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Na+-K+-2Cl- cotransporter type 2 trafficking and activity: the role of interacting proteins.

The central role of Na+-K+-2Cl- cotransporter type 2 (NKCC2) in vectorial transepithelial salt reabsorption in thick ascending limb cells from Henle's loop in the kidney is evidenced by the effects of loop diuretics, the pharmacological inhibitors of NKCC2, that are amongst the most powerful antihypertensive drugs available to date. Moreover, genetic mutations of the NKCC2 encoding gene resulting in impaired apical targeting and function of NKCC2 transporter give rise to a pathological phenotype known as type I Bartter syndrome, characterised by a severe volume depletion, hypokalaemia and meta

Preventive strategies for acute kidney injury in cancer patients.

Acute kidney injury (AKI) is a common complication of cancer that occurs in up to 50% of neoplastic patients during the natural history of their disease; furthermore, it has a huge impact on key outcomes such as overall prognosis, length of hospitalization and costs. AKI in cancer patients has different causes, either patient-, tumour- or treatment-related. Patient-related risk factors for AKI are the same as in the general population, whereas tumour-related risk factors are represented by compression, obstruction, direct kidney infiltration from the tumour as well by precipitation, aggregatio

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… Prevention of AKI from cast nephropathy has been hypothesized through interference with the binding interaction between free light chains and uromodulin [ 20 ]. … In rats, alkaline urine reduces the interaction of free light chains and uromodulin [ 22 ], but there are no clinical data to support this approach in humans. …

Biomarkers for incident CKD: a new framework for interpreting the literature.

Biomarkers are a useful tool for the investigation of chronic kidney disease (CKD), although the design, analytical tools and outcomes used in many biomarker studies are suboptimal. In part, this situation might reflect a lack of appreciation of the nature of different biomarkers. A particular biomarker could, for example, be implicated in the pathogenesis of CKD because it is a physiological risk factor for declining kidney function, an indicator of impaired kidney function, or a marker of ongoing injury within the kidney. Such risk factors enable us to understand the process of disease and t

Furosemide Stress Test and Biomarkers for the Prediction of AKI Severity.

Clinicians have access to limited tools that predict which patients with early AKI will progress to more severe stages. In early AKI, urine output after a furosemide stress test (FST), which involves intravenous administration of furosemide (1.0 or 1.5 mg/kg), can predict the development of stage 3 AKI. We measured several AKI biomarkers in our previously published cohort of 77 patients with early AKI who received an FST and evaluated the ability of FST urine output and biomarkers to predict the development of stage 3 AKI (n=25 [32.5%]), receipt of RRT (n=11 [14.2%]), or inpatient mortality (n

Oxidized low-density lipoprotein antigen transport induces autoimmunity in the renal tubulointerstitium.

BACKGROUND/AIMS: Chronic kidney disease involves inflammation/oxidative stress, which contributes to progressive kidney injury. METHODS: Male Sprague-Dawley rats underwent 5/6 nephrectomy (Nx) or sham Nx and were sacrificed after 2 days, 2 weeks and 4 weeks. Microarray analysis expression sets over time suggested the evolution of renal lymphocyte infiltration and antigen-presenting cell (APC) activation after 5/6Nx. RT-PCR analysis also confirmed the migration and activation of lymphocytes and APCs through the upregulation of CD3, CXCR3/CXCL10 and CCR7/CCL19 mRNA in remnant kidney (RK). Purif

Prominin-2 is a novel marker of distal tubules and collecting ducts of the human and murine kidney.

Prominin-1 (CD133) and its paralogue, prominin-2, are pentaspan membrane glycoproteins that are strongly expressed in the kidney where they have been originally cloned from. Previously, we have described the localization of prominin-1 in proximal tubules of the nephron. The spatial distribution of prominin-2, however, has not yet been documented in the kidney. We therefore examined the expression of this molecule along distinct tubular segments of the human and murine nephron using in situ hybridization and immunohistochemistry. Our findings indicated that human prominin-2 transcripts and prot

Phenotype and outcome in hereditary tubulointerstitial nephritis secondary to UMOD mutations.

BACKGROUND: UMOD mutations cause familial juvenile hyperuricemic nephropathy (FJHN) and medullary cystic kidney disease (MCKD), although these phenotypes are nonspecific. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We reviewed cases of UMOD mutations diagnosed in the genetic laboratories of Necker Hospital (Paris, France) and of Université Catholique de Louvain (Brussels, Belgium). We also analyzed patients with MCKD/FJHN but no UMOD mutation. To determine thresholds for hyperuricemia and uric-acid excretion fraction (UAEF) according to GFR, these parameters were analyzed in 1097 patients

Почечная трансплантация у пациентов с множественной миеломой: текущие доказательства, вызовы и будущие направления.

Вовлечение реналов является важным осложнением множественной миэломы (ММ) и связано не только с худшими клиническими результатами, но и с более низким качеством жизни, особенно когда речь идет о почечных заболеваниях конечной стадии. Традиционно пациенты ММ не считались имеющими право на трансплантацию почек; однако эти парадигмы меняются. Новая эра лечения MM привела к протеазным ингибиторам, иммуномодулятивным препаратам, моноклональным антителам и, совсем недавно, к клеточной терапии, что привело к более продолжительному выживанию и устойчивой гематологической реакции. Знания цитогенетическ

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… In the loop of Henle and distal tubule, unabsorbed FLCs interact with uromodulin (Tamm–Horsfall protein), forming obstructive casts that induce inflammation and tubular atrophy [ 10 , 11 , 12 ]. … The affinity of FLCs for uromodulin varies, depending on structural determinants within the variable domain, such as the complementarity-determining region 3 (CDR3) of the variable domain of light chains, and partly explains the heterogeneity of LCCN presentation [ 12 , 13 ]. …

High Frequency of Variants of Candidate Genes in Black Africans with Low Renin-Resistant Hypertension.

OBJECTIVES: Black subjects tend to retain salt and water, be more sensitive to aldosterone, and have suppression of plasma renin activity. Variants of the renal sodium channel (ENaC, SCNN1B) account for approximately 6% of resistant hypertension (RHT) in Blacks; other candidate genes may be important. METHODS: Six candidate genes associated with low renin-resistant hypertension were sequenced in Black Africans from clinics in Kenya and South Africa. CYP11B2 was sequenced if the aldosterone level was high (primary aldosteronism phenotype); SCNN1B, NEDD4L, GRK4, UMOD, and NPPA genes were sequen

Mutation of the Na(+)-K(+)-2Cl(-) cotransporter NKCC2 in mice is associated with severe polyuria and a urea-selective concentrating defect without hyperreninemia.

The bumetanide-sensitive Na(+)-K(+)-2Cl(-) cotransporter NKCC2, located in the thick ascending limb of Henle's loop, plays a critical role in the kidney's ability to concentrate urine. In humans, loss-of-function mutations of the solute carrier family 12 member 1 gene (SLC12A1), coding for NKCC2, cause type I Bartter syndrome, which is characterized by prenatal onset of a severe polyuria, salt-wasting tubulopathy, and hyperreninemia. In this study, we describe a novel chemically induced, recessive mutant mouse line termed Slc12a1(I299F) exhibiting late-onset manifestation of type I Bartter syn

Экстракорпоральные стратегии свободного освещения и гемоглозы в эпоху эффективной антимиеломной терапии.

Повреждение реналов затрагивает до половины пациентов с недавно поставленным диагнозом множественной миеломы, и примерно 2-4% из них требуют диализа при презентации, чаще всего из-за нефропатии легкой цепи. У этих пациентов восстановление почек связано со скоростью и величиной сокращения свободных световых цепей (SFLC) в наблюдательных группах - ассоциации, которая в основном отражает гематологическую реакцию на химиотерапию; постепенное преимущество удаления циркулирующих SFLC с помощью экстракорпоральных средств остается неопределенным, и эта повествование построена вокруг этого вопроса в ны

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… In a microperfusion study, Bence–Jones proteins coprecipitated with Tamm–Horsfall glycoprotein (uromodulin) in the lumen of the distal tubule, and light-chain casts are correspondingly identified at or beyond the thick ascending limb of the loop of Henle [ 22 ]. … Because the propensity to bind uromodulin varies markedly among individual light chain clones, two patients with comparable sFLC concentrations may exhibit vastly different renal manifestations. …

Биомаркеры по исследованиям в области клинической медицины: исследование литературы в базе данных PubMed и критическая оценка.

Биомаркер, короткая форма "биологического маркера", появилась в научной литературе в 1940-х годах. С тех пор было предложено множество различных определений, однако общеприменимое объяснение термина " биомаркер " в науке является чрезвычайно сложным. Слово "биомаркер" встречается в 1.3 million статьи в научной базе данных PubMed , которая в настоящее время включает более 39 million Ссылки на биомедицинскую литературу. Биомаркеры тесно связаны со здоровьем и болезнями человека. В настоящей статье делается попытка подойти к многогранному термину "биомаркет" и оценить его с клинической

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… These potential biomarkers include: ➢ Neutrophil gelatinase-associated lipocalin (NGAL); ➢ Galectin-3 and kidney injury molecule-1 (KIM-1); ➢ Interleukin 18 (IL-18); ➢ Immunoglobulin G; ➢ Liver fatty acid-binding protein (L-FABP); ➢ ADMA and SDMA (see above and Table 6 ); ➢ miRNA biomarker, uromodulin … Neutrophil gelatinase-associated lipocalin (NGAL); Galectin-3 and kidney injury molecule-1 (KIM-1); Interleukin 18 (IL-18); Immunoglobulin G; Liver fatty acid-binding protein (L-FABP); ADMA and SDMA (see above and Table 6 ); miRNA biomarker, uromodulin, nephrin, epidermal growth factor (EGF), …

Acute kidney injury in the patient with cancer.

Dramatic advances in the care of patients with cancer have led to significant improvement in outcomes and survival. However, renal manifestations of the underlying cancer as well as the effects of anti-neoplastic therapies leave patients with significant morbidity and chronic kidney disease risks. The most common renal manifestations associated with cancer include acute kidney injury (AKI) in the setting of multiple myeloma, tumor lysis syndrome, post-hematopoietic stem cell therapy, and AKI associated with chemotherapy. Knowledge of specific risk factors, modification of risk and careful atte

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… Light chain cast nephropathy develops when FLCs, which are freely filtered by the glomerulus, bind to Tamm-Horsfall protein (uromodulin) in the thick ascending limb of the loop of Henle to form insoluble casts that obstruct the tubular lumen and lead to local inflammation [ 28 , 29 ]. …

ISN Nexus 2016 Symposia: Translational Immunology in Kidney Disease—The Berlin Roadmap

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… human disease AKI, acute kidney injury; CKD, chronic kidney disease; FSGS, focal segmental glomerulosclerosis; GBM, glomerular basement membrane; GN, glomerulonephritis; IgAN, IgA nephropathy; MPO, myeloperoxidase; NC1, noncollagenous domain 1; THSD7A, thrombospondin type 1 domain-containing 7A; UMOD, uromodulin …

Эффективность и безопасность терапии клеток CAR-T и биконкретных антител в повторной/отредактированной миеломе с повреждением ренальности: анализ пропенсиентности.

Иммунотерапия с перенаправкой Т, включая химериковую антигенную рецепторную терапию T-клеток (CAR-T) и биконкретные антитела (BSAbs), изменила лечение повторной/охлажденной миеломы (RRMMM). В то же время в ходе важнейших регистрационных испытаний, как правило, исключались пациенты с существенными почечными нарушениями (РИ), что создавало критический разрыв в данных о населении, в котором болезни почек 20-50% пациентов с диагнозом. Прямого сопоставления результатов по расчетному спектру широтной фильтрации (eGFR) для обоих вариантов не проводится.МЕТОДЫ: Мы провели ретроспективное когортное исс

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… In the distal tubules, overproduction of monoclonal free light chains leads to cast nephropathy through binding with Tamm–Horsfall protein (uromodulin), causing intrarenal obstruction and tubulointerstitial inflammation. …

Genomic profiling enables personalized strategies to overcome drug resistance in multiple myeloma.

Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of malignant plasma cells within the bone marrow. It is a complex and heterogeneous disease that primarily affects older adults and is associated with significant morbidity and mortality. Despite advances in treatment, including proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, MM remains largely incurable, with most patients experiencing relapse and disease progression. The disease’s biological complexity is driven by a multitude of genetic and molecular alterations, which contr

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… Symptoms include fatigue, confusion, polyuria, and constipation; Renal impairment in MM most commonly results from light-chain cast nephropathy (LCCN), intratubular precipitation of filtered free light chains with uromodulin causing tubular obstruction, and from light-chain deposition disease or AL amyloidosis …

Uncommon Factors Leading to Nephrotic Syndrome.

Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Apart from the traditional causes of NS, such as minimal change disease, focal segmental glomerulosclerosis, diabetes, infections, malignancies, autoimmune conditions, and nephrotoxic agents, there are also rare causes of NS, whose knowledge is of the utmost importance. The aim of this article was to highlight the less well-known causes that have a significant impact on diagnosis and treatment. Genetic syndromes such as Schimke immuno-osseous dysplasia, familial lecithin-cholesterol acyltransfe

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… LC deposition in distal tubules, especially in the presence of Tamm-Horsfall protein (uromodulin), can lead to the formation of cylinders and tubule obstruction, exacerbating interstitial inflammation and fibrosis. …

Biological Role, Mechanism of Action and the Importance of Interleukins in Kidney Diseases.

Each year, the number of patients who are diagnosed with kidney disease too late is increasing, which leads to permanent renal failure. This growing problem affects people of every age, sex and origin, and its full etiopathogenesis is not fully understood, although the involvement of genetic susceptibility, infections, immune disorders or high blood pressure is suggested. Difficulties in making a correct and quick diagnosis are caused by the lack of research on early molecular markers, as well as educational and preventive activities among the public, which leads to the late detection of kidne

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… Kidney-specific DAMPs include Tamm-Horsfall glycoprotein or uromodulin, which are released by tubular damage, while non-specific DAMPs consist of intracellular particles, including histones, a group 1 highly mobile protein (HMGB1), and parts of the cytosol. …

Late Breaking Orals.

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ISEV2021 Abstract Book

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