, C . biopsy-proven fibrosis using the Australian Chronic Allograft Dysfunction (AUSCAD) as an external validation cohort.

IS LONG-TERM (>7 DAYS) EX-SITU NORMOTHERMIC MACHINE PERFUSION CAPABLE OF INDUCING REGENERATION IN HUMAN LIVERS?

NIU A , HUANG J, CHEN J, LAU N, LY M, RISBEY C, BABEKUHL D, YOUSIF P, HANSON K, DENNIS C, LIU K, MCKENZIE C, KENCH J, CRAWFORD M, MCCAUGHAN G, PULITANO C

Transplant Surgery, Royal Prince Alfred Hospital, Sydney

Background: Ex-situ normothermic perfusion offers a unique platform for regenerative therapy, opening the potential to cultivate livers from partial grafts for transplantation. Knowledge from hepatectomies suggest regenerative changes take place over at least 7 days, with an initial shift from glucose to lipid as the primary substrate for energy production. This study aims to assess liver regeneration during long-term normothermic machine perfusion (LT-NMP) using a multiomics approach.

Methods: Partial human liver grafts were perfused using our LT-NMP protocol. Nine grafts surviving >7 days were included. Liver viability was determined through haemodynamic parameters, bile production, glucose metabolism and lactate clearance. Liver regeneration was assessed via volumetric analysis of hepatocyte size and immunochemistry. Key signaling pathways associated with regeneration were identified through lipidomics, metabolomics, and next generation sequencing. Microvesicular and macrovesicular steatosis were assessed histologically.

Results: Throughout perfusion, 5 grafts displayed an increase in hepatocyte size. Progressive accumulation of microvesicular steatosis was observed after 7 days, reflective of a transient regeneration-associated steatosis (TRAS). Metabolomic and lipidomic analyses demonstrated an accumulation of intracellular triglycerides and membrane phospholipids and a reduction in free carnitine, suggesting a shift towards lipid utilisation for membrane synthesis, over mitochondrial β-oxidation. RNA sequencing identified novel gene expression.

Conclusion: Our results suggest that TRAS occurs during LT-NMP (>7 days). We observed lipid accumulation and changes in lipid metabolism, suggesting a coordinated response within regenerating hepatocytes to reserve lipids for membrane synthesis and cellular proliferation. These findings unveil the potential for hepatocellular regeneration during LT-NMP, fostering the future of liver transplantation.

INULIN SUPPLEMENTATION IMPROVES GLYCAEMIC CONTROL IN ACUTE KIDNEY TRANSPLANT RECIPIENTS – RESULTS FROM THE DIGEST TRIAL

SINGER J 1 , GILBERT A 1 , YING T 1 , MACIA L 2 , WU H 1 , CHADBAN SJ 1

1 Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, 2 Faculty of Medicine and Health, University of Sydney, Sydney

Aims : Dysglycaemia following kidney transplantation is common, with both new onset diabetes after transplant (NODAT) and impaired glucose tolerance (IGT) conferring increased risks of cardiovascular disease and death. The gut microbiome is associated with the development of metabolic disease, and prebiotic enhancement of the microbiota has been shown to improve glycaemic parameters, although this has not been studied in KTRs.

Methods : We conducted a single centre, open-label, randomised trial, where 40 acute KTRs were randomised at 28 days post-transplant to a 4-week period of inulin supplementation (20 g/day) or standard care. Glycameic metrics were captured using continuous ambulatory glucose monitoring (CGM) and changes in gut microbiota through 16s rRNA sequencing.

Results : Participants were male (27/40, 68%), age 49 ± 14 years (mean/SD), with diabetes present in 9 (22%) pre-transplant, and 16 (40%) post-transplant. Inulin was feasible, tolerable, and safe in the early post-transplant period. In non-diabetic KTRs, inulin improved glycaemic measures at week 8 with a reduction in mean glucose (5.7 vs 6.4; mmol/L, p = 0.019), time above target range (>7.8 mmol/L, 9.7 vs 23.0; %, p = 0.04), and reduced glucose variability (mean amplitude of glycaemic excursions (MAGE), 2.2 vs 3.4; mmol/L, p = 0.04).

Conclusions : Inulin supplementation is a feasible intervention that improves dysglycaemia in the early post-transplant period. Larger clinical trials are now indicated to assess its role in preventing NODAT.

Figure 1 : Ambulatory glucose profiles of non-diabetic KTRs during the fourth week of inulin supplementation of standard care.

DRUG REPURPOSING IN THE CONTEXT OF ACUTE KIDNEY INJURIES

MOUDGIL A 1 , DESHPANDE A 1 , ROBERTSON H 1 , LI J 1 , PATRICK E 2 , ROGERS N 1

1 Centre for Transplant and Renal Research, The Westmead Institude for Medical Research, 2 School of Mathematics and Statistics, University of Sydney

Introduction : Acute kidney injury (AKI) continues to be a major clinical concern, involving a fifth of all adult hospital admissions. A lack of treatment other than standard-of-care, there is a substantial unmet clinical need to determine alternative therapy.

Methods: We identified publicly available RNA sequencing datasets of ischemia reperfusion injury (IRI) in mice and developed a customised bioinformatics pipeline to determine differentially expressed genes (DEG) and conserved pathways. These were mapped onto drug databases to find potential therapeutic agents. Male, C57BL/6 mice underwent bilateral renal IRI (20 minutes/36°c) and were treated peri-operatively with relevant drugs. Analysis of renal function, histology and biomolecular phenotyping was performed 24-hours post-operatively.

Results: We curated a list of 24 DEG in IRI and mapped these against KEGG and Gene Ontology databases, revealing changes in metabolic processes as the most crucial gene disturbances. We mapped this data to 22 drug databases, identifying perhexiline, disulfiram and MCC950 as potential drug repurposing candidates. Administration of either drug prior to IRI was protective against injury, demonstrating lower serum creatinine, histological injury and cell death (TUNEL staining). Disulfiram, but not perhexiline, limited pro-inflammatory cytokine transcripts in kidney tissue. Perhexiline decreased fatty acid accumulation (Oil Red O staining) and upregulated expression of anti-apoptotic factors, including Bcl-xL. MCC950 had no impact on the severity of IRI.

Conclusion: Bioinformatics analyses enabled us to characterise novel transcriptomic features of AKI and identify several drugs - perhexiline and disulfiram - that can be effectively repurposed for testing in AKI models and subsequent clinical application.

THE IMPACT OF FEMALE SEX AND INTERSECTIONAL DISADVANTAGE ON ACCESS TO DECEASED KIDNEY TRANSPLANTATION IN AUSTRALIA

VITAGLIANO T 1 , DE LA MATA N 1 , HSU P 2 , ALEXANDER S 3 , WYBURN K 4 , WYLD M 5

1 Faculty of Medicine and Health, University of Sydney, 2 Department of Allergy and Immunology, The Children’s Hospital at Westmead, Sydney, 3 Centre for Kidney Research and Department of Nephrology, The Children’s Hospital at Westmead, Sydney, 4 Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, 5 Department of Renal and Transplant Medicine, Westmead Hospital, Sydney

Aims: We sought to determine if there are sex-based disparities in access to the deceased donor waitlist and/or transplantation, and how intersectional disadvantages such as minority ethnicity, low socio-economic position, cause of kidney failure, and high co-morbidity burden may interact with such disparities, in contemporary Australia.

Methods: A cohort study using the ANZDATA registry (2006-2021) to explore the associations between sex and intersectional disadvantage and outcomes including waitlisting, deceased donor transplantation, and death. Cox proportional hazards models, two-way interaction models and competing risk analysis adjusted for baseline characteristics were used.

Results: 41,227 patients commenced dialysis during the study period, of which 15,454 (38%) were female, and were followed for 122,400 person-years. In our fully adjusted model, females were 19% less likely to be waitlisted (Hazard Ratio[HR]-0.81;95%CI:0.77-0.84), than their male peers. The sex-based disparity in transplant waitlisting was larger for females with intersectional disadvantage including older age (females >45yrs HR-0.78;95%CI:0.74-0.83 compared to their male peers), ethnic minorities (eg. female Aboriginal and Torres Strait Islander HR-0.57;95%CI:0.48-0.68, female Asian HR-0.76;95%CI:0.69-0.84), low socio-economic position (HR-0.76; 95%CI: 0.69-0.83), diabetic kidney disease as the cause of kidney failure (HR-0.63;95%CI:0.57-0.69), and having ≥3 co-morbidities (HR-0.69;95%CI:0.57-0.84). There was no significant difference in deceased transplantation rates once waitlisted, or death on the waitlist for any groups.

Conclusions: Females have significantly less access to kidney transplant waitlisting than their male peers, and this sex-based disparity is amplified for females with intersectional disadvantage. Once waitlisted, there are no sex-based disparities in rates of deceased donor transplantation or death.

A STANDARDISED METHOD OF MULTI-VISCERAL ORGAN RETRIEVAL FOR TESTING EX VIVO MACHINE PERFUSION IN A LARGE ANIMAL MODEL

BASTIAN J , BHATTACHARJYA R, DANIEL D, KANHERE A, BARNETT D, BHATTACHARJYA S

1 Transplant Surgery, University of Adelaide, South Australia

Aim: To develop a replicable method for assessing the quality of ex vivo machine perfusion (EVMP) of multi-visceral abdominal blocks by various novel function tests.

Methods: Twelve Yorkshire pigs were procured before random allocation to one of three preservation groups: static cold storage, normothermic machine perfusion with blood and isothermic machine perfusion with an acellular perfusate (n = 4 for all groups). Following induction of anaesthesia, midline laparotomy gained access to the animals’ abdomen. Multi-visceral blocks composed of the liver, both kidneys, pancreas and proximal 100 cm of small bowel were surgically retrieved, with complete thoraco-abdominal mobilisation of the aorta and vena cava. Four units of autologous blood was collected from the supra-hepatic vena cava, prior to cross clamping of the aorta.

Results: Successful short term preservation was achieved for five hours, with en bloc organ function outcomes comparable in respective techniques. For the MP groups there were no statistical differences seen in any of the composite measures including acid base, arterial-venous oxygen differential and tissue ATP analyses. The insulin stimulating effect of GLP-1 demonstrated active small bowel and pancreatic function following luminal stimulation. Fluorescein angiography provided qualitative information of the vascular integrity of the blocks.

Conclusion: Multi-visceral transplantation saves lives. However, there are currently limited models for investigating the quality of preservation in multi-visceral abdominal blocks. This study provides proof of concept that multi-visceral blocks can be feasibly preserved for five hours by ex vivo machine perfusion under different conditions.

Fig 1: Abdominal block in situ following aortic cross clamp

INTRAGRAFT mRNA CHANGES WITH INTRAVENOUS IMMUNOGLOBULIN VERSUS STANDARD CARE IN CHRONIC ANTIBODY MEDIATED REJECTION-VIPAR RCT

THARMARAJ D 1 , TESCH G 1 , OLSHANSKY M 2 , POLKINGHORNE K 3 , DAYAN S 4 , KWAN E 4 , MARK T 5 , LEE D 6,7 , MOUNT P 7 , WONG G 8 , WYBURN K 9 , LIM W 10 , KERR P 5 , KANELLIS J 5 , NIKOLIC-PATERSON D 5 , MULLEY W 1

1 Departments of Nephrology and Medicine, Monash Medical Centre and Monash University, Clayton, Australia, 2 Monash Genomics and Bioinformatics, Monash University, Clayton, Australia, 3 Departments of Nephrology and Medicine and Department of Epidemiology and Preventative Medicine, Monash Medical Centre and Monash University, Clayton, Australia, 4 Department of Anatomical Pathology, Monash Medical Centre, Clayton, Australia, 5 Department of Nephrology, Monash Medical Centre, Clayton, Australia, 6 Departments of Renal Medicine and Eastern Health Clinical School, Eastern Health, Box Hill, 7 Department of Nephrology, Austin Health, Heidelberg, 8 Department of Renal Medicine and National Pancreas Transplant Unit, Westmead Hospital, Sydney, 9 Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, 10 Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, 11 Department of Nephrology, Monash Medical Centre, Clayton

Background: Intragraft gene transcripts have prognostic significance in antibody-mediated rejection (AMR). Mechanism of action of intravenous immunoglobulin (IVIg) and its impact on gene expression in chronic AMR (cAMR) is unknown.

Aims: To assess intragraft gene transcript changes associated with IVIg therapy.

Methods: The VIPAR study compared clinical and histological outcomes in 30 kidney transplant recipients with cAMR randomised 1:1 to 6 months of IVIg versus no-IVIg. mRNA extracted from allograft biopsies taken at 0,3,6 and 12-months post-diagnosis was analysed using NanoString (B-HOT panel). Gene transcript differential expression (DE) was assessed using paired and time-course analyses. DE was defined as >1.5x gene fold change between groups with an adjusted p-value<0.05.

Results: The VIPAR study demonstrated reduced deterioration in allograft injury and eGFR with IVIg relative to no-IVIg. Paired analysis (combined 3,6,12months) revealed 59 downregulated genes in allografts from IVIg-treated relative to no-IVIg-treated patients. Nine of the top 12 DE genes were B-cell related (Table). These genes most commonly associated with haematopoietic, adaptive immune system and T-cell receptor signalling pathways. 12-month time-course analysis demonstrated different profiles for the IVIg relative to no-IVIg group for 21 genes, with one increasing (LTBR) and 20 decreasing including B-cell (PAX5, CD22, SPIB, FCRL2, MS4A1, AICDA, TCL1A, IL4), T-cell/NK cell (CCR4, TNFSF14, CD244,IL4), pro-inflammatory (LTA, CXCL2) and pro-fibrotic (JUN) transcripts. Whilst 13 potentially injurious genes were upregulated in the timecourse analysis of the no-IVIg group, 22 genes were significantly downregulated in the IVIg group.

Conclusion: IVIg impacts intragraft B-cell, T-cell, pro-inflammatory and pro-fibrotic gene expression, providing a mechanistic insight into its therapeutic benefits in cAMR.

Table. Top-12 downregulated DE genes in IVIg vs. no-IVIg paired analysis

CHARACTERISING PANCREATIC ORGANOIDS FROM HEREDITARY PANCREATITIS PATIENTS

ZUIANI J 1 , WU D 1 , DROGEMULLER C 2 , PERKINS G 1 , COATES T 2

1 School of Medicine, Faculty of Health Sciences, University of Adelaide, 2 Central Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, South Australia

Introduction: Hereditary pancreatitis (HP) is an inflammatory genetic condition typically caused by uncontrolled activation of trypsin within the pancreas. Animal models struggle to recapitulate this disease due to discrepancies in key HP genes such as PRSS1 and SPINK1 . Pancreatic organoids provide the opportunity to better study this condition, allowing for modelling of patient specific mutations. We have grown organoids both from healthy pancreas and from PRSS1 mutant HP samples.

Methods: Pancreatic organoids were derived from samples taken from islet isolations, with HP samples originating from patients undergoing total pancreatectomy with islet auto transplantation (TPIAT). These organoids were embedded within a Matrigel matrix and cultured with a complex organoid growth medium. Phase contrast microscopy images were taken to track organoid growth over time. Organoids were further characterized via qPCR and immunohistochemistry to determine whether they maintained an acinar phenotype and gene expression relevant to HP.

Results: Organoids were successfully grown from HP samples and displayed growth comparable to those of normal pancreas. Characterization of these organoids showed expression of acinar genes including PRSS1 and amylase, alongside the presence of ductal genes such as KRT19 , indicating the beginnings of acinar to ductal metaplasia (ADM)

Conclusions: We have demonstrated one of the first instances of growing organoids from HP patient samples, displaying that they maintain the expression of relevant acinar genes. These organoid models have the potential to provide a platform for deeper research into HP, including a better understanding of unique patient gene mutations and the development of new treatments.

THE EPIDEMIOLOGY OF HEREDITARY PANCREATITIS IN AUSTRALIA AND ITS EFFECT ON PATIENT OF TOTAL PANCREATECTOMY WITH ISLET AUTO-TRANSPLANTATION (TPIAT)

WU D 1 , ZUIANI J 1 , DE SOUSA S 2 , ADELSON D 3 , COATES T 4

1 School of Medicine, University of Adelaide, 2 Department of Endocrine and Metabolism, Royal Adelaide Hospital, 3 School of Molecular and Biomedical Science, University of Adelaide, 4 Renal and Transplantation Unit, Royal Adelaide Hospital, South Australia

Introduction: Hereditary pancreatitis (HP) is an inflammatory genetic condition typically caused by uncontrolled activation of trypsin within the pancreas. Animal models struggle to recapitulate this disease due to discrepancies in key HP genes such as PRSS1 and SPINK1 . Pancreatic organoids provide the opportunity to better study this condition, allowing for modelling of patient specific mutations. We have grown organoids both from healthy pancreas and from PRSS1 mutant HP samples.

Methods: Pancreatic organoids were derived from samples taken from islet isolations, with HP samples originating from patients undergoing total pancreatectomy with islet auto transplantation (TPIAT). These organoids were embedded within a Matrigel matrix and cultured with a complex organoid growth medium. Phase contrast microscopy images were taken to track organoid growth over time. Organoids were further characterized via qPCR and immunohistochemistry to determine whether they maintained an acinar phenotype and gene expression relevant to HP.

Results: Organoids were successfully grown from HP samples and displayed growth comparable to those of normal pancreas. Characterization of these organoids showed expression of acinar genes including PRSS1 and amylase, alongside the presence of ductal genes such as KRT19 , indicating the beginnings of acinar to ductal metaplasia (ADM)

Conclusions: We have demonstrated one of the first instances of growing organoids from HP patient samples, displaying that they maintain the expression of relevant acinar genes. These organoid models have the potential to provide a platform for deeper research into HP, including a better understanding of unique patient gene mutations and the development of new treatments.

TRENDS IN HOSPITAL UTILISATION AMONG CHILDREN BORN TO TRANSPLANTED MOTHERS IN THEIR FIRST DECADE OF CHILDHOOD

HEWAWASAM E 1 , DAVIES C 1 , LI Z 2 , SULLIVAN E 2 , MCDONALD S 1 , JESUDASON S 3

1 ANZDATA, South Australian Health and Medical Research Institute (SAHMRI), 2 College of Health Medicine and Wellbeing, University of Newcastle, NSW, 3 Central Northern Adelaide Renal and Transplantation Services (CNARTS), Royal Adelaide Hospital South Australia

Aims: We investigated hospital utilisation in the initial decade for children of transplanted mothers (C-Tx) versus those of mothers who had not received kidney replacement therapy (C-non-KRT).

Methods: We utilised linked Australia and New Zealand Dialysis and Transplant Registry, perinatal (births ≥20 weeks gestation, 1991-2013) and hospital admission datasets (until 2018) in SA, WA, ACT and NSW.

Results: Of 1,865,425 babies with 6,063,327 hospital admissions, the C-Tx had 37 birth and 551 subsequent admissions (n=99 babies), with a median follow-up duration of 2.5 years [IQR: 0.9-5.3] (vs 2.9 years [1.1-5.4] C-non-KRT, p=0.03). C-Tx had longer birth admissions (median 6 days, IQR: 4-16) than the C-non-KRT (3 days, 2-5, p<0.001). Almost 70% of C-Tx (vs 34% C-non-KRT) had perinatal-related admissions, associated with gestational issues, respiratory/cardiovascular diseases, haemorrhagic/haematological conditions, endocrine/metabolic disorders, infections and pregnancy complications, ~3-5 times higher than C-non-KRT (p<0.05) (Table 1). Subsequent admissions for respiratory, nervous system, and endocrine/metabolic diseases were more common in C-Tx (7-29%) than the C-non-KRT (4-24%), p<0.05. Prematurity (57% C-Tx vs 8% C-non-KRT) and pre-eclampsia (30% Tx vs 6% non-KRT), as key determinants of neonatal health, were explored. Preterm C-Tx had increased respiratory-related subsequent admissions (41%) than other preterm children (26%, p<0.001). Among women with pregnancy-induced hypertension (including pre-eclampsia), C-Tx had more perinatal conditions (80% vs 51%), endocrine/metabolic diseases (8% vs 4%), and respiratory diseases (35% vs 23%), p<0.05.

Conclusions: This first Australian study of post-birth outcomes in C-Tx revealed extended hospital stays and increased perinatal/respiratory illnesses. These children may require ongoing follow-up in childhood

Table 1. Major disease domains in birth and subsequent hospital admissions for children of transplanted and Non-KRT mothers

a Diagnostic codes missing for 65 babies in non-KRT

b Diagnostic codes missing for 5 babies (106 admissions) in transplant and 37,095 babies (824,944) admissions non-KRT

- P-values only reported if event rate ≥10

KIDNEY TRANSPLANT WAITLIST OUTCOMES AFTER DECLINE OF FIRST DECEASED DONOR KIDNEY OFFER: A DATA LINKAGE STUDY 2006-2019

BALDWIN H , ROSALES B, HEDLEY J, DE LA MATA N, AU E, WYBURN K, WEBSTER A

School of Public Health, University of Sydney, New South Wales

Aims: Deceased donor kidney offers may be declined over concerns around quality, donor characteristics, and biovigilance. We aimed to describe patient outcomes after an offer is declined and investigate the impact of patient characteristics on the rate of decline and subsequent outcomes.

Methods: We used linked data from the NSW Biovigilance Register (SAFEBOD) for all people entering the kidney transplant waitlist in NSW, 2006−2019. Rates of decline of first offer and subsequent outcomes were examined. Time from decline to transplantation was estimated, by patient characteristics, using Kaplan-Meier curves.

Results: Of 2305 people waitlisted, 1760 (76.4%) received at least one offer, of which 1129 (64.1%) were declined. Rates of offer decline varied significantly by age (18-44 years, 70.0%; over 65, 58.5%, p =0.01), ethnicity (Asian, 79.3%; Australia and New Zealand, 79.3%, p <0.001), blood group (B, 84.2%; AB, 57.7%, p <0.001) and sensitisation (PRA<10, 61.3%; PRA≥85, 75.8%, p <0.001). Most patients (n=995, 88.1%) received at least one subsequent offer, and 755 (66.9%) subsequently received a deceased donor transplant (Figure 1). Median time from decline to transplantation was 6.0 months (IQR 2.0-14.9). There was no significant difference in KDPI between declined and subsequently accepted kidneys. Univariable analyses suggested differences in time from initial decline to transplantation by blood group, age, ethnicity and sensitisation.

Conclusions: Rates of declining deceased donor kidney offers varied significantly by age, ethnicity, blood group and sensitisation. There was no evidence of quality difference between declined and later accepted kidneys. Further investigation is needed to better understand the impact of declining a deceased donor kidney for different patient groups.

Figure 1. Cumulative frequency distribution of five year outcomes for people entering the kidney waitlist in NSW, 2006-2019, whose first deceased donor kidney offer was declined (n = 1129).

COMMON CANCER TRANSMISSION andamp; NON-TRANSMISSION IN DECEASED ORGAN DONORS andamp; TRANSPLANT RECIPIENTS: NSW DATA-LINKAGE STUDY 2010-2018

ROSALES BM 1 , JOHNSTON C 1 , HEDLEY J 1 , DE LA MATA N 2 , CAVAZZONI E 3 , VAJDIC CM 4 , WHITE S 1 , KELLY P 2 , WYBURN K 5 , WEBSTER AC 2

1 Centre for Organ Donation Evidence (CODE), University of Sydney, 2 School of Public Health, University of Sydney, 3 NSW Department of Health, NSW Organ and Tissue Donation Service, 4 The Kirby Institute, University of New South Wales, 5 Nephrology and Renal Transplant, Royal Prince Alfred Hospital, Sydney

Aims: We aimed to estimate the transmission risk of common cancers (colorectal, breast and prostate) in deceased organ donation and identify missed opportunities for donation in an Australian cohort.

Methods: We analysed Organ and Tissue Donation Service referral data from actual deceased organ donors, transplant recipients, and potential donors forgone in NSW from 2010 to 2018, linked to the Central Cancer Registry (CCR) from 1972 to 2018. We categorised colorectal, breast, and prostate cancers using ICD-O-3 classification and stratified transmission risk according to the TSANZ Clinical Guidelines.

Results: Of 5,624 people referred for consideration for organ donation, 933 (17%) proceeded to donate. Of these, six (<1%) had a history of any common cancer registered in the CCR, including one high-risk breast cancer (>10%) and five prostate cancers with varying risk levels. There was no evidence of “Probable/Proven” transmission in the nine recipients from the donors with common cancer (Table 1). We identified 169 potential donors forgone who were suspected of a history of common cancer. Of these, six (4%) had no cancer registered in the CCR, and 39 (23%) had registered cancers classified as minimal-to-low (0.1%-<2%) risk. Including these donors would have increased the donor pool by 4.8% from 2010 to 2018.

Conclusions: We did not find any transmissions from donors with identified common cancers, indicating that organs from these donors are suitable for transplantation. Continuous review of transmission and non-transmission events in organ donation could ensure risk assessments remain up-to-date.

Table 2. Probable/Proven transmission from deceased organ donors with breast or prostate cancer

SEROLOGICAL RESPONSES AND CLINICAL OUTCOMES TO 3-DOSE COVID-19 VACCINATION IN KIDNEY TRANSPLANT AND DIALYSIS RECIPIENTS

THARMARAJ D 1 , BOO I 2 , O’HARA J 3 , SUN S 4 , POLKINGHORNE K 5 , DENDLE C 6 , TURNER SJ 3 , VAN ZELM M 7 , DRUMMER H 2 , KHOURY G 8 , MULLEY W 1

1 Department of Nephrology and Medicine, Monash Medical Centre and Monash University, Clayton, 2 Burnet Institute, Melbourne, 3 Department of Microbiology, Biomedicine Discovery Institute Monash University, Clayton, 4 Department of Immunology and Pathology, Burnet Institute, Melbourne and Monash University, Clayton, 5 Departments of Nephrology, Medicine, Epidemiology and Preventative Medicine, Monash Medical Centre and Monash University, Clayton, 6 Departments of Infectious Diseases and Medicine, Monash Medical Centre and Monash University, Clayton, 7 Department of Immunology and Pathology, Monash University, Clayton Victoria, 8 Department of Microbiology, Burnet Institute, Melbourne and Biomedicine Discovery Institute Monash University, Clayton

Background: Kidney transplant recipients (KTRs) and people receiving dialysis have a higher risk of severe COVID-19 disease and may be less protected post-vaccination due to blunted vaccine responses.

Aim: To assess serological responses and predictors of sero-response to a 3-dose SARS-CoV-2 vaccination schedule in KTRs and people on dialysis, and to determine the relationship between responses and breakthrough infection.

Methods: Plasma from 30 renal transplant recipients and 17 people receiving dialysis was tested for anti-Spike receptor binding domain (RBD) IgG and neutralizing antibodies (NAb) to the ancestral strain and Omicron BA.2 variant after dose 2 and 3 of vaccination.

Results: After three doses, KTRs achieved lower anti-RBD IgG levels and NAb titres than people receiving dialysis (p<0.05; Figure). Seropositive cross-reactive Omicron neutralization levels were achieved in 11/27 (40.7%) KTRs and 11/14 (78.6%) dialysis recipients, respectively. ChADOx-1 containing vaccine schedules, higher mycophenolate dose (>1gm/day), and lower absolute B-cell counts predicted poor serological responses in KTRs. More KTRs subsequently contracted SARS-CoV-2 infection (14/30; 47%) than dialysis recipients (5/17; 29%) and had more severe disease. Those with SARS-CoV-2 breakthrough infections had lower inter-dose incremental change in anti-RBD IgG levels (4.45 µg/ml (0.5 – 41.5) versus 41.2 µg/ml (11.1-87.8)) and ancestral NAb titres (IC50: 2.5 (-5.7 – 136.7) versus 133.5 (14-524.1)), p<0.05.

Conclusion: Serological responses to SARs-CoV-2 vaccination in KTRs lag behind their dialysis counterparts. KTRs remained at high-risk of breakthrough infection after their primary vaccination schedule underlining their need for booster doses, strict infection control practices and close surveillance.

Figure. Transplant and dialysis a) Anti-RBD IgG levels b) Ancestral NAb c) Omicron (BA.2)) levels at dose 2 and 3. Positive cut-off thresholds for Anti-RBD IgG levels and reciprocal dilution IC50 NAb titres are >0.4µg/ml and >20 (reciprocal dilution IC50) respectively. ns ≥0.05, * =p <0.05, ** p <0.01, *** p <0.001, **** p <0.000

EXPOSURE TO ANAEROBIC ANTIBIOTICS AND RISK OF ALLOGRAFT REJECTION FOLLOWING LIVER TRANSPLANT

SMIBERT O 1 , SARAH V 2 , ANGELA L 3 , TESTRO A 3 , MARIE S 3 , AVIK M 3 , JASON T 1 , KATE M 4 , SLAVIN M 5 , KWONG J 1

1 Infectious Diseases, Austin Health, 2 Department of Medicine, St Vincent’s Hospital, Melbourne, 3 Liver Transplant Unit, Austin Health, 4 Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, USA, 5 Department of Infectious Diseases, Peter MacCallum Cancer Centre

Aims: The gut microbiota has been associated with allograft rejection following liver transplant (LTx). Antibiotics (Abx) alter the gut microbiota and may represent an independent risk factor for rejection. We sought to explore the association between Abx exposure during the 30 days preceding and 365 days following LTx at a single tertiary health center in Melbourne, Australia between January 2015 – June 2022.

Methods: We classified and grouped Abx as having an anaerobic spectrum of activity or not. Peri-LTx piperacillin-tazobactam and post-LTx prophylaxis with trimethoprim-sulfamethoxazole were excluded. Abx post-transplant were assessed as time-varying covariates. Rejection at 1 year was assessed using Cox proportional hazards models, unadjusted and adjusting for other confounders.

Results: During the study period, 462 patients underwent LTx with 20.8% (96/462) experiencing rejection at 1 year. In univariate analyses there was no association between any pre-LTx Abx and incidence of rejection. In contrast, exposure to any anti-anaerobe Abx following LTx was associated with a significant increase in the incidence of rejection (SHR 2.25; 95% CI 1.40 to 3.62; p=0.001). After adjustment for potential confounders identified in univariate analyses (CMV-status, cold-ischemia time, MELD, CCI and liver disease), exposure to any anaerobe-targeting Abx remained significantly associated with increased risk of rejection at 1 year in multivariable analyses (SHR 2.34; 95% CI 1.41 to 3.86; p=0.001).

Conclusions: Exposure to anaerobe-targeting Abx following transplant was an independent risk factor for rejection. This effect may be mediated by Abx-induced disruption of the gut microbiota and serves as a reminder of the value of antimicrobial stewardship programs in the peri-transplant setting.

ACTIVATION OF HUMAN CD4+CD25+CD127lo TREG WITH ALLOANTIGEN AND RIL-2 INDUCES IFNGR

AL-ATIYAH R 1,2 , VERMA ND 1,2 , KAWALIA P 1,2 , TRAN G 1,2 , HODGKINSON SJ 1,2,3,4 , HALL BM 1,3

1 Immune Tolerance Group, Ingham Institute for Applied Medical Research, NSW, 2 South West Sydney Clinical School, University of New South Wales, 3 Department of Neurology, Ingham Institute for Applied Medical Research 4 Liverpool Hospital, New South Wales

Aims: In rats, CD4 + CD25 + Treg activated with rIL-2/alloantigen (alloAg), express more Foxp3 and CD25 in addition to IFN-g (IFNGR) and IL-12 (IL-12Rb2) receptors, making them more potent suppressors of specific-alloactivation. Here we examined activation of human alloAg-specific CD4 + CD25 + CD127 lo Foxp3 + Treg.

Methods: CD4 + CD127 lo CD25 + Treg isolated by FACS from healthy volunteers’ blood were cultured for 4 days with rIL-2 and irradiated alloAg. Cells were examined using flow cytometry for shifts in Treg subpopulations; resting Pop I (Foxp3 + CD25 + CD45RA + ), activated Pop II (Foxp3 hi CD25 hi CD45RA - ), Treg and activated effector T cell Pop III (Foxp3 + CD25 + CD45RA - ) and chemokine receptors; CXCR3 (Th1), CCR6 (Th17), CCR4 (Th2). Cells were stained for foxp3 and ifngr using RNAscope.

Results: tTreg cultured alone had less Pop II than fresh tTreg (1.3% vs 8.6%). Culture with alloAg preserved Pop II (12% vs 8.6%). IL-2 increased Pop II (5/8 experiments), similar to alloAg/rIL-2 (6/8 experiments). Pop II in unfractionated Treg cultured with IL-2 or alloAg or alloAg/IL-2, showed similar CXCR3 expression. RNAscope showed Treg cultured alone or with IL-2 had less foxp3 + cells than fresh Treg but remained ifngr - . Treg with alloAg had single foxp3 + and ifngr + cells, while Treg with alloAg/rIL-2 also had foxp3 + ifngr + cells. Enriched Pop I cells cultured alone lost Foxp3 expression. Culture with alloAg/rIL-2 produced Foxp3 hi CD25 + CD45RA + cells that remain CXCR3 - CCR6 - . Pop II cells cultured alone died, but with rIL-2 or with alloAg, Foxp3, CD25 and CCR6 expression increased, while maintaining CCR4 and CXCR3 expression. Pop III had some cells expressing less Foxp3 while others increased Foxp3 and CD25 expression, shifting to Pop II.

Conclusion: Human tTreg stimulated with alloAg and rIL-2 induced IFNGR.

BK NEPROPATHY IN KIDNEY TRANSPLANTATION WHERE ALEMTUZUMAB IS USED AS AN INDUCTION AGENT -PREVALANCE MANAGEMENT GRAFTOUTCOME

RAMASWAMI AP , MOHAMEDALI Z, KOUSIOS A, CHARIF R

Department of Renal Medicine, Hammersmith Hospital, UK

AIMS Following kidney transplantation, BK virus-associated nephropathy (BKVAN) occurs in 1 to 10% of kidney transplant recipients (KTR) and represents a major cause of graft loss 1 . There is limited data on BKVAN epidemiology after Alemtuzumab induction 2 . We conducted a retrospective study including all kidney transplant recipients with a biopsy-proven diagnosis of BKVAN between 2007 and 2022 in Hammersmith hospital, to determine the incidence and outcomes of BKVAN.

RESULTS Eighty-nine cases of BKVAN were identified among 2,831 kidney transplantations (3.1% prevalence). At the end of follow up, 40.5% of our patients with a diagnosis of BKVAN were noted to have graft failure. Survival without return to dialysis with stable graft function was seen in 59.5% of patients during follow-up. Steroid had a definite role in the treatment of BKVAN and was beneficial with graft survival (5/16, 32% p=0.03) especially in those patients whose histology showed interstitial inflammation changes of greater than 20 %. Patients with BKVAN on MMF at diagnosis had better allograft survival (42.3% vs 26.9% p=0.03), than patients on CNI alone. The raised viral load > 4 log 10/ml is associated with extensive histological lesions with interstitial inflammation changes more than 20% (p=0.01) and persistence of BK virus infection (p=0.03). The risk factors for graft loss were augmentation of immunosuppression for rejection episodes (n=18/28,64% p=0.01), persistent BK Viremia (63.3% vs 36.7% p=0.01), rejection post-BK nephropathy (64% vs 35% p=0.03), moderate to severe IFTA in repeat biopsy (74%vs 26%) and mean increase in creatinine from baseline (42.51 vs 27.33 umol/L, p=0.001).

CONCLUSION: Our study demonstrates that augmented immunosuppression for rejection, higher viral loads, reduced renal function, increased IFTA, non-resolution of viraemia and rejection are the main factors of graft loss in patients with BKVAN. In addition, the use of steroids and IVIG in addition to immunosuppression reduction may have a protective role, particularly in those patients with prominent interstitial inflammation.

References :

1.Kant S, Dasgupta A, Bagnasco S, Brennan DC. BK Virus Nephropathy in Kidney Transplantation: A State-of-the-Art Review. Viruses. 2022 Jul 25;14(8):1616.

2.Korneffel K, Gehring B, Rospert D, Rees M, Ortiz J. BK Virus in Renal Transplant Patients Using Alemtuzumab for Induction Immunosuppression. Exp Clin Transplant. 2020 Oct;18(5):557-563. doi: 10.6002/ect.2019.0041. Epub 2019 Jul 19.

Table: Outcome of BK nephropathy

KIDNEY TRANSPLANTATION OF HEPATITIS C VIRAEMIC DONORS TO HEPATITIS C NEGATIVE RECIPIENTS: A SINGLE-CENTRE AUSTRALIAN EXPERIENCE

SUN J 1 , LAM D 1 , THOMPSON A 2 , IERINO F 3 , GOODMAN D 3 , LIU K 4 , WYBURN K 1

1 Renal and Transplantation Unit, Royal Prince Alfred Hospital, Sydney, 2 Transplant Department, St Vincent’s Hospital, Melbourne, 3 Renal and Transplantation Unit, St Vincent’s Hospital, Melbourne, 4 Transplant Department, Royal Prince Alfred Hospital, Sydney

Aim: The introduction of direct acting antivirals (DAA) targeting HCV has permitted transplantation of hepatitis C NAT positive (HCV+) kidneys into HCV negative (HCV-) recipients, and is a strategy that may help expand the deceased donor organ pool and shorten waitlist times. We present a single-centre case series of eight HCV- recipients who received kidney transplants from HCV viraemic deceased donors.

Methods: Most recipients were enrolled in the REPLACE study, an open-label pilot clinical trial aimed to examine the safety and feasibility of such donations in Australia. HCV- recipients receiving HCV+ kidneys were treated with 12 weeks of the DAA glecaprevir/pibrentasvir after confirmed transmission of HCV infection under a hepatologist’s supervision. Patients were followed up at 4, 12, and 24 weeks post-treatment, with the primary endpoint being sustained virological response (SVR), defined as undetectable serum HCV RNA levels 12 weeks post-treatment. There were no significant drug-drug interactions during follow-up.

Results: Seven out of eight (88%) patients completed the follow-up, with one death occurring at 13 weeks post-transplant, secondary to an ischaemic cardiac event. All patients achieved SVR following DAA therapy with excellent graft function at 12 and 24 weeks post-treatment, with median serum creatinine of 140umol/L (IQR 83-155) and 151umol/L (IQR 90-151) respectively. Recipient outcomes are summarised in Table 1.

Conclusions: Our results demonstrate the early safety and efficacy of utilising HCV+ kidney transplants in HCV- recipients. Long-term follow-up is ongoing. It is important to educate clinicians and patients on the benefits of this strategy to help increase donation rates and improve patient outcomes.

Table 1. Characteristics and outcomes of HCV- recipients of HCV+ kidneys.

DELIVERY OF REGULATORY T-CELL THERAPY VIA EX-SITU MACHINE PERFUSION OF THE LIVER

HANN A , DAVIES SP, FIANCETTE R, CLARKE G, MAO J, RICHARDSON N, WOOTTON G, BOZWARD A, KAYANI K, RONCA V, AFFORD S, PERERA T, OO Y

Institute of Immunology and Immunotherapy, University of Birmingham, UK

Introduction: Delivery of Tregs directly to the liver via ex-situ normothermic machine perfusion (NMP) avoids the need for cell signaling and migration within the circulation. Our aim was to determine if Tregs administered to the liver via ex-situ machine perfusion remain within the parenchyma, and maintain phenotype.

Methods: Human Tregs were isolated via flouresence-activated cell sorting and expanded. Two ex-situ machine perfusion models were utilized; a custom-built wedge perfusion model (WPM) that had an experimental and control lobe, and a whole liver perfusion model (Liver assist, XVIVO). Tregs were labelled with cell tracker red (CMTPX) prior to infusion and then administered via the machine perfusion circuit. CMTPX labelled Treg localization was assessed with confocal microscopy. After the perfusion, the perfusate was collected and the lymphocytes isolated. Mechanical dissociation of the liver tissue was performed and lymphocytes from within the tissue isolated. The suppressive phenotype (CD39, TIGIT, CTLA-4 expression) of the CMTPX labelled cells was assessed.

Results: Five WPM and two whole liver experiments were performed. Between 3-8x10 6 labelled Tregs were infused with the WPM and between 30-50x10 6 cells were infused into the whole liver model (Phenotype in figure A). Confocal microscopy identified the labelled Tregs within the parenchyma at the end of the wedge perfusion, and at 4 hours following infusion into the whole liver. The CMTPX positive Tregs obtained back the liver tissue and perfusate following infusion using the WPM (Figure B-E) demonstrated the expression of TIGIT and CTLA4 remained stable, however CD39 reduced.

Discussion: Tregs administered ex-situ appear to migrate from the vascular compartment and engraft into the organ, with minimal phenotypic change.

LIVER MACHINE PRESERVATION AT ROOM TEMPERATURE USING AN OXYGENATED, ACELLULAR PERFUSATE: A PILOT STUDY

KANHERE A, DANIEL D, BASTIAN J, BHATTACHARJYA R, BARNETT D, BHATTACHARJYA S

Transplant Surgery, University of Adelaide, South Australia

Introduction: Static Cold Storage (SCS) is the simple and cost-effective gold standard of liver preservation. Normothermic Machine Preservation (NMP) is emerging, but it is not widely used due to complexity and lack of long-term data. Oxygenated, acellular, machine perfusion at room temperature (IMP) is a novel method that aims to overcome the limitations of both its predecessors. The aim of this pilot study was to determine if IMP was feasible and non-inferior to SCS and NMP for deceased donor porcine livers.

Methods: Organs were retrieved from 12 pigs (mean weight 74.6kg) following ethics approval. Pigs were randomised into three preservation groups (n=4) and preserved for 5 hours. Metabolic activity was assessed by comparing arterial blood glucose (AGL) with hepatic venous glucose (VGL), and monitoring tissue ATP levels. Histology was scored by a blinded histopathologist, using a composite injury score derived from various hepatocellular characteristics.

Results and Discussion:

Figure 1: Biopsies were taken at regular intervals and frozen for ATP analysis. The graph shows that mean SCS ATP levels decreased from hours 1.5 to 5 of preservation, whilst increasing in IMP. A two-way ANOVA analysis yielded a P-value of 0.966 (p>0.05), suggesting no statistically significant difference.

Figure 2: The change from VGL exceeding AGL at 1-hour compared to AGL being higher than VGL at 5-hours suggests conversion from glycolytic to glycogenotic pathways in the liver.

In NMP, there was persistent anaerobic metabolism indicated by higher VGL throughout. No statistically significant difference was observed with p=0.33.

For the H&E histology, a score of 0-2 was considered mild damage, 3-5 moderate, and >6 severe. All three groups had a composite score between 0-2, suggesting mild damage at end-preservation. Once again, two-way ANOVA suggested no statistically significant difference between groups. These results indicate that IMP is indeed possible and appear non-inferior to SCS and NMP in liver preservation.

PHYSIOLOGICAL ASSESSMENT OF SMALL BOWEL GRAFT VIABILITY UNDER DIFFERENT EX VIVO MACHINE PERFUSION (EVMP) CONDITIONS

BASTIAN J, BHATTACHARJYA R, KANHERE A, DANIEL D, BARNETT D, BHATTACHARJYA S

Transplant Surgery, University of Adelaide, South Australia

Aims: To assess integrity of the physiological inter-relationships in the gastro – hepatic – pancreatic and small bowel axis during EVMP by measuring entero-insular response to luminal glucose stimulation as a marker of viability.

Methods: Eight large white pigs were ethically procured before random assignment to either normothermic blood EVMP (n = 4) or isothermic acellular EVMP (n = 4) groups. Abdominal blocks consisting of both kidneys, liver, pancreas and proximal 100cm of small bowel were surgically retrieved before integration into the MP rig. Luminal glucose stimulation tests were performed at two and four hours out of the allocated five hour preservation period. Serial venous glucose, GLP-1 and insulin readings were taken following stimulation. After five hours of preservation, fluorescein dye was injected into the circuit.

Results: A temporal response to glucose stimulation demonstrated sustained entero-insular axis physiology throughout normothermic blood and isothermic acellular EVMP. Mean GLP-1 post infusion for isothermic acellular EVMP was 122.4 pg/ml compared to normothermic blood EVMP at 82.14 pg/ml. Fluorescein angiography provided qualitative information of the vascular integrity of mesenteric arcades.

Conclusions : Maintenance of physiology is the best assessment for small bowel viability and EVMP offers the ability to bench test function in real time. The modified luminal glucose stimulation test is a feasible en-bloc method to compare EVMP quality under different conditions with the goal of improving efficiency and cost effectiveness of the process.

A BLUE PETER APPROACH TO MACHINE PERFUSION FOR ORGAN PRESERVATION

BHATTACHARJYA R 1 , BARNETT D 1 , KANHERE A 1 , BASTIAN J 1 , DANIEL D 1 , RUSZKIEWICZ A 2 , BHATTACHARJYA S 1

1 Transplant Surgery, University of Adelaide, 2 Pathology, University of Adelaide, South Australia

Aims: This study aimed to investigate whether it was feasible and cost-effective to convert a dialysis machine into an ex-vivo normothermic machine preservation device.

Methods: Composite abdominal organ blocks were retrieved from 12 beating heart porcine donors. Autologous whole blood was collected. Following a cold ischaemic period of 30 minutes, organ blocks were cannulated and connected to a Baxter Prismaflex TM Dialysis System and preserved for 5 hours. Oxygenated dialysate was pumped through the dialysate cartridge at 1500ml/hr and blood at 395ml/min. Serial blood gas samples were taken for assessment of blood oxygenation, oxygen consumption, carbon dioxide production and arterial pH maintenance. Plasma samples were taken for measurement of platelet-activating factor to assess reperfusion injury and hyperoxia.

Results: Oxygenation over the dialysis cartridge membrane achieved significantly higher PaO 2 as compared to room air oxygenation (p<0.05). Evidence of oxygen consumption and carbon dioxide production was observed, with a baseline approximately three times that of normal resting tissue oxygen consumption. The ability to control metabolic homeostasis was displayed through maintenance of arterial pH, and correction of venous pH abrogation. Quantitative platelet-activating factor measurement showed no statistically significant difference (p>0.05) as compared to the reference standard of static cold storage after 5 hours of preservation.

Conclusions: The successful conversion of a dialysis machine for organ preservation breaks down barriers to machine perfusion. A novel ability to dynamically control and correct homeostatic conditions was displayed. This opens the door to possibly improving the condition of organs ex vivo and to new therapeutic approaches.

THE Role of GASDERMIN D and PYROPTOSIS in acute kidney injury and long-term KIDNEY damage AFTER transplantation

SHAW K 1 , WANG YM 1 , LU B 1 , HU M 2 , CHUNG E 1 , ZHANG G 1 , LI J 2 , ROGERS N 2 , MCCARTHY H 1 , ALEXANDER S 1

1 Centre for Kidney Research, The Children’s Hospital at Westmead, Sydney, 2 Centre for Transplant and Renal Research, The Westmead Institude for Medical Research, New South Wales

Background: Gasdermin D (GSDMD) is a critical pore forming protein involved in pyroptosis, a highly inflammatory form of programmed cell death,. and may be involved in the pathogenesis of acute kidney injury (AKI) following ischemic reperfusion injury during kidney transplantation. This may potentially cause a rapid decline in renal function, fibrosis, and graft loss. Additionally, GSDMD-induced pore formation in the plasma membrane causes the release of pro-inflammatory cytokines, exacerbating tissue injury. GSDMD mutant mice derived by ENU mutagenesis at ANU have defective GSDMS function.

Aim: To investigate the role of pyroptosis in donor graft kidney injury using GSDMD mutant donor mice.

Methods: 8–12-week-old male GSDMD deficient mice (C57BL/6JANU-GSDMD M1ANU ) or C57BL/6 control mice were used as kidney donors for C57BL/6 recipient mice. The donor graft kidneys either underwent cold storage after saline perfusion on ice for 4 hours to replicate the effects of ischemia-reperfusion injury (IRI)-induced AKI or were transplanted immmediately.

Results: GSDMD deficient donor kidneys had better outcomes with GSDMD+ WT donor kidneys having significantly greater cell infiltrate (p<0.01) renal tubular damage (p<0.05) and glomerular damage (p<0.05) with a trend to greater fibrosis in the WT donor kidneys.

Conclusion: Pyroptosis plays a role in acute donor kidney injury associated with cold ischaemia time. The therapeutic targeting of GSDMD in donor kidneys to prevent injury may potentially limit kidney injury and improve donor graft outcomes.

SUCCESSFUL OUTCOMES FROM KIDNEY TRANSPLANTATION AFTER SIMULTANEOUS LUNG-KIDNEY TRANSPLANTATION- A SINGLE CENTRE EXPERIENCE

ENNIS S , PARASKEVA M, LEVVEY B, SHINGLES H, SNELL G

Lung Transplant Service, Alfred Hospital, Melbourne

Introduction Increasing numbers of lung transplant candidates have poor renal reserve which limits accessibility to life saving transplantation. This study analysed the outcomes of simultaneous lung kidney transplantation at single centre.

Methods: A retrospective single centre review of all patients ≥18 who underwent LTx between January 2010 and December 2023 at Alfred Health, Melbourne, Australia. We identified a total of 11 simultaneous lung-kidney transplantations (Table 1). All patients had been co-managed by the Lung Transplantation Service and Department of Renal Medicine at The Alfred Hospital. We recorded and analysed patient’s demographics, donation type, complications and clinical outcomes including lung and renal allograft function and compared these to the lung transplant only group. The study was approved by The Alfred Hospital Ethics Committee.

Results: A total of 11 patients underwent simultaneous deceased donor lung-kidney transplantation out of a total of 1043 lung transplantations. Median age was 46 years (38-59), with a slight female predominance (58%). Indications for combined lung-kidney transplantation are included in Table 1. Median survival was not different between the lung-kidney and the isolated lung transplant group [1239 (231-1987) vs. 1703 (729-2774) days (p=0.24)]. Maximum forced expiratory capacity achieved by 12 months was not significantly different between groups (p=0.15), (Table 2).

Conclusion: Simultaneous lung kidney transplantation is a possible strategy for patients with combined end stage lung and kidney disease, which is associated with longer post operative intensive care stay but comparative and acceptable overall survival and lung function and 12 months.

Table 1: Patient Characteristics and Clinical Information: Simultaneous Lung-Kidney Transplantation (LTx-KTx) compared to all Lung Transplants

DO THE ORGANMATCH NON-RENAL MATCHING ALGORITHMS IDENTIFY COMPATIBLE RECIPIENTS FOR TRANSPLANT?

SCAMMELL R , WATSON N, HOLDSWORTH R

Transplantation Immunology Laboratory, Lifeblood-National OrganMatch Office New South Wales

Aims: In 2022 the Kidney/Pancreas, Lung and Heart matching algorithms were developed in conjunction with the transplant advisory committees for each of the organs. These algorithms were implemented in OrganMatch in September 2022, December 2022 and February 2023 respectively and were developed to produce an initial list of potential recipients for the transplant units to evaluate for selection for transplant. Implementation of the algorithms aimed to enhance the existing process for selection of recipients when crossmatched with deceased organ donors and facilitate a more efficient process for issuing VXM results.

A review of the deceased donors from 2023 was performed to identify the recipients that were excluded for matching by the algorithm but still received a transplant from the non-matched donor. This allowed assessment of the success of the non-renal algorithms to identify the recipient that was transplanted.

Method: Australian Deceased donors in 2023 were reviewed and the recipients that received a Kidney/Pancreas, Heart or Lung transplant were identified. For these recipients, the matching algorithms were reviewed to determine if the algorithm included them. If they were excluded by the algorithm further investigation was undertaken as to the reason.

Note the Heart Algorithm was implemented in February 2023 so the data for heart recipients in January 2023 was excluded.

Results:

Conclusion: The non renal matching algorithms have been successful in identifying the compatible transplanted recipient 94% of the time (716 out of 762 cases) in 2023.

The matching algorithms are working as expected. There still needs to be flexibility for the transplant units to select recipients outside the algorithm due to exceptional circumstances which would account for the 6% of cases.

MICROBIAL DIVERSITY. ANTIBIOTIC PROPHYLAXIS AND THEIR INFLUENCE ON TIME TO EXTUBATION IN LUNG TRANSPLANT RECIPIENTS

TADJKARIMI J , RANCE J, SITHAMPARANATHAN S, CHOE EH

Lung Transplant Service, Auckland City Hospital, New Zealand

Aims: To identify microbial diversity of donor lungs via donor bronchial swabs (DBS) and recipient posttransplant bronchial washings (BWs). Assess whether Lung Transplant Recipients (LTR) received appropriate antibiotic prophylaxis based on swabs and washings, and explore correlation between culture positivity, initial antibiotics and ICU stay.

Methods: A Retrospective analysis of 83 consecutive LTR at Auckland City Hospital documented baseline demographics, initial antimicrobial choice & positive microbiology results with primary outcomes being time to extubation and ICU length of stay (LOS).

Results: 66% of DBS were culture positive, with a trend seen in longer extubation times compared to negative culture donors. Methicillin-susceptible Staphylococcus aureus accounted for 46% of DBS whilst Gram Negative Organisms (GNOs) were recorded in 19%. The most chosen antibiotic was Cefazolin, and antibiotic prophylaxis was deemed appropriate in 83% based on DBS. Post-transplant BWs were performed in 51% of LTR at a mean of three days post-transplant; GNOs were identified on 40% of samples. This group exhibited a trend towards longer extubation times (168 vs 96 hours p=0.265) and significantly longer LOS compared to LTR without GNOs (24 vs 9 days p=0.022) [Figure 1]. Of the positive BWs, 32% exhibited insufficient coverage with initial antibiotic prophylaxis, resulting in significantly longer ICU LOS (33 vs 11 days, p=0.026).

Figure 1

Conclusions: Initial antibiotic choice remained appropriate based on DBS. GNO growth trended towards longer extubation times and significantly longer LOS. Colonisation and infection with new nosocomial GNOs occurred early in the post-transplant period. Prompt bronchial washings could help guide appropriate antimicrobial therapy, thereby reducing time to extubation and ICU LOS.

EVALUATING THE ACCURACY OF ANZDATA RECORDED CAUSE OF DEATH AMONGST TRANSPLANT RECIPIENTS

LEVY M 1 , SINDONE J 2 , DENNIS M 2 , PURANIK R 2 , CHADBAN S 1 , YING T 1

1 Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, 2 Royal Prince Alfred Hospital, Sydney

Aim: To determine the accuracy of cause of death (COD) recorded by ANZDATA, by assessing concordance with blinded clinicians.

Methods: Kidney transplant recipients (KTR) transplanted and managed by Sydney Local Health District clinicians until their death were studied. Pre-death medical data was extracted from clinical records and provided to a consultant panel. Primary and secondary causes of death were determined by 3 nephrologists and 2 cardiologist independently. Cohens Kappa statistic was calculated to assess concordance with the cause of death recorded on ANZDATA.

Results: Between 2010 – 2020, 121 patients met inclusion criteria. Mean age at death was 63 years, 60.5% were male, and 77.6% were deceased donor recipients. 76 (63%) had clinical information relating to their death available. Agreement for the primary cause of death was moderate (52%, kappa 0.466) and was highest for cancer (88.2%). The greatest discrepancy related to ‘withdrawal’ or ’CKD’ which accounted for 13.2% of deaths in ANZDATA and 5.3% of deaths on panel assessment. Cardiovascular, cancer and infection each comprised 30% of clinician-adjudicated primary causes of death, compared to 35%, 23% and 16% respectively on ANZDATA over a similar time frame. The most common secondary cause of death was infection, which was a contributing factor in 47.8% of cardiovascular and 60.8% of cancer deaths.

Conclusion: Death in a KTR is often complex with multiple contributing causes. Given only moderate agreement between ANZDATA recorded and clinician-adjudicated primary COD, recording contributing causes of death may improve the accuracy and quality of data in the ANZDATA registry.

LUNG TRANSPLANTATION FOR SHORT-TELOMERE INTERSTITIAL LUNG DISEASE: OUTCOMES FROM AUSTRALIA

ZHANG L , LUTZSKY V, APTE S, GROVES P, TAN M, WATSON S, HOPKINS P, CHAMBERS D, MACKINTOSH J

Lung Transplant Service, Prince Charles Hospital, Brisbane

Introduction Lung transplantation outcomes in patients with short-telomere interstitial lung disease (ILD) are presently conflicting. We sought to characterize the demographics and outcomes of an Australian cohort of short-telomere patients undergoing lung transplantation for ILD.

Methods: We performed a single-centre retrospective cohort study. We included all lung transplant recipients at the Queensland Lung Transplant Service, Australia, whom had had their peripheral blood telomere length measured via Flow-FISH and had undergone transplantation for ILD.

Results: A total of 52 lung transplant recipients were included, with 31 patients (59.6%) demonstrated to have a short telomere length (defined as peripheral blood telomere length equivocal to or below the 10 th centile). Short-telomere recipients were demographically similar to normal-telomere recipients, with no significant difference in age at time of transplant, gender, or underlying pre-transplant ILD diagnosis. Short telomere length was not found to be associated with shorter time to any cytopenia, shorter time to clinically significant neutropenia (defined as neutrophil count <1.00 and/or requiring granulocyte colony stimulating factor), or cytomegalovirus viremia. Additionally, telomere length was not associated with either duration of cytopenia or duration of significant neutropenia post-transplant. No significant difference in time to chronic lung allograft dysfunction (CLAD) or death was found in short-telomere recipients compared to recipients with normal telomere length.

Conclusion: In our single-centre Australian cohort, within the limits of sample size, short-telomere patients undergoing lung transplantation for ILD had similar outcomes to those with normal telomere length, with similar rates and severity of post-transplant bone marrow suppression and overall CLAD-free survival.

HOW BIG IS OUR BLIND SPOT? ESTIMATING THE BURDEN OF ORGAN FAILURE UNMET BY TRANSPLANTATION IN THE USA

MCMICHAEL L 1 , SRIDHAR V 2 , LOPEZ R 3 , LEVINE D 4 , TEUTEBERG J 5 , VERNA E 6 , SCHOLD J 3 , GILL J 7

1 Central Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, 2 Department of Nephrology, University Health Network, 3 Department of Medicine, University of Colorado, USA, 4 Stanford Lung Transplant Program, Stanford Medicine, USA, 5 Department of Cardiovascular Medicine, Stanford Medicine, USA, 6 Center for Liver Disease and Transplantation, Columbia University, USA, 7 Department of Nephrology, University of British Columbia, Canada

Aim: Solid organ transplantation is highly valued by patients and society. Questions have been raised whether the current transplant system is fit to serve the needs of organ failure patients. We sought to identify the number of patients who may be eligible for solid organ transplantation and compare this to the transplant waiting list.

Methods: Patients registered in the National Readmissions Database (NRD) and Scientific Registry of Transplant Recipients (SRTR) between 2016-2019 were included. Patients potentially eligible for solid organ transplantation were identified in the NRD by hospital discharge coding identifying organ failure and absence of transplant contraindications. We compared the number of potentially eligible patients with patients waitlisted for transplantation.

Results: The estimated population size of eligible solid organ transplant patients in the United States was a yearly average of 142,158 heart, 37,419 lung, 126,536 liver and 181,548 kidney failure patients, figure 1. The organ transplant waiting list represented 5% of heart, 9% of lung, 19% of liver and 64% of kidney failure patients. Younger patients, men, privately insured patients, and metropolitan patients were more likely to appear on the waiting list.

Conclusion: The burden of organ failure is not captured by the solid organ transplant waiting list and should not be used to estimate demand for transplantation. Moves to accurately identify and track patients with organ failure before they enter the organ transplant waiting list are required. This will support improved understanding of the patient experience, monitor system performance, and ensure appropriate allocation of system & research funding.

Figure 1 – Prevalent patients waitlisted for solid organ transplantation as a proportion of estimated organ failure population size between 2016-2019, by organ group.

ANTI-INTERLEUKIN-6 ANTIBODY TREATMENT IS PROTECTIVE IN A MOUSE MODEL OF KIDNEY ISCHEMIA-REPERFUSION INJURY

BONGONI A 1 , MCRAE J 1 , SALVARIS E 1 , FISICARO N 1 , BIONDO M 2 , ROWE T 2 , BAZ MORELLI A 2 , COWAN P 1,3

1 Immunology Research Centre, St Vincent’s Hospital, Melbourne, 2 CSL Ltd Melbourne, CSL Ltd Melbourne, 3 St Vincent’s Hospital Melbourne, Department of Medicine, Victoria

Background. Ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI) in a variety of settings, including kidney transplantation. There are currently no effective clinical therapies for IRI. Inflammation and tubular cell apoptosis are important in the pathophysiology of IR-induced renal dysfunction and progressive chronic kidney disease. Interleukin (IL)-6 is a pleiotropic cytokine that regulates immune responses, and IL-6 blockade is under investigation as a treatment for chronic antibody-mediated rejection. However, IL-6 blockade has produced mixed results in attenuating renal IRI/AKI.

Aim: To test ALD518, an anti-IL-6 monoclonal antibody, in a mouse model of warm renal IRI.

Methods: Male 10-12 week old C57BL/6 mice underwent right nephrectomy followed by clamping of the left renal pedicle for 22 min (IRI), or nephrectomy only (Sham). Mice (n=8/group) were treated with 40 mg/kg ALD518 or isotype-matched control, either i.p. 30 min pre-ischemia or i.v. immediately post-ischemia. Mice were sacrificed 24 hrs after reperfusion, and blood and kidney samples were collected to assess renal function (serum creatinine, urea), complement activation (plasma C5a) and deposition (C9), and cellular infiltration.

Results: IR caused significant kidney injury and inflammation indicated by increased serum creatinine, urea, complement activation/deposition, and cell infiltration, as compared to sham control. Treatment with ALD518 preserved kidney function and reduced complement activation and cellular infiltration.

Conclusion: ALD518 significantly protected against kidney IRI when given before or after IR, indicating that IL-6 blockade is a promising approach to attenuate IRI in kidney transplantation.

WHOLE BLOOD VERSUS PLASMA TACROLIMUS TROUGH CONCENTRATIONS DURING PREGNANCY AND THEIR IMPACT ON OUTCOMES

SALLUSTIO B 1 , ALONGE M 1 , COLLER J 2 , REUTER S 3 , HEWAWASAM E 4 , JESUDASON S 5

1 Department of Clinical Pharmacology, Basil Hetzel Institute, South Australia, 2 School of Biomedicine, University of Adelaide, 3 Department of Clinical and Health Sciences, University of South Australia, 4 ANZDATA, South Australian Health and Medical Research Institute, 5 Central Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital

Aims: Whole blood trough concentrations (WBC 0 ) of tacrolimus (Tac) are unreliable in pregnant women due to physiological changes in unbound Tac and may underestimate exposure, leading to overdosing. We aimed to determine if plasma trough Tac concentrations (PC 0 ) may be a better measure in pregnant kidney transplant recipients.

Methods: We developed and utilised a new assay to measure Tac PC 0 and compared it with WBC 0 , and their impact on maternal and neonatal outcomes.

Results: Of 9 participants (6 kidney transplants, 3 lupus nephritis), 6 experienced pregnancy-related hypertensive disorders. Six babies (75%) were born preterm (<37 weeks gestation) and five (83%) had low birthweights (<2500g). Median (range) WBC 0 (n=97) and PC 0 (n=88) were 5400 (1600-23100) and 880 (275-4270) ng/L, respectively. WBC 0 and PC 0 had a positive association (R 2 =0.51; p<0.001), with PC 0 approximately 15% of WBC 0 . The PC 0 /WBC 0 ratio correlated with albumin (p<0.05) and trimester (p<0.01). It was higher during pregnancy, consistent with a trend for higher or unchanged PC 0 (p=0.07) and lower WBC 0 during pregnancy (Fig 1). Higher maternal serum creatinine was associated with dose (p<0.05) and trimester (p<0.001). Mean infant birthweight decreased by 60 g (95% CI: 90-30; p<0.0001, adjusted p<0.001) or 223g (95% CI: 442-23g; p=0.03, adjusted p>0.05) for every 100 ng/L increase in WBC 0 or PC 0 , respectively. WBC 0 was also associated with gestational age (p=0.03, adjusted p>0.05). There was no association between other maternal outcomes and WBC 0 or PC 0 .

Conclusions: PC 0 may be an alternative measure in pregnant kidney transplant recipients.

Fig 1. Changes in whole blood versus plasma tacrolimus concentrations from pre-pregnancy to post-partum.

SHORT-TERM MACHINE PRESERVATION AT ROOM TEMPERATURE IS NOT INFERIOR TO STATIC COLD STORAGE FOR DECEASED DONOR KIDNEYS

BARNETT D , BHATTACHARJYA R, KANHERE A, DANIEL D, BASTIAN J, BHATTACHARJYA S

Transplant Surgery, University of Adelaide, South Australia

Aims: This study aimed to establish whether short-term machine preservation with acellular oxygenated perfusate at room temperature (IMP) is inferior to SCS for deceased donor kidneys in a large animal model.

Methods: Following local ethics approval, organs were retrieved from 8 adult female Landrace pigs (mean 74.6kg) using a novel en-bloc technique. 8 kidneys were preserved with SCS and 8 with IMP for 5 hours as part of a multi-visceral block. Core biopsies were taken at 90-minute intervals, snap-frozen and stored at -80°C. ATP from core biopsies was extracted using a validated boiling water extraction method2 and measured using a luciferase bioluminescent assay (FLAA, Sigma-Aldrich) with a TD-20/20 luminometer (Turner Designs). A two-way ANOVA test was conducted with significance set at p<0.05. Blinded histological analysis by an expert histopathologist was performed on biopsies using a novel scoring system for evidence of preservation-related ultrastructural damage.

Results: Baseline ATP levels were 3.21x10 -10 mol in the SCS group, compared to 1.58x10 -10 mol for IMP. During preservation, the ATP concentration rose in the IMP group to 2.49x10 -10 mol. The ATP levels in SCS remained relatively stable during preservation reaching 3.96x10 -10 mol after 5 hours. A two-way ANOVA test of ATP levels after preservation was conducted, yielding a P-value of 0.37, indicating no significant statistical difference, thus implying non-inferiority. Histopathological scores were identical between groups.

Conclusions: IMP is non-inferior in preserving cellular ATP levels compared with SCS. More work is required to demonstrate if these findings correlate to improved organ function following transplant.

5-YEAR GRAFT SURVIVAL AND INCIDENCE OF CMV AND BK VIREMIA IN KIDNEY TRANSPLANTATION IN CENTRAL AUSTRALIA

MASCARO J 1 , ULLAH S 2 , SAJIV C 3 , THOMAS S 3

1 Department of Nephrology, Western Health, 2 School of Public Health, Flinders University, Adelaide, 3 Department of Nephrology, Alice Springs Hospital, Northern Territory

Aim: To explore the relationship between induction agents, cytomegalovirus (CMV) and polyomavirus (BK) viremia rates and its effect on graft survival in renal transplant recipients from 1980 to 2021. To examine if First Nations Australian status was a risk factor for CMV or BK viremia post-renal transplant in Central Australia, which has a large population of high-risk transplant patients.

Background: First Nations Australians experience elevated infection and graft failure rates post-renal transplant. Research gaps exist, especially concerning Anti-thymocyte Globulin (ATG) as an induction agent and its impact on CMV/BK viremia rates and graft survival in remote Australia.

Method: This single-centre retrospective cohort study included 101 renal transplant patients categorised into pre-2015 and post-2015 groups based on the induction agent used.

Results: CMV viremia significantly increased post-2015, with ethnicity as an independent risk factor for CMV viremia in First Nations Australians. While BK viremia was higher post-2015 and among First Nations Australians, statistical significance was not observed. Multivariate analysis showed no independent association of CMV/BK viremia with increased graft loss. However, 5-year graft survival significantly improved post-2015, supporting continued ATG use in high-risk and First Nations Australian populations.

Conclusion: Although higher CMV and BK viremia rates were observed post-2015, only CMV infections were significant. First Nations Australian status was a CMV viremia risk factor, but both CMV and BK viremia did not significantly impact 5-year graft survival. Increased 5-year graft survival post-2015 supports ongoing ATG use in high-risk populations, underscoring the need for further research into post-renal transplantation viremia screening and treatment.

A MULTICENTRE RANDOMISED TRIAL OF DIETARY INULIN TO IMPROVE SARS-COV-2 VACCINE RESPONSE IN KIDNEY TRANSPLANT RECIPIENTS

SINGER J 1 , TUNBRIDGE M 2 , PERKINS G 3 , SALEHI T 2 , GRUBOR-BAUK B 3 , SIM B 2 , CHAI CS 3 , YING T 1 , COATES PT 2 , CHADBAN SJ 1

1 Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, 2 Central Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, 3 Adelaide Medical School, Faculty of Health and Medical Sciences University of Adelaide

Aim: Kidney transplant recipients (KTR) are at an increased risk of hospitalisation and death from SARS-CoV-2 infection, and standard 2-dose vaccination schedules are typically inadequate to generate protective immunity. The gut microbiota has been shown to modulate vaccine responses with short-chain fatty acid (SCFA) producing species and dietary-fibre intake associated with heightened vaccine immunogenicity. With dysbiosis common in KTR, augmentation of microbiota-derived SCFAs through pre-biotic fibre supplementation is an attractive adjuvant strategy to improve vaccine-induced immunity.

Methods: We conducted a multicentre, double-blinded, placebo-controlled trial. 72 KTRs with an inadequate response (anti-RBD <100U/mL) to a standard 2 dose COVID-19 mRNA vaccine schedule were randomized to dietary inulin (20g/day) or placebo. The intervention commenced 4-weeks before the 3 rd mRNA COVID vaccine dose and continued for a further 4-weeks after. Vaccine specific humoral and T-cell responses, and 16s-rRNA sequencing of the faecal metagenome were conducted 4-weeks post-3 rd vaccine dose.

Results: Participants were male (51/72, 71%), age 58 ± 11 years (mean/SD), 7.9 [2.5 – 13.9] years post-transplant (median/range), with eGFR 56.1 ± 25.9 ml/min (mean/SD), with no significant differences between groups. Prebiotic inulin was feasible, tolerable, and safe, but did not significantly boost vaccine specific immune responses (Fig 1A). Inulin supplementation resulted in a significant increase in SCFA-producing bacteria (2.3-fold increase in Bifidobacterium spp., Fig 1B, p<0.02) and predicted metabolic pathways.

Conclusion: Pre-biotic fibre supplementation is a feasible and effective strategy to enhance the gut microbiota in KTRs and warrants further investigations as an adjuvant to enhance vaccine-induced immunity.

Figure 1

HISTOLOGICAL COMPARISON OF PANCREAS PRESERVED BY MACHINE PERFUSION AND STATIC COLD STORAGE

DANIEL D 1 , BHATTACHARJYA R 1 , BASTIAN J 1 , KANHERE A 1 , BARNETT D 1 , RUSZKIEWICZ A 2 , BHATTACHARJYA S 1

1 Transplant Surgery, University of Adelaide, 2 Pathology, University of Adelaide

Aims: This study aimed to investigate whether machine-preserved DBD pancreata had significant changes in histology as compared to the gold standard of static cold storage.

Methods: 12 porcine pancreata were retrieved, equally separated into isothermic machine perfusion with an acellular perfusate, normothermic machine perfusion with autologous whole blood and static cold storage groups and preserved ex-vivo for 5 hours. Transplantation was simulated in a reperfusion model at body temperature with a modified cardiopulmonary bypass rig. Core tissue samples were obtained at retrieval (A), post-preservation (F) and post-reperfusion (H), fixed in formalin and H&E stained. Blinded histological analysis was conducted by a senior pathologist and scored using a novel scoring system taking into account acinar cell autolysis, fat necrosis, duct epithelium damage and islet cell damage.

Results: A composite score was obtained from each sample and categorised based on the extent of damage. Total scores were average at each time point for each organ (Table 1) and compared using a two-way ANOVA test. No significant difference was observed between any of the three groups (p>0.05).

Conclusions: The feasibility of isothermic preservation for pancreata was displayed. No statistical difference between isothermic perfusion and static cold storage implied non-inferiority. The findings also imply that temperature control and blood as a perfusate are not requirements for machine perfusion.

Table 1:

IMPLEMENTING A VALUES-DRIVEN POLICY IN A COMPLEX SYSTEM: WHAT HAPPENED WHEN DEEMED CONSENT WAS IMPLEMENTED IN ENGLAND?

MC LAUGHLIN L 1 , NOYES J 1 , AL-HABOUBI M 2 , O’NEILL S 2 , WILLIAMS L 2 , BOSTOCK J 2 , BOADU P 2 , MAYS N 2

1 School of Medical and Health Sciences, Bangor University, 2 Policy Innovation Research Unit, London School of Hygiene and Tropical Medicine, UK

Aim: In May 2020, England implemented an ‘opt-out’ system of consent, on the basis that switching the default to one more closely aligned with the in-principle preferences of citizens would make deceased organ donation easier.

Method: A mixed-methods evaluation comprising review of Parliamentary debates, surveys and interviews with healthcare professionals; interviews with the public and donor families; analyses of public attitude surveys and donor audit data; and patient and public involvement.

Results: Implementing a ‘soft’ opt-out system into a well-established and complex opt-in system has been challenging. Consent forms, procedures and audits have become more complicated. Specialist nurses have to move between scenarios with families where opt-out applies, and others where family consent (opt-in) is still required. Bereaved families still think they are the decision makers. There is an (increasing) mismatch between someone establishing their wishes on the organ donor register and what the family are asked after death. Support for organ donation continues to vary between subgroups of the population. Implementation created a context for mis/disinformation to spread, especially among minority ethnic and faith groups. Consent rates fell following implementation and have not recovered since the pandemic which also hampered ability to assess the effectiveness of the law change.

Conclusion: The legacy of informed consent has meant that the principle behind the Act that everybody is a potential donor has yet to be realised. Rather than relying on opt-out legislation, other ways are likely to be more effective in improving the organ donation system.

Utility and therapeutic implications of Pharmacogenomic testing in kidney transplant recipients (KTR)

HO S , SWAMINATHAN R, JAMBOTI J, ABRAHAM A, PUTTAGUNTA H, IRISH A

Nephrology and Renal Transplant, Fiona Stanley Hospital, Western Australia

Introduction: Pharmacogenomics plays a role in determining the therapeutic effect of medications due to the genetic polymorphism of drug metabolising enzymes. Poor, intermediate or rapid metaboliser phenotypes have differing metabolic capabilities which impact on drug kinetics. As a result, drug exposure varies between phenotypes and uniform dosing may not be appropriate. Guidelines for tailored dosing are available for certain drug-phenotype pairs to enable optimisation of drug levels. Identification of these, at risk or actionable phenotypes, is of interest in renal transplantation, where tacrolimus concentrations are associated with graft outcomes.

Aim: To assess incidence of actionable phenotypes in KTR and to identify presence of phenotypes associated with altered tacrolimus pharmacokinetics.

Method: Pharmacogenomic screening was conducted in 10 KTR including CYP 3A4/5 genetic testing relevant to tacrolimus metabolism.

Results: A total of 28 actionable phenotypes were detected in 10 screened patients. All 10 had ≥1 actionable phenotype, 90% had ≥ 2 and 40% had ≥ 3, with drug-gene interactions identified for cardiovascular, analgesic and antidepressant medications (refer Table 1). Two of ten patients were CYP3A5 intermediate metabolisers. This phenotype is associated with enhanced tacrolimus clearance, lower troughs and increase risk of rejection with guidelines recommending a 1.5 to 2 fold increase in tacrolimus dosing. Those identified were observed to require higher doses (3.8x) to achieve therapeutic levels and took twice as long for target attainment (7 vs 3.5 days).

Conclusion: Pharmacogenomic screening of KTR has clinical utility in the identification of actionable metaboliser phenotypes who would benefit from tailored dosing of medications, including tacrolimus.

DECISION SUPPORT TOOL TO AID RISK ASSESSMENT OF ACCEPTING VERSUS DECLINING A KIDNEY OFFER FROM A DONOR WITH A HISTORY OF CANCER

HEDLEY J 1 , WHITE S 1 , MUSCAT D 2 , WYBURN K 3 , WEBSTER A 1

1 Collaborative Centre for Organ Donation Evidence (CODE), Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, 2 Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, 3 Renal Unit, Royal Prince Alfred Hospital, Sydney

Background: The decision to accept a kidney offer from a donor with cancer history involves complex assessment of the risk of acceptance versus remaining on dialysis. Transplant clinicians and patients would benefit from tools to aid this decision-making.

Aims: To develop a decision support tool for patients and clinicians comparing consequences of accepting versus declining a kidney offer from a deceased donor with reported cancer history.

Methods: Using data from ANZDATA/ANZOD to model time to transplant (Weibull) and graft failure (2-knot spline). Mortality and cancer incidence were based on life tables (ABS, Stats NZ), AIHW, and published literature. We adjusted for age, sex, blood-group, previous transplants, comorbidities, kidney disease, dialysis time, kidney failure time, and donor characteristics (age, sex, pathway, KDPI, cancer). Transmission risk by cancer site and type was based on TSANZ guidelines. A tool interface was developed using the R package ‘shiny’.

Results: A web-app visualising expected outcomes (Figure 1). For example, for a hypothetical donor (45y, male, DBD, KDPI 31%, glioblastoma) and recipient (50y, male, blood-group O, NSW resident, glomerular disease, transplant-naive, 2-years’ dialysis) and the estimated risk of cancer transmission is 2%. If declined, median time to next transplant is 2.2 years, with a risk of death (12%) or cancer (1.3%) in that time. Without transmission, median graft survival is 22.4 years versus 18.9 years if transplanted from an average donor in 2.2 years.

Conclusions: A bespoke visualisation of expected transplant outcomes and risks of remaining on dialysis may enable informed decision-making and better patient outcomes.

Figure 1: Screenshot of the decision support tool for a hypothetical patient and donor with cancer

A PILOT RANDOMISED CONTROLLED TRIAL OF ADVANCED RECOVERY ROOM CARE POST LIVING DONOR KIDNEY TRANSPLANTATION

VENKATARAMAN K 1 , COLLINS M 1,2 , LUDBROOK G 1,2 , COATES T 2

1 Faculty of Health and Medical Sciences, University of Adelaide, 2 Central Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital

Background: Significant variation exists between hospitals in how kidney transplant patients are managed in the immediate post-operative period, with post-operative care settings including intensive care units, high dependency units and renal wards. No comparative data exists to inform practices. Advanced Recovery Room Care (ARRC) is a model of post-operative care that provides a high dependency unit level of care.

Methodology: We conducted a single-centre pilot open-label randomised controlled trial (ACTRN12622001093774), randomising live donor kidney transplant recipients 1:1 to either post operative care in the ARRC or to standard of care management on the renal ward. The intervention involved closer haemodynamic monitoring, more frequent medical officer review and the ability to assess and address post operative hypotension with fluids and vasopressors. The primary outcomes were 1) safety (adverse events in the first 28 days post transplantation), 2) recruitment feasibility and 3) episodes of hypotension between groups.

Results: 27 living donor transplants have been performed during the study to date; 18 recipients were eligible for enrolment into the trial. A total of 14 participants underwent randomisation (Figure 1). There were no major adverse events in either arm. 4 out of 7 participants (57%) were hypotensive post operatively in the control arm compared to 1 out of 7 participants (14%) in the intervention. The trial is ongoing.

Conclusion: In this pilot trial, use of advanced recovery room care was safe, and recruitment into a larger clinical trial appears feasible. Advanced recovery room care may reduce the incidence of post-transplant hypotension.

Figure 1: Consort diagram

LIVING DONOR DEMOGRAPHICS IN AUSTRALIA: HAVE DISPARITIES INCREASED OVER TIME?

SCARLATO R 1 , DE LA MATA N 2 , CLAYTON P 3 , TEKITEKI A 4 , WYBURN K 1 , WYLD M 5

1 Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, 2 School of Medicine, Faculty of Health Sciences, University of Sydney, 3 ANZDATA, Royal Adelaide Hospital, 4 Department of Renal Medicine, Auckland City Hospital, New Zealand, 5 Renal and Transplantation Unit, Westmead Hospital, Sydney

Aims: Australia has fewer living donors (LD) now than it did 10-15 years ago, while New Zealand (NZ) has seen continued growth. It was hypothesised over time the LD population has become more concentrated in relatively privileged groups, particularly in Australia. We aimed to assess changes over time in Australian and New Zealand LDs ethnicity, sex, age, and socio-economic position (SEP).

Methods : Using the Australian and New Zealand Living Kidney Donor Registry, we included all living donors in Australia and New Zealand (2004-2021). We used Poisson, logistic, and linear regression to analyse change over time in donor demographics.

Results: Of the 5772 living donors, 4562(79%) were from Australia and 1209(21%) from NZ. Mean age at donation was 50±11yrs in Australia and 46±12yrs in NZ (p<0.001). In Australia donors were typically female (57%), Caucasian (84%), and SEP privileged (28% in top 3 deciles). Over the study period Australian donors became older (p<0.001), more socio-economically advantaged (p<0.001), and less likely to be First Peoples (p<0.001). Females continue to be the majority of donors, with no change over time (p=0.83). In NZ, donors were also typically female (59%), Caucasian (75%). Over time there was no difference in sex (p=0.63) or age (p=0.53), but an increase in Māori donors (p=0.027) in NZ.

Conclusion: Inequities in the living donor population have increased over time in Australia. Compared to the 2004-2009 era, donors are more likely to be older and economically privileged, and less likely to be First Peoples (Australia). In NZ Maori donors have increased.

TRANSCRIPTOMIC ANALYSIS IDENTIFIES AIM2 INFLAMMASOME GENE SIGNATURE IN BK POLYOMAVIRUS ASSOCIATED NEPHROPATHY

DAVIDSON L 1 , ROWLANDSON M 2 , MUANG MYINT T 2 , HIBBERD A 2 , HEER M 3 , HORVAT J 1 , NIESSEN N 1 , HSU A 1 , REID A 1 , MAYALL J 1 , TREVILLIAN P 1 , BAINES K 1

1 Immune Health, Hunter Medical Research Institute, Newcastle, 2 Hunter Transplant Research Foundation, John Hunter Hospital, Newcastle, 3 Renal Transplant Unit, John Hunter Hospital, Newcastle, New South Wales

Aims: BK polyomavirus (BKPyV) is the most common viral infection experienced by kidney transplant recipients and can lead to the development of BKPyV-associated nephropathy (BKPyVAN). This study aims to identify validated gene expression signatures, networks and pathways underlying BKPyVAN.

Methods: Publicly available datasets GSE47199 , GSE72925 and GSE75693 were downloaded into GeneSpring GX software and differentially expressed genes (adjusted p<0.05 and fold change>2) across all 3 datasets were identified. Protein interaction networks were investigated using STRING and predictive ability assessed using multiple regression, receiver operating characteristic (ROC) curves and area under the curve (AUC).

Results: The comparison of BKPyVAN and stable graft function patients unveiled a total of 1239, 827 and 620 differentially expressed genes that were identified from GSE47199 , GSE72925 and GSE75693 gene sets, respectively. There were 136 genes that met our criteria of differential expression across the 3 datasets. From these genes, we identified 4 protein interaction networks, involving 1) complement activation (e.g.C1Qs, C2), integrins (e.g.ITGAL, ITGB2), T cell receptors (e.g.CD8B, CD3D); 2) T/NK cell killing and cytolysis (GZMs, GNLY, PRF1); 3) inflammasome (AIM2, CASP1, PYCARD, CARD16); and 4) chemokines (e.g.CXCL9, CXCL10), and interferon signalling (e.g.IRF1, STAT1). The AIM2 inflammasome 4 gene signature was able to predict BKPyVAN from stable with 94% accuracy (p<0.001; GSE72925 ) and 87% accuracy (p<0.001; GSE75693 ).

Conclusions: Transcriptomic analysis of kidney tissue enables identification of novel biomarkers, mechanisms, and therapeutic targets for BKPyVAN. Further studies are warranted in investigating the AIM2 inflammasome as well as signatures distinct from rejection pathologies in larger sample cohorts.

UTILITY OF 6 AND 12 MONTH SURVEILLANCE BRONCOHSCOPY WITH TRANSBRONCHIAL LUNG BIOPSY IN LUNG TRANSPLANT RECIPIENTS

GADSBY B , DIVITHOTAWELA C, HOPKINS P

Lung Transplant Service, Prince Charles Hospital, Brisbane

Aims: We aimed to assess the utility of surveillance bronchoscopies (SBs) performed in lung transplant recipients (LTRs) in terms of the benefit of detecting and treating occult acute rejection (AR) in relation to developing chronic lung allograft dysfunction (CLAD) and improving overall survival and the risk of procedural related complications.

Methods: We conducted a single institution retrospective analysis evaluating 118 adult patients who received bronchoscopies within the first 12 months following lung transplantation (LTx) at The Prince Charles Hospital between January 2018 and January 2023. The data collected included baseline characteristics, bronchoscopy results, and complications. The protocols for immunosuppression, bronchoscopy, and grading and treatment of acute rejection were standardised.

Results: Over the five-year period, there were 456 SBs performed. The rate of AR detected on SBs was 10.5%. Of this, 8.1% was detected within the first three months compared with 1.9% beyond three months, and 98% of AR was graded as minimal to mild severity, with an average A and B score of 1.38 and 0.15 respectively. Each patient had an average of 2.8 additional bronchoscopies performed during the first 12 months. The rate of significant bleeding was 2.2% and pneumothorax was 1.1%. The overall survival rate was 83.6% and the CLAD free survival rate is under analysis.

Conclusions: At our service, we found that the rate of occult AR detected on SBs was low beyond three months. We have not yet determined whether the detection and treatment of occult AR improves CLAD free and overall survival but this is of importance given bronchoscopy is not a risk free procedure.

ADDRESSING QUALITY-OF-LIFE AFTER PAEDIATRIC LIVER TRANSPLANTION. CO-DESIGNING PRACTICE CHANGE TO IMPROVE OUTCOMES

HOLMES K

Gastroenterology and Clinical Nutrition, The Royal Children’s Hospital Melbourne

Paediatric liver transplant (PLT) recipients have lower quality-of-life compared to peers. Patient-reported outcome measures (PROMs) are standardised instruments that capture data about patients’ symptoms, functional status, and quality-of-life. Integrating PROMs into routine care enables monitoring of health status and well-being, allowing earlier tailored interventions to improve quality-of-life. Integration of PROMs within PLT services has not been established in Australia.

Aims: Develop recommendations for integrating PROMs within clinical care for PLT recipients at The Royal Children’s Hospital Melbourne.

Methods: A comprehensive literature review and semi-structured interviews with subject matter experts were undertaken to analyse and synthesis implementation key issues.

Results: No literature on PROMs implementation in PLT was identified. Research on integrating PROMs in paediatric care emphasises structured implementation guided by implementation research theories and frameworks. Understanding local barriers and facilitators to implementation and achieving buy-in is key for sustainable integration. Themes with subthemes summarise characterstics impacting implementation: (1) defining the purpose; relating to establishing a shared vision with stakeholders, (2) co-designing and planning; relating to knowledge, attitudes, and beliefs, working environment, intervention availability, and patient-level barriers, and (3) preparing the organisation and clinicians; relating to translating knowledge, electronic-medical record integration, establishing resources, and culture change. Despite PLT validated PROMs, no consensus in tool selection within the PLT international community exists.

Conclusion: Implementation of PROMs in PLT is complex. Implementation strategies and supporting change through co-design are recommended. Assessing and addressing barriers to implementation supports buy-in from stakeholders. Developing consensus in PROM tool selection with liver transplant experts is needed.

SHORT COURSE TOTAL LYMPHOID IRRADIATION (TLI) PRE-HEART TRANSPLANT (HTx) FOR HIGHLY SENSITIZED RECIPIENTS

LEE F 1 , FAZACKERLEY C 1 , KIRUPANANTHER H 2 , VAZ C 2 , TRUONG L 3 , DOWNING J 3 , D’ORSOGNA L 4 , LIM T 5 , SHAH A 1 , LAM K 1

1 Advanced Heart Failure and Transplant Unit, Fiona Stanley Hospital, Perth, 2 Radiation Oncology, Sir Charles Gairdner Hospital, Perth, 3 Pathwest, Fiona Stanley Hospital, Perth, 4 Department of Clinical Immunology, Fiona Stanley Hospital, Perth, 5 Radiation Oncology, Fiona Stanley Hospital, Perth

Aims: A report of two highly sensitised recipients who received short course TLI pre-HTx.

Methods: Information was obtained from electronic medical records and transplant databases.

Results: Case 1 is a 43-year-old female (calculated panel-reactive antibody (cPRA) class I 85%, class II 63%) who required extracorporeal membrane oxygenation (ECMO) support and a left ventricular assist device for proximal LAD dissection and cardiogenic shock. Case 2 is a 50-year-old diabetic female (cPRA class I 90%, class II 0%) with ischaemic heart disease and refractory angina despite multiple surgical and percutaneous revascularization attempts. Pre-transplant desensitization with mycophenolate and rituximab did not alter her immune profile. Both had remote pregnancies and blood transfusions. They received 4.5Gy of TLI (four fractions over four consecutive days) and underwent HTx 92 and 58 days post-TLI respectively. Complement-dependent cytotoxicity T-cell crossmatches were negative however Case 2 had a weakly positive B-cell crossmatch. Both received induction (basiliximab and anti-thymocyte globulin respectively), plasmapheresis and routine maintenance immunosuppression with a persistent reduction in their donor specific antibody profile (Figure 1). Case 2 had primary graft dysfunction requiring temporary ECMO post-HTx. Both patients are alive (more than 5 and 7 years respectively post HTx) with preserved graft function, and no significant lymphophenias or rejection. Case 1 was diagnosed with myelodysplasia five years post-HTx and remains on chemotherapy.

Conclusions: Western Australia is geographically remote with a limited donor pool. Short course TLI is an alternative desensitization strategy pre-HTx however further studies are required to assess the longer-term safety and efficacy of this treatment.

Figure 1: Timeline of Class I and II donor specific antibody MFI trends for Cases 1 and 2. The red and green vertical lines represent time of TLI and HTx respectively.

SIR-ZOSTER: IMMUNOGENICITY OF RECOMBINANT ZOSTER VACCINATION IN KIDNEY TRANSPLANT RECIPIENTS AND HEALTHY COHABITANTS

PERKINS G 1 , PENKO D 1 , TUNBRIDGE M 1 , CHAI CS 2 , HURTADO P 2 , GRUBOR-BAUK B 2 , IRISH G 1 , SHI B 3 , SINGER J 4 , YING T 4 , CHADBAN S 4 , COATES PT 1

1 Central and Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, 2 Adelaide Medical School, University of Adelaide, 3 Kidney Node, Charles Perkins Centre, University of Sydney, 4 Kidney Centre, Royal Prince Alfred Hospital, Sydney

Background: Kidney transplant recipients (KTRs) remain vulnerable to infection, hospitalisation and death from vaccine-preventable infections. A non-live vaccine against varicella zoster virus (VZV; cause of shingles) is now available for KTRs, however the effect of immunosuppression on vaccine immunogenicity is not known.

Methods: This is a prospective, observational trial to be conducted across the Royal Adelaide Hospital (SA) and the Royal Prince Alfred Hospital (NSW). The study will enroll four groups: [1] KTRs receiving tacrolimus (TAC), mycophenolate mofetil (MMF) and prednisolone (PRED) (N=25); [2] KTRs receiving TAC, mechanistic-target-of-rapamycin inhibitor (mTORi) and PRED (N=25); [3] KTRs receiving mTORi, MMF and PRED (N=25); [4] non-immunosuppressed cohabitants (N=25). Participants will receive 2 doses of recombinant zoster vaccine (RZV), 8 weeks apart. VZV-specific T cell and antibody responses will be assessed at 5 time points (baseline, Week 1, Week 8, Week 16, Week 52) by activation-induced marker assay and ELISA, respectively.

Results: The SIR-ZOSTER study is prospectively registered ( NCT06262776 ) and approved by the relevant human research ethics committee. A flow cytometry panel to evaluate absolute frequencies of leukocyte lineages in whole blood has been established and shows concordance with Complete Blood Counts by Coulter counter. Participant recruitment will begin March 1, 2024.

Conclusion: This trial will be the first to evaluate immunogenicity of the recombinant zoster vaccine in KTRs relative to non-immunosuppressed individuals. The influence of 3 common immunosuppression regimens on the formation and longevity of VZV-specific antibody and T cell immunity will be assessed, with data out to 52 weeks. The outcomes will inform subsequent studies of immunosuppression modification to improve vaccine responses in KTRs.

OXYGENATED MACHINE PRESERVATION OF MULTI-VISCERAL BLOCKS FOR TRANSPLANTATION IN A LARGE ANIMAL MODEL

BHATTACHARJYA R , BARNETT D, KANHERE A, DANIEL D, BASTIAN J, BHATTACHARJYA S

Transplant Surgery, University of Adelaide

Aims: This pilot study investigates whether a multi-visceral block can be preserved in an acellular, oxygen-enriched balanced buffered electrolyte solution at ambient temperature less than 39°C.

Methods: A multi-visceral block comprising of the liver, pancreas, small bowel, and kidneys were retrieved from four 80kg Yorkshire pigs with an in-situ flush of cold saline and UW solution. The block was then perfused with an oxygen-enriched, balanced buffered electrolyte solution with albumin at a concentration of 4g/dl and TPN (Baxter TM ) @25ml/kg. 10mg/dL of creatinine was added. The mean PaO 2 achieved was 318mmHg (SD = 119). The block was perfused using a peristaltic pump at a pressure of 30 to 40mmHg. Reperfusion was on a normothermic preservation rig as a surrogate to transplantation with whole blood at 60mmHg.

Results: All blocks demonstrated oxygen consumption accompanied by glucose utilization, ATP production, a physiological response to enteral glucose and renal creatinine clearance. Histological examination and comparison of the blocks from before retrieval to end of preservation and after reperfusion by a blinded senior histopathologist showed no significant change.

Conclusions: The study demonstrates the feasibility of preserving a multi-visceral block with an oxygenated simple buffered electrolyte solution at ambient temperature. The advantage of not being constrained by temperature allows for the creation of simpler, more cost-effective preservation for transplantation.

ROLE OF PHARMACOGENOMICS IN DECEASED DONOR KIDNEY TRANSPLANTATION: A CASE REPORT

PANG J 1 , LIM Z 1 , HO S 1 , TRUONG L 2 , IRISH A 1

1 Department of Nephrology and Renal Transplant, Fiona Stanley Hospital, 2 Department of Clinical Immunology, PathWest, Fiona Stanley Hospital, Western Australia

Introduction: Tacrolimus remains a mainstay component of modern-day immunosuppression in solid organ transplantation, with therapeutic drug monitoring required to prevent acute rejection/toxicity. Genetic variations in cytochrome P450 enzymes (CYP) particularly CYP3A5, have been shown to affect tacrolimus metabolism. Previous studies have highlighted the potential benefits of pharmacogenetic analysis in kidney transplantation, however its clinical application remains limited in Australia.

Case: A 42-year-old Indigenous female with end-stage renal failure secondary to diabetic nephropathy underwent deceased donor kidney transplantation. She received rabbit anti-thymocyte globulin induction due to immunological risk, characterised by HLA 4/6 mismatch and moderate pre-transplant donor-specific antibodies (DSA). Her mPRA was 83.4% with class I (B*40:01 MFI= 1530) and class II (DRB4*01:03 MFI= 2943) DSA. Despite immediate graft function she developed biopsy proven acute antibody-mediated rejection, severe refractory hypertension and TMA ten days post transplantation with rise in class I (B*40:01 MFI= 4287) and II (DRB4*01:03 MFI= 12500) DSA in the setting of refractory low tacrolimus trough levels (<2 ug/mL) despite rapid escalation of tacrolimus dosing. Pharmacogenetic analysis was performed and demonstrated CYP3A5*1/*3 genotype associated with rapid tacrolimus metabolism. CYP3A5*1/*3 genotype was also associated with rapid metabolism of calcium channel blockers which may explain her persistent hypertension despite dose escalation of nifedipine. Unfortunately, the patient had no response to therapy and subsequently underwent graft nephrectomy on day +21.

Conclusion: Our report illustrates the potential clinical utility of pharmacogenomics in deceased donor kidney transplantation. Identifying individuals with actionable genotype can assist in achieving therapeutic drug concentration more rapidly to avoid adverse complications.

TOFACITINIB AS SALVAGE IMMUNOSUPPRESSIVE THERAPY AFTER LUNG TRANSPLANTATION

IVULICH S 1 , KWONG N 1 , SNELL G 2 , PRASAD J 2

1 Department of Pharmacy, Alfred Hospital, Melbourne, 2 Lung Transplant Service, Alfred Hospital, Melbourne

Aims: Conventional immunosuppression regimens after lung transplantation (LTx) are frequently associated with multiple toxicities, limiting immunosuppressive augmentation. Tofacitinib, an oral Janus kinase 3 inhibitor is an alternative immunosuppressant that has shown promise in kidney transplant. However, its use in LTx has not been described.

Methods: We report our experience with this single-center, retrospective case series that included adult LTx recipients treated with tofacitinib-based immunosuppression for cellular mediated rejection. Further escalation of conventional immunosuppression was not feasible in all cases. All patients were at high risk of infection and tofacitinib was selected due to the short half-life, allowing rapid withdrawal in case of severe infection. Antibody mediated rejection or acute infection was excluded prior to initiation.

Results: Seven patients received tofacitinib with a median time to initiation of 715 days [IQR:301-990] post LTx, with median follow up of 84 days [IQR:5-368]. Reasons for initiation included: fibrotic pulmonary infiltrates on chest imaging, oxygen supplementation, minimal improvement with methylprednisolone pulse, declining pulmonary function tests. Serious infection developed in five patients requiring temporary or permanent cessation. Four patients are continuing tofacitinib augmentation with either an improvement or stabilisation of clinical indicators, with spirometry demonstrating restrictive (n=3) or obstructive (n=1) patterns of rejection that were present prior to initiation. Three patients ceased within 10 days of commencement, and all three died from sepsis (n=2) or graft failure (n=1) that could not be linked to tofacitinib.

Conclusion: Tofacitinib appears to be a promising immunosuppressant when introduced as salvage therapy in a select group of LTx recipients.

CHRONIC KIDNEY DISEASE IN NON-KIDNEY SOLID ORGAN TRANSPLANT: A SINGLE CENTRE EXPERIENCE

LIM Z 1 , PANG J 1 , MUSK M 2 , DEMBO L 3 , SWAMINATHAN R 1 , IRISH A 1

1 Department of Nephrology and Renal Transplant, Fiona Stanley Hospital, 2 Advanced Lung Disease Unit, Fiona Stanley Hospital, 3 Advanced Heart Failure and Cardiac Transplantation Unit, Fiona Stanley Hospital, Western Australia

Background: Chronic kidney disease (CKD) is common following non-kidney solid organ transplantation (NK-SOT), with reported prevalence exceeding 25% by 10 years post-transplantation. We seek to review the clinical characteristics and outcomes of NK-SOT patients with CKD.

Methods: Retrospective observational analysis of NK-SOT patients who attended CKD clinic at Fiona Stanley Hospital between 2018 – Sep 2023. Data collected from electronic medical records included baseline demographics, immunosuppression (IS) regimen and biopsy findings. Primary outcome was all-cause mortality or kidney failure, defined as need for long-term renal replacement therapy.

Results: There were 91 patients included, 67.0% were lung and 26.4% cardiac transplant recipients. Median age at transplantation was 56 (IQR 25, 62) years and median duration of post-referral CKD follow-up was 27 (IQR 25, 59) months. Mean eGFR at first CKD outpatient review was 31.4 ± 14.1 ml/min/1.73 m 2 . Primary outcome was observed in 39.6% of patients (death= 26, kidney failure= 18). Most patients remained on a calcineurin inhibitor (CNI)-based IS regimen (87.9%) and triple-agent immunosuppression (63.7%). Only 9 patients underwent kidney biopsy, most with findings showing CNI toxicity and 4 experienced major post-biopsy bleeding. The median time to kidney failure or death was 12.3 years (95% CI = 11.3 – 13.3) post-transplantation (Figure 1). Heart transplant recipients are at a lower adjusted risk of primary event compared to lung transplant recipients (HR 0.24, 95% CI= 0.07 – 0.84, p= 0.025).

Conclusion: CNI toxicity remains as a major cause for CKD in NK-SOT recipients. Prospective studies are required to evaluate the benefits of CNI minimisation in this population group.

A QUALITATIVE CONTENT AND DISCOURSE ANALYSIS COMPARING THE CONSENT SYSTEMS FOR DECEASED ORGAN DONATION IN SPAIN AND ENGLAND

MC LAUGHLIN L 1 , MAYS N 2 , REES K 1 , MILLER C 3 , PAREDES D 4 , NOYES J 1

1 School of Medical and Health Sciences, Bangor University, 2 Policy Innovation and Research Unit, London School of Hygience and Tropical Medicine, 3 Education, NHS Blood and Transplant, 4 University of Barcelona, Hospital Clínic de Barcelona, Spain

Aim: England switched to an opt-out system in 2020 but consent rates to deceased organ donation have not yet improved. Spain also operates a similar opt-out system, yet has almost twice the organ donation rate of the UK. We compared the consent policies and procedures of the two countries to begin to explain this difference.

Methods: Comparative qualitative content and discourse analysis of policy and procedural documents.

Results: There are more pathways to organ donation at end of life in Spain, potentially increasing its visibility and contributing to its normalisation. Families are as involved in decision making in Spain as they are in England, yet the procedural documents used are simpler and reported time taken for consent is much shorter in Spain. The English system focuses on establishing the last known decision of the deceased whereas the Spanish system aims to establish the willingness of the person to donate their organs and more broadly to help others in life. The English approach was more complex and more centralised, with risk-averse protocols, implemented in a health care system with fewer ICU beds and with no legal protections for the potential organ donor’s decision in life (the UK organ donor register has no legal status).

Conclusion: If England’s ambition is to achieve the consent rates consistently seen in Spain, greater legal protection is required to honour the decision of the potential organ donor made in life and there needs to be a shift from impartiality and risk-aversion to promoting organ donation.

SEQUENTIAL KIDNEY TRANSPLANT IN PATIENTS WITH A PREVIOUS LUNG TRANSPLANT; A CASE SERIES

VOGIATZIS L , IRISH A

Nephrology and Renal Transplant, Fiona Stanley Hospital, Perth

Aims: Chronic Kidney disease occurs in approximately 25% of lung transplant recipients leading to end stage renal disease requiring renal replacement therapy. We present sequential renal transplant as a treatment option for these patients, evaluating graft survival, rejection episodes, and infectious and malignant outcomes.

Methods: A single centre observational retrospective study including five lung transplanted patients who underwent renal transplant between 2010-2021. The patients were followed for a minimum duration of 30 months.

Results: All five patients (female 3, male 2) received a kidney transplant within 0-2 years of developing end stage renal disease. Two patients received a deceased donor transplant and three a live donor renal transplant. The average age of patient was 45. Four patients received haemodialysis and one received peritoneal dialysis prior to transplantation. Patients were maintained on their usual lung transplant immunosuppression augmented by increased corticosteroids for four weeks and basiliximab. 3/5 patients developed donor specific antibodies post renal transplant. One patient had persistent donor specific antibodies. None of the patients developed antibody mediated rejection. 2/5 patient’s developed T cell mediated rejection which was successfully treated. The cause of renal failure (atypical haemolytic uraemic syndrome) recurred in one of the patient’s transplant kidney. 2/5 had cytomegalovirus reactivation. Two patients developed skin cancers post transplantation. All had functioning grafts at the end of the follow up period with average creatinine 156 and GFR 47.

Conclusions: Renal transplant is well tolerated and effective post lung transplantation in suitable patients. It requires long-term stringent monitoring and careful patient selection.

PRO-INFLAMMATORY CYTOKINE LEVELS IN BABOON RECIPIENTS OF GENETICALLY MODIFIED PORCINE NEONATAL ISLET CELL CLUSTERS

SALVARIS EJ 1 , FULLER E 2 , LE HT 2 , THOMAS A 2 , HAWTHORNE WJ 3,4 , COWAN PJ 1,5

1 Immunology Research Centre, St Vincent’s Hospital, Melbourne, 2 Centre for Transplant and Renal Research, Westmead Millennium Institute, Westmead Hospital, Sydney, 3 Centre for Transplant and Renal Research, Department of Surgery, Westmead Millennium Institute, Westmead Hospital, 4 Westmead Hospital, School of Medical Sciences, University of Sydney, 5 Department of Medicine, St Vincent’s Hospital, Melbourne

Background: It has been well documented that baboon recipients of pig solid organ xenografts can develop a sustained state of systemic inflammation, evidenced by elevated circulating levels of inflammatory mediators; elevations are also associated with infection and rejection. However, the trajectory of expression of these molecules in pig-to-baboon islet xenotransplantation has not been examined. We prevously reported long-term survival and function of genetically modified porcine neonatal islet cell clusters (NICC) transplanted intraportally into diabetic baboons, with rejection occurring only after elective withdrawal of immunosuppression. In this study, we investigated changes in the inflammatory milieu in these recipients.

Aim: To evaluate serum pro-inflammatory cytokine/chemokine levels in baboon recipients of porcine NICC.

Methods: Pre- and post-transplant sera from recipients (n = 14) were analysed for a range of non-human primate cytokines/chemokines including IL-6, IL-8 and MCP-1, using a Millipore kit.

Results: Notably, IL-6 consistently spiked at 1-6 hours post-transplant (10-350 pg/ml). IL-8 and MCP-1 were rarely elevated early but demonstrated spikes coinciding with post-surgical issues such as wound complications or inflammatory teething episodes. Elevated IL-6 (435 and 2080 pg/ml), IL-8 (1929 and 3045 pg/ml), and MCP-1 (6682 and 13561 pg/ml) levels were detected in two recipients at rejection.

Conclusion: Infusion of porcine NICC resulted in elevated IL-6 levels soon after transplantation, suggesting that peri-transplant treatment with the IL-6 receptor antagonist tocilizumab may be beneficial. However, there was little evidence of sustained systemic inflammation, suggesting efficacy of the immunosuppressive protocol and differences in the response of solid organs compared to islet xenografts.

HUMAN CD4+CD25+CD127LO TREG IN VITRO ACTIVATION WITH ALLOANTIGEN AND RIL-4 INDUCES RECEPTOR FOR INTERLEUKIN 5 (IL-5RΑ)

VERMA ND 1,2 , KAWALIA P 1,2 , AL-ATIYAH R 1,2 , TRAN G 1,2 , RAKESH P 1,2 , CARTER N 1,2 , HODGKINSON SJ 1,2,3 , HALL BM 1,4

1 Immune Tolerance Group, Ingham Institute for Applied Medical Research, 2 South West Sydney Clinical School, University of New South Wales, 3 Department of Neurology, Ingham Institute for Applied Medical Research, 4 Renal Unit, Liverpool Hospital

Aim: Activating human tTreg (CD4 + CD25 + CD127 lo Foxp3 + ) to increase antigen-specific suppression is a therapeutic goal. Rat CD4 + CD25 + Treg activated in vitro with rIL-4/alloantigen (alloAg) express more Foxp3 and CD25, induce IL-5Rα, and are potent suppressors of alloactivation in vitro and in vivo .

Methods: CD4 + CD127 lo CD25 + Treg isolated by FACS from blood of healthy volunteers were cultured for 4 days with rIL-4 (2ng/ml) and irradiated alloAg. Cells were examined, using flow cytometry, for IL-5Rα expression and shifts in Treg subpopulations; resting Pop I (Foxp3 + CD25 + CD45RA + ), activated Pop II (Foxp3 hi CD25 hi CD45RA - ), Treg and activated effector T cell Pop III (Foxp3 + CD25 + CD45RA - ) and chemokine receptors; CXCR3 (Th1), CCR6 (Th17), CCR4 (Th2).

Results: Enriched tTreg had 85.1 ± 9.5% CD4 + CD25 + CD127 lo cells with 14.8 ± 9.9% Pop I, 17.2 ±10.6% Pop II and 48.4 + 8.2% Pop III. <2% cells were Foxp3 + when cultured alone. rIL-4 alone didn’t sustain Pop II (0.27 ± 0.47) and Pop I reduced (7.2 ± 8.7%). Adding rIL-4/alloAg preserved Pop I (25.2 ±15.3) and 1/4 cells in Pop II survived (4.2±1.9%). CCR4 + CXCR3 - CCR6 - (Th2-like cells) increased with rIL-4/alloAg, while % CXCR3 + or CCR6 + cells were similar. IL-5Rα increased in Pop I with alloAg or rIL-4/alloAg. Pop II had more IL-5Rα expressing cells with rIL-4/alloAg (26%) compared to fresh tTreg (0.24%), alloAg (11.8%) or rIL-4 (0%). Pop III with rIL-4 had higher IL-5Rα expression than with rIL-4/alloAg (15.2 vs 4.41%).

Conclusion: Human Treg cultured with alloAg/rIL-4 had induced expression of IL-5Rα and chemokine receptors, consistent with Th2-like Treg. Th2 cytokine IL-4 may promote activation of antigen-specific Treg to improve tolerance inducing therapy.

CHRONIC HEPATITIS E MASQUERADING AS ALLOGRAFT REJECTION IN A LIVER TRANSPLANT RECIPIENT

THORBURN S 1 , SMIBERT O 2

1 Department of Infectious Diseases, Royal Melbourne Hospital, 2 Department of Infectious Diseases and Immunology, Austin Hospital

Introduction: Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. Organ transplant recipients and other immunocompromised hosts are at risk of a chronic form of HEV with rapid progression to cirrhosis. Whilst donor-derived infection can occur, locally transmitted cases in high income countries including Australia are increasingly recognised. In the liver transplant setting, features may be subtle and difficult to distinguish from rejection.

Aims: Review the complexities of hepatitis E epidemiology, diagnosis and management with a focus on the liver transplantation setting.

Methods: Clinical and laboratory features of a case of chronic hepatitis E are described with a review of local epidemiology, diagnostic complexities and management.

Results: A case of chronic hepatitis E following liver transplantation is described in which HEV occurred alongside co-existing rejection, delaying recognition and treatment. Mode of transmission was unable to be identified but did not appear to be donor-derived and occurred shortly following transplantation. Modulation of immunosuppression and adjunctive ribavirin led to resolution of viraemia and hepatitis.

Conclusions: HEV diagnosis in the context of liver transplantation can be elusive. Screening practices prior to organ and blood donation vary worldwide. In addition, testing methodologies have highly variable sensitivities and combinations of serological and molecular methods may be necessary. Management often necessitates a reduction in immunosuppression and may require antiviral therapy. Although seroprevalence rates in Australia approach 6%, HEV remains an underrecognized and underdiagnosed disease with significant consequences for transplant recipients.

Figure 1. Histopathology of liver biopsy samples. 1a) April 2020 biopsy demonstrating mildly increased centrilobular hepatocyte turnover and minimal focal endothelialitis. 1b) January 2023 biopsy demonstrating portal inflammation with a conspicuous nodular infiltrate, lymphocytic cholangitis and foci of endothelialitis. 1c) February 2023 biopsy demonstrating persistence of changes seen in January with developing interface necrosis.

SAFETY AND EFFICACY OF MV140 SUBLINGUAL VACCINE IN PREVENTING RECURRENT URINE INFECTIONS POST RENAL TRANSPLANT: A CASE SERIES

PALLADINO B 1 , O’SHEA-FARREN D 2 , HO S 2 , BOAN P 3 , IRISH A 2 , PEREIRA L 4 , ROBINSON JO 4 , SWAMINATHAN S 2

1 Department of Infectious Diseases, Fiona Stanley Hospital, 2 Department of Nephrology and Transplantation, Fiona Stanley Hospital, 3 Departments of Infectious Diseases and Microbiology, PathWest, Fiona Stanley Hospital, 4 Departments of Infectious Diseases and Microbiology, PathWest, Royal Perth Hospital

AIMS: The primary aim was to determine if the polyvalent MV140 sublingual vaccine (MV140) is safe and tolerated in renal transplant recipients (RTR). The secondary aim was to demonstrate if MV140 is effective in reducing the number or severity of symptomatic urinary tract infections (UTIs) in RTR.

METHODS: Digital medical records of 6 RTR who completed a 3-month course of MV140 were reviewed. Participant age ranged from 38 to 70, 4 were female and 3 had Type 2 Diabetes Mellitus. Average time post-transplant was 4.9 years. Positive urine cultures, microbiology (including colony forming units and urine WBC), symptoms and antibiotic administrations (for treatment and prophylaxis) during the 12 months before and after MV140 were recorded. Medical background, immunosuppression, urethral catheter, ureteric stent, and concurrent prophylaxis measures were recorded.

RESULTS: No adverse reactions or side effects have been reported to date by participants through passive surveillance. There were no episodes of rejection or graft failure during the study period, and mean participant eGFRs were stable (43mL/min/1.73m 2 before MV140, 42mL/min/1.73m 2 after). All patients had decreased UTI and treatment antibiotic days (including IV/SC) post MV140, although there was an increase in prophylactic antibiotic days.

CONCLUSIONS: MV140 was well tolerated in RTR. Some individuals had reduced UTI rate and less antibiotic treatment after MV140 but also had antibiotic prophylaxis which may have affected UTI rate. Further study is required with higher patient numbers, and ideally randomised controlled trial design. Immunological response to vaccine and alternative regimens in RTR might also be explored.

TABLE 1:

Table 1: Absolute number of symptomatic UTIs, UTI-related antibiotic treatment and UTI-related prophylactic antibiotics in the 12 months before and after administration of MV140.

UTILITY OF BARIATRIC SURGERY TO INCREASE ACCESS TO RENAL TRANSPLANTATION: A SINGLE-CENTRE STUDY

TEMLETT J 1 , JAMBOTI J 1 , IRISH A 1 , WARGER A 1 , LIM Z 1 , BALLAL M 2 , SWAMINATHAN R 1 , BHANDARI M 2

1 Department of Nephrology, Fiona Stanley Hospital, Perth, 2 Department of Surgery, Fiona Stanley Hospital, Perth

Renal transplant (RT) is the best treatment for end-stage renal disease (ESRD). Obese patients have limited access to RT and higher mortality and morbidity post-transplant.

Aim: To assess the utility of bariatric surgery (BS) to increase access to RT.

Method : Retrospective review of patients with BMI >30 assessed for RT suitability between 2020-2023.

Results: Over 4 years, 40 patients were referred for BS assessment. Twenty (50%) proceeded to laparoscopic sleeve gastrectomy (LSG) and 12/20 (60%) patients successfully activated on transplant waitlist (TWL). Seven patients proceeded to successful RT. Mean age of those transplanted was 50 years, 5/7were female and 3/7 had diabetic kidney disease. Of the 7 successful RT, mean BMI pre-LSG was 41.6kg/m 2 , mean BMI pre-RT was 28.8kg/m 2 with median weight loss of 33kg per patient at mean duration of 16.5 months. Only 2/7 RT patients had DGF. Surgical complications and graft outcomes are shown in the Table. Nil RT patients developed new-onset diabetes after transplant (NODAT). Mean sustained weight loss post-transplant was -3.3kg (range -5kg to -12kg) at median of 18 months follow-up. Weight gain occurred in 2/7 patients (7kg and 15kg). Two patients (10%) failed to achieve target weight with LSG and continued to Intestinal bypass surgery (SASI) and were not accepted for TWL. Three (15%) LSG patients were placed on hold for TWL, for unrelated medical issues. Only one graft was lost due to post-transplant HUS.

Conclusion: LSG in obese patients with ESRD provides safe and effective weight loss with minimal complications and acceptable post-transplant outcomes.

VIRTUAL CROSSMATCHING: HISTORICAL SAG TESTING MAY NOT ACCURATELY REFLECT CURRENT RECIPIENT ANTIBODY PROFILE AT KIDNEY OFFER

YONG K , LUXTON G, FERNANDO M, STOLER S, KEUNG K

Department of Nephrology, Prince of Wales Hospital, Sydney

We present a 66yo lady on haemodialysis with IgA nephropathy and a failed kidney transplant. She was highly sensitised with calculated panel reactive antibody (cPRA) 84% and multiple class I and II HLA antibodies. She was offered a deceased after circulatory death (DCD) kidney on the 16/11/2023 with 3/6 HLA mismatch and no donor specific antibodies (DSA). This offer was based on single antigen (SAG) testing results of serum dated 08/08/2023. She received anti-thymocyte globulin (ATG) induction (3 doses; 1mg/kg) in addition to standard immunosuppression. She had graft function by day 3 post-transplant. On day 6 (22/11/23), retrospective SAG testing of serum dated 08/11/2023 showed cPRA 99%, positive T- and B-cell flow crossmatch and strong class I and II DSAs to A*24:02 (MFI 6284), A*24:03 (MFI 5752), B*38:02 (MFI 2346) and DRB5*01:01 (MFI 2735). Repeat testing of serum dated 23/11/23 confirmed these results (table 1). Plasmapheresis (PLEX) was commenced, and intravenous immunoglobulin (IVIg) administered. Post-PLEX SAG testing on the 06/12/2023 showed no DSAs. Sequential transplant biopsies showed grade 2A rejection (i 1 t 1 v 1 ) on 30/11/2023 which was treated with pulse IV steroids and persistent borderline rejection (i 1 t 1 v 0 ) on 05/12/2023 which was treated with additional ATG (x3 doses). At 3-months post-transplant, she has good graft function (Cr 137umol/L) with no features of rejection on protocol biopsy. This case highlights a potential flaw in the recently implemented virtual crossmatch system in which historical SAG testing did not accurately reflect the recipient’s current immunological status or antibody profile at the time of kidney offer.

Table 1. Tissue Typing Results Timeline

Is There an Editorial Glass Ceiling? A Gender-Based Cross-Sectional Analysis OF Nephrology and Transplantation Journals

SCARLATO R 1 , WYBURN K 1 , WYLD M 2

1 Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, 2 Department of Renal and Transplant Medicine, Westmead Hospital, Sydney

Aim : Editors in Chief (EiC) play a key role in academic medicine, often shaping research agendas. Women are historically under-represented in EiC roles in medicine. The aim of this study was to examine gender representation amongst EiC in transplantation and nephrology journals.

Methods : A cross sectional analysis of Nephrology and Transplantation journals as listed by Journal Citation Reports (JCR) was performed using binary gender classification (woman or man). The primary outcome was the proportion of women EiC. Secondary outcome was the proportion of women EiC based on journal topic, location and metrics. Descriptive statistics were used. Gender differences were compared using students t-test or Fisher’s exact test.

Results: 73 journals met inclusion criteria. Of these 21 (29%) were transplantation journals, 51(70%) were nephrology journals. Of these, 67 (92%) had single EiC. Of the 79 total EiC, 16 (20%) were women (p<0.001). Transplantation and nephrology journals had 21% and 20% women EiC, respectively (p=0.93) (Figure 1). Journals published in North America had 6 (25%) women, compared to 8 (20%) in Western Europe and no women EiC in Asia -Pacific (p=0.61). There was no statistically significant difference in journal impact factor (p= 0.71) or quartile (p=0.59) by EiC gender.

Conclusions: We found a significant disparity in gender representation in EiC in nephrology and transplantation journals, with men holding 80% of all EiC positions. These findings, amongst growing evidence of underrepresentation of women, highlight a need for targeted efforts to promote gender equity in academic medicine.

Figure 1: Gender proportion of editors in chief by journal type in 2023.

A DECADE OF KIDNEY TRANSPLANT BIOPSY: ADEQUACY, COMPLICATIONS AND DIAGNOSES

HIRSCH D , HONG R, SHANMUGASUNDARAM P

1 Department of Nephrology, St George Hospital, New South Wales

Background: Diagnostic kidney biopsy is essential in the workup of allograft dysfunction. The role of protocol biopsy (in the absence of dysfunction) remains controversial. Here we report the characteristics of transplant biopsies over 10-years.

Methods : We reviewed all transplant biopsies attempted between January 2013 and January 2024 from a single centre. Data was extracted from a transplant database, maintained on site. Missing data was extracted from electronic medical records.

Results : There were 384 transplant biopsies of which 203 (53%) were protocol. Biopsy numbers were expectedly lower in 2020-2022, affected by COVID-19, however the proportion of protocol to indication biopsies was similar between years (range 44-62%). 82% of samples were adequate by BANFF criteria, unaffected by year, and the mean glomeruli sampled per biopsy-core was 12. The most common complications were macroscopic haematuria (3.9%) and symptomatic haematoma (1.6%). Arterio-venous malformation occurred in three patients (0.8%). Compared to indication biopsies, protocol biopsies were more likely to be normal or show only mild/moderate interstitial-fibrosis and tubular-atrophy (61% vs. 30%, p<0.0001). Protocol biopsies had a lower incidence of transplant specific diagnoses (acute-TCMR 2.5% vs. 6.6%, chronic-TCMR 1% vs. 2.2%, acute-ABMR 0% vs. 2.8%, chronic-ABMR 0% vs. 4.4% and BK nephropathy 3% vs. 5.5%). The most common pathological finding was hypertensive change (12% protocol vs. 10% indication).

Conclusions: Over time, the proportion of protocol to indication biopsies was stable. Most protocol biopsies were normal, and less likely to show transplant specific pathology. Above 80% of biopsies were adequate, unaffected by year, and complications were rare.

CHALLENGES AND MANAGEMENT APPROACH TO ENDOVASCULAR ANEURYSM REPAIR AND KIDNEY TRANSPLANTATION: A SYSTEMATIC REVIEW

PEGLER A , SIVAKUMARAN Y

Vascular Surgery, Princess Alexandra Hospital Queensland

Aims. Endovascular aortic aneurysm repair (EVAR) is considered the gold standard in the management of abdominal aortic aneurysms (AAA). The presence of an AAA in a kidney transplant patient or transplant candidate patient, presents a clinical challenge given the risk of complications to either the kidney transplant or endograft respectively. This qualitative systematic review discusses the challenges and management strategies in performing EVAR after kidney transplantation, and kidney transplantation after EVAR, for patients with concurrent AAA and end-stage kidney disease.

Methodology. Previous research relating to kidney transplantation in the setting of EVAR, and EVAR in the setting of kidney transplantation, was sought using databases of published literature, guidelines, and other online material. Studies of any methodological design since 2000 were included and critically appraised for potential bias. Discussions regarding management challenges and feasibility were qualitatively reviewed and collated thematically.

Results. Existing research on this topic is limited to case studies, case series, and small observational studies with no previous reviews of challenges or outcomes in this setting. EVAR after kidney transplantation may lead to arterial access complications and threatened transplant perfusion or nephropathy due to contrast. Comparatively, kidney transplantation after endovascular aneurysm repair may present anastomotic challenges and may precipitate endoleak or endograft complications.

Conclusions. EVAR and kidney transplantation are feasible in combination; however, specific risks should be anticipated depending on the order of treatment.

CLINICAL OUTCOMES OF COVID-19 INFECTION IN SOUTH AUSTRALIAN LUNG TRANSPLANT SATELLITE CENTRE COHORT

BROOKES S , SADLER L, YOUNG M, ANDERSON J, SARKAR P, HOLMES M, HOLMES-LIEW C

SA Lung Transplant Service, Royal Adelaide Hospital

Aim: COVID-19 infection in lung transplant recipients has a high reported mortality due to patient comorbidities and immunosuppression. The South Australian Lung Transplant Unit (SALTU) implemented a pro-active, structured approach to preventing and managing COVID-19 based on international evidence adapted to the local satellite centre setting. This study reviews clinical outcomes of SALTU recipients with COVID-19 to guide future practice.

Methods: Data parameters for acute and longitudinal follow up were determined prior to commencement of this single-centre, observational study. Data from electronic medical records were analysed periodically to inform practice. The SALTU COVID-19 protocol included written information regarding preventive measures, establishment of a dedicated COVID-19 team for clinical management, building continuity, trust and treatment algorithms based on international experience adapted for SA cohort.

Results: 74 LT recipients (60% of cohort) contracted COVID-19 in the analysis period between March 2022 and May 2023. The median age of patients was 55 years and 79% had at least 3 prior COVID-19 vaccinations. 87% were symptomatic at presentation with lethargy and cough most frequently reported. The most common complications were pneumonitis, bacterial pneumonia and acute kidney injury. There were no deaths directly attributable to COVID-19. Pulmonary function tests 6 weeks post-COVID infection showed no significant decline.

Conclusion: This retrospective analysis demonstrates achievement of good clinical outcomes in severely immunocompromised patients can be achieved with targeted, dynamic treatment protocols, best medical therapy and strong adherence from the patient cohort. This model can potentially be applied to similarly high-risk cohorts in future settings.

A RETROSPECTIVE REVIEW: UTILITY OF RADIOLABELLED WHITE CELL SCANS IN DETECTING OCCULT INFECTIONS IN RENAL TRANSPLANT RECIPIENTS

SHEKHAR A 1 , SHEKHAR A 1 , PRESTON J 1 , GRIFFIN A 2

1 Transplant Surgery, Princess Alexandra Hospital, Brisbane, 2 Department of Surgery, Princess Alexandra Hospital, Brisbane

Aims: Infections are a common cause of morbidity and mortality in renal transplant recipients. It is not often where a source cannot be isolated. Pyrexia of unknown origin in this cohort of patients is a diagnostic challenge. In such cases, white cell (WC) labelled scans can be performed to locate an occult septic focus. This retrospective review aims to determine the utility of this investigation to detect occult graft pyelonephritis.

Methods: Retrospective review over a 23-year period (2000-2023) in a single renal transplant institution. Renal transplant recipients who underwent a WC labelled scan to isolate a source of sepsis were included. An in-depth chart review of all cases was performed.

Results: 15 patients over this period had a WC labelled scan to detect a focus of sepsis. 9 (60%) cases reported no source of sepsis, 2 detected bowel infections, 1 detected an abscess in the femoral canal, 1 sacroiliac joint infection, 1 infected cyst in native polycystic kidney and 1 showed diffuse mild uptake in the transplanted kidney. The case with diffuse uptake in the transplanted kidney was not correlated to the clinical picture and was deemed to be physiological uptake in a subsequent radiology meeting.

Conclusions: White cell labelled scans can be beneficial in detecting infections however do not have a specific benefit in detecting occult renal transplant graft pyelonephritis.

GENDER DISPARITIES IN LIVE KIDNEY DONATION- A SINGLE CENTRE RETROSPECTIVE ANALYSIS

LOYALKE A 1 , RANKIN S 2 , PHILLIPS J 1 , SWAMINATHAN R 1

1 Nephrology and Renal Transplant, Fiona Stanley Hospital, 2 South Metropolitan Health service, Fiona Stanley Hospital, Western Australia

Background: Gender disparities in kidney transplantation access have been well described. In Australia and worldwide, women are less likely to be waitlisted for deceased donor transplantation but represent over 60% of live kidney donors.

Aim: To compare patients referred for live kidney donation assessment by gender.

Method : A retrospective review of all patients referred as potential kidney donors at a tertiary centre between 2000-2023. Demographic data and outcomes were collected from electronic medical records, and analysed using RED Cap.

Results : 143/196 patients were referred were included in the analysis. 84/143 (59%) proceeded to kidney donation (female=49; 58%).. Female donors were more often spouse or parent of the recipient. (Table 1). Donor medical ineligibility was the most common reason for not proceeding to donation for both genders but male donors were more likely to be surgically ineligible or lost to follow- up (Table 2).

Conclusion: There are trends attributable to gender in live donation and the reasons for non-progression to kidney donation. Reasons for this need further evaluation.

TABLE 1. RELATIONSHIP OF DONORS TO RECIPIENTS

TABLE 2. REASONS FOR NON-PROGRESSION TO KIDNEY DONATION

RECTUS SHEATH PATCH. A NOVEL SURGICAL TECHNIQUE IN THE REPAIR OF ISOLATED RENAL PELVIS NECROSIS IN A TRANSPLANTED KIDNEY

PRIMROSE S , TAN AL, LAWSON M, RHEE H, GRIFFIN A

Department of Surgery, Princess Alexandra Hospital, Brisbane

Focal necrosis of the renal pelvis in a transplanted kidney is a rare but often morbid complication that may lead to graft loss. Given the scarcity of donor organs, all attempts are made to preserve the graft. Currently there is no standard surgical technique for reconstruction or repair of isolated renal pelvic necrosis. We present the case of a 70-year-old male with end stage kidney disease who underwent renal transplantation. The patient developed a day three post operative urine leak. During surgical exploration a focal area of pelvic necrosis was observed without evidence of proximal or distal ureteric involvement. Given the excellent function of the renal allograft a novel surgical technique was successfully used to repair the necrotic defect. Reconstruction of the renal pelvis was performed using an avascular rectus sheath patch. The patch was secured over the open pelvis following necrotic tissue debridement (Fig 1). The patient made a successful recovery with complete resolution of urine leak. A 6 week post operative retrograde pyelogram confirmed no ongoing urine leak, a baseline creatinine of 131 µmol/L was achieved and the patient discharged from the acute renal transplant unit.

Figure 1. Intraoperative photo showing rectus sheath fascia patched over the pelvic defect, secured with 4.0 PDS interrupted sutures.

EARLY PTLD IN THE NATIVE LUNG OF A SINGLE LUNG TRANSPLANT RECIPIENT: A CASE REPORT

ZHOU W 1 , CASHMAN H 2 , ABBOTT A 1

1 Department of Heart and Lung Transplantation, St Vincents Hospital Sydney, 2 Department of Haematology, St Vincents Hospital Sydney

BACKGROUND: Post Transplant Lymphoproliferative Disorders (PTLD) are serious complications in lung transplant recipients and are frequently Epstein-Barr Virus (EBV) related. 1,2 PTLD occurs more commonly in lung transplant recipients than other solid organ transplants (incidence 2.5-8%). 1,3 The allograft is the primary site of involvement in the majority (71-89%) of cases of PTLD. 3,4 However we report a case of early PTLD occurring in the native lung of a single lung transplant recipient.

CASE REPORT: A 49-year old female received a right single lung transplant for progressive interstitial lung disease with pulmonary hypertension (EBV serostatus D-/R-,CMV serostatus D-/R+).

8-months post-transplant, multiple new intrapulmonary lesions were seen in the native lung, the largest measuring 4.3x4.1x4.3cm. Transthoracic core biopsy demonstrated EBV-positive diffuse large B-cell lymphoma, consistent with monomorphic PTLD. PET scan demonstrated intense uptake in the lung lesions (SUV up to 16.3) with lesions of moderate-intense uptake in the pericardium also identified. No uptake was identified in the transplant lung.

Initial treatment consisted of four doses of weekly rituximab, reduced immunosuppression, and transition from valganciclovir to valaciclovir. Subsequent PET scans following rituximab monotherapy demonstrated a mixed response with improvement in the lung and most pericardial lesions but significant progression in size and intensity of two pericardial lesions. Given the progressive disease on interim PET scan, R-CHOP chemotherapy was commenced aiming for four cycles.

CONCLUSION: We report on the unusual case of native-lung localisation of early PTLD in a lung transplant recipient that demonstrated disease progression despite immunosuppression reduction and rituximab monotherapy, requiring treatment escalation to R-CHOP therapy.

Figure 1. Coronal PET imaging from diagnosis of PTLD in the native lung (left) compared to on completion of four weeks of Rituximab therapy (right), demonstrating improvement in lung lesions but progression in the pericardial lesions.

Figure 2. PET imaging from diagnosis of PTLD in the native lung (left) compared to on completion of four weeks of Rituximab therapy (right), demonstrating improvement in lung lesions but progression in the pericardial lesions.

REFERENCES

1. B. Diane Reams, H. Page McAdams, Howell DN, Steele MP, Davis RD, Palmer SM. Posttransplant Lymphoproliferative Disorder. Chest. 2003 Oct 1;124(4):1242–9.

2. Wudhikarn K, Holman CJ, Linan M, Blaes AH, Dunitz JM, Hertz ME, et al. Post-transplant lymphoproliferative disorders in lung transplant recipients: 20-yr experience at the University of Minnesota. Clinical Transplantation. 2010 Nov 16;25(5):705–13.

3. Bakker NA, Imhoff van, Verschuuren EAM, Son van, van, Nic J G M Veeger, et al. Early onset post‐transplant lymphoproliferative disease is associated with allograft localization. Clinical Transplantation. 2005 Apr 22;19(3):327–34.

4. Kremer BE, Reshef R, Misleh JG, Christie JD, Ahya VN, Blumenthal NP, et al. Post-transplant lymphoproliferative disorder after lung transplantation: A review of 35 cases. The Journal of Heart and Lung Transplantation. 2012 Mar;31(3):296–304.

5. Ghobrial IM, Habermann TM, Macon WR, Ristow KM, Larson TS, Walker RC, et al. Differences between Early and Late Posttransplant Lymphoproliferative Disorders in Solid Organ Transplant Patients: Are They Two Different Diseases? Transplantation. 2005 Jan 27;79(2):244–7.

6. Dharnidharka VR, Green M, Webber SA. Post-Transplant Lymphoproliferative Disorders. Berlin, Heidelberg Springer Berlin Heidelberg; 2010.

TRANSCRIPTOMICS IN BK POLYOMAVIRUS ASSOCIATED NEPHROPATHY: A SCOPING REVIEW

DAVIDSON L 1 , TREVILLIAN P 2 , HEER M 3 , HORVAT J 1 , HIBBERD A 2 , BAINES K 1

1 Immune Health Program, Hunter Medical Research Institute, Newcastle, 2 Hunter Transplant Research Foundation, John Hunter Hospital, Newcastle, 3 Renal Transplant Unit, John Hunter Hospital, Newcastle

Aims: BK polyomavirus (BKPyV) is the most common viral infection experienced by kidney transplant recipients. It reactivates with immunosuppressive therapies and can lead to the development of BKPyV-associated nephropathy (BKPyVAN). The purpose of this scoping review was to assess the use of transcriptomic platforms to profile BKPyVAN in kidney transplant recipients.

Methods: Medline and Embase were searched with the following search strategy: “BK virus” or “BK polyomavirus” or “Polyomavirus” AND “Kidney transplant” or “Nephritis” or “Nephropathy” AND “Gene expression” or “Transcriptomics” or “mRNA”. Papers evaluating the mRNA gene expression profile of BKPyVAN using renal allograft tissue were included.

Results: The search strategy identified 352 publications (248 EMBASE and 104 MEDLINE), and after removal of duplicates (92) and abstract/full-text screening, 11 eligible studies were identified. Of these, 7 were original transcriptomic studies and 4 were bioinformatic studies containing BKPyVAN patients. The gene expression patterns identified in BKPyVAN and T cell mediated rejection have considerable overlap, however viral transcripts may add to highly specific detection of BKPyVAN. The comparison of kidney tissue gene expression in BKPyVAN versus stable transplant recipients unveiled dysregulated expression of innate immune pathways (IL-1β/ inflammasome/ TLRs) and pro-inflammatory pathways (chemokine-, MAPK-, Interferon γ-, T cell- and NFκB-signalling pathways).

Conclusions: This scoping review has demonstrated the potential of transcriptomic profiling in the discovery of novel biomarkers, pathological mechanisms and treatment targets for BKPyVAN. Further studies are needed given the lack of original transcriptomic research that is demonstrated.

BOILING WATER ATP TISSUE EXTRACTION: A NOVEL BENCHMARKING TECHNIQUE FOR ORGAN VIABILITY ASSESSMENT

DANIEL D , BHATTACHARJYA R, BASTIAN J, KANHERE A, BARNETT D, BHATTACHARJYA S

Transplant Surgery, University of Adelaide, South Australia

Aims: To investigate the feasibility of the boiling water ATP extraction method on animal tissue.

Methods: Tissue samples from machine-perfused and static cold-stored porcine livers and kidneys were obtained using an 18-gauge biopsy needle gun. The length of the cores was measured, and the volume was calculated using πdl/4. The samples were snap-frozen using liquid nitrogen and stored at -80°C. Tissue samples were submerged in boiling water after thawing and lysed using an ultrasound homogeniser. The lysed solution was centrifuged for 5 minutes at 12000rpm at 4°C. Bioluminescence was measured using a firefly luciferase solution and a luminometer. ATP Concentration per unit volume was calculated as a mean of 3 assays from a lysed sample.

Results: Stable results and reasonable uncertainty were observed. Isothermic machine-perfused samples decreased after an anoxic period post-retrieval and then increased until the end of preservation whereas SCS samples had decreasing ATP levels throughout preservation, in keeping with physiological hypotheses. SCS samples decreased from a mean

Conclusions: The feasibility of a novel ATP extraction method was displayed in animal tissue. ATP measurement can be done simultaneously with organ preservation and as such may be used for real-time assessment of organ viability.

MANAGING GANCICLOVIR UL97 RESISTANT CYTOMEGALOVIRUS DISEASE AND RECURRENT CELLULAR REJECTION IN A RENAL TRANSPLANT RECIPIENT

CARIJA S 1 , LIM Z 1 , LEE S 2 , HO S 1 , IRISH A 1 , BOAN P 3

1 Department of Nephrology, Fiona Stanley Hospital, 2 Curtin Health Innovation Research Institute, Curtin University, Curtain Medical School, 3 Department of Microbiology, Fiona Stanley Hospital, Western Australia

Introduction: CMV infection after kidney transplant carries significant risk of morbidity and allograft failure.

Case: 21 yo male on haemodialysis for presumed FSGS underwent deceased donor renal transplant; 6/6 mismatch, CMV (D+R-) with standard induction, triple immunosuppression and appropriately dosed prophylactic valganciclovir (450mg daily for creatinine clearance 40-50ml/min). He presented with clinical viral syndrome, graft dysfunction and CMV viremia (6.5 log 10 IU/mL) with ganciclovir UL97 resistance mutation 3 months (3M) post transplant. Transplant biopsy confirmed CMV disease with viral cytopathic change, positive CMV immunohistochemistry in endothelial cells and mononuclear interstitial inflammatory cells. Treatment and CMV viral load is summarised in Figure 1, noting plateau in CMV viral load (~4 log 10 IU/mL) despite initial valganciclovir-based treatment and subsequent high dose letermovir. Repeat biopsy at 6M showed resolution of CMV nephritis but new T cell mediated rejection (TCMR). Viral load reduced to 2 log 10 IU/mL on maribavir for one month (ongoing therapy limited due to cost). Treatment was then maintained with dual valganciclovir and letermovir and later valganciclovir monotherapy. Viral load was undetectable at 17M. QuantiFERON-CMV assay showed no evidence of cell mediated immunity at any timepoint. Due to concurrent refractory TCMR, he received methylprednisolone, ATG and subsequently compassionate mesenchymal stem cell therapy, the latter temporally coinciding with the eventual suppression of CMV viral load. Unfortunately, the case was also complicated by FSGS recurrence and calcineurin inhibitor associated thrombotic microangiopathy.

Conclusion: CMV D+R- transplant with resistant CMV nephritis and refractory TCMR requiring multiple anti-viral combinations.

Figure 1. CMV viral load and associated medication regimen over time.

“ETHICAL DILEMMA IN KIDNEY TRANSPLANT” ARE WE DISADVANTAGING SMOKERS BY EXCLUDING THEM FROM KIDNEY TRANSPLANTATION?

HAZIM H 1 , ROWLANDSON M 1 , CHANG C 1 , POON A 2 , WARD S 1 , HOWLEY P 2 , MACKINNON B 1

1 Department of Nephrology, and Transplantation John Hunter Hospital, Newcastle, 2 Hunter Medical Research Institute, University of Newcastle New South Wales

Background: Studies highlight the detrimental effects of smoking on kidney transplant (KT) outcomes. Most guidelines advocate the cessation of smoking prior to KT. Nevertheless, nicotine addiction is a complex and multifaceted condition.

Methods: We undertook a retrospective observational study of dialysis patients in HNELHD 2013-2023 <65 years old and assessed but not listed for KT. We examined the reasons for non-transplant listing and divided them into two categories, smoking versus others (comorbidities, patient preference, cancer). We compared the categories in terms of demography, comorbidities and dialysis modality. We also conducted a survey of KT units across Australia and NZ regarding their policies toward smoking.

Results: We reviewed the records of 333 patients (142 female), 89 of whom were smokers. Patients not listed due to smoking were less co-morbid than those rejected for another reason (83% vs 40% having ≤1 comorbid condition, p<0.001). Patients rejected due to smoking were younger than those rejected for other reasons (47.8 vs 52.1, p=0.007). There was no difference between the 2 groups in terms of sex or dialysis modality. All the acute kidney transplant units (18) were surveyed (response rate 100%). 72% of units don’t list current smokers for KT.

Conclusion: Patients not listed for KT due to smoking are generally younger and less comorbid than those not listed for other reasons. Our survey shows variation in practice between units. As smoking is more prevalent in marginalised communities not listing these patients for KT may be an equity of access to treatment issue.