Monosodium Urate Crystal Depletion and Bone Erosion Response in Kidney Transplant Recipients With Uncontrolled Gout Treated With Pegloticase: PROTECT Serial Dual-Energy Computed Tomography Findings.

BACKGROUND

Hyperuricemia and gout are associated with poor outcomes in kidney transplant (KT) recipients, including graft failure. The PROspective sTudy of pEglotiCase in Transplant patients (PROTECT) trial showed high urate-lowering efficacy of pegloticase in immunosuppressed KT recipients with uncontrolled gout. Here, we report serial dual-energy computed tomography (DECT) findings in PROTECT participants.

METHODS

KT recipients with uncontrolled gout (serum urate [SU] ≥7 mg/dL, refractory to/intolerant of oral urate-lowering therapy, and symptoms [≥2 flares per year, tophi, and/or gouty arthritis]) and serial DECT imaging were included. Patients were required to have an estimated glomerular filtration rate ≥15 mL/min/1.73 m2 >1 y posttransplant. All patients received pegloticase for ≤24 wk (8 mg infusion every 2 wk) and underwent imaging (screening, week 14, week 24). DECT images were acquired with standard protocols and postprocessed for monosodium urate (MSU) volume (VMSU) using default settings. Regions (bilateral hands/wrists, feet/ankles, knees) with paired screening/week 24 images and screening VMSU ≥0.5 cm3 (minimized DECT-artifact influence) were included.

RESULTS

Eight patients underwent DECT imaging (all men; age: 52.3 ± 11.2 y, time since KT: 18.7 ± 6.9 y, estimated glomerular filtration rate: 45.6 ± 12.4 mL/min/1.73 m2, SU: 10.4 ± 2.1 mg/dL). Six patients (75%) completed the study and received 24 wk of pegloticase therapy, and 2 prematurely discontinued because of COVID-exposure concerns. Of the 6 patients, 4 met imaging inclusion criteria and were included in the analysis. All 4 patients had sustained SU-lowering during month 6 with marked VMSU reduction at week 24 (mean change in VMSU: -98.9%±1.7% [5 imaging regions]). Numerous bone erosions were present in all patients with MSU-adjacent, unknown mineral deposit-adjacent, and deposit-independent erosions. Imaging suggested osteopenia/osteomalacia in 5 patients (83%). After pegloticase treatment, MSU-adjacent erosions decreased in size in a single patient with no DECT evidence of osteopenia/osteomalacia.

CONCLUSIONS

Consistent with prior studies in nontransplant populations, marked depletion of deposited MSU occurred in KT recipients with uncontrolled gout after pegloticase therapy. However, unlike transplant-naive patients, subsequent bone erosion remodeling was not widely observed in urate-adjacent erosions, perhaps due to overall poor bone health in this patient population.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT04087720.