Nephrology Dialysis Transplantation最新文献

{"title":"Access to kidney transplantation and re-transplantation from childhood to adulthood: long-term data from the ERA Registry.","authors":"Evgenia Preka, Marjolein Bonthuis, Stephen D Marks, Anneke Kramer, Aiko P J de Vries, Søren S Sørensen, Sevcan A Bakkaloğlu, Claus Bistrup, Timo Jahnukainen, Olga L Rodriguez Arévalo, Lukas Buchwinkler, Mårten Segelmark, J Emilio Sanchez, Miha Arnol, Flor A Ordóñez-Álvarez, Francisco de la Cerda-Ojeda, Lucy A Plumb, Shona Methven, Runolfur Palsson, Torbjörn Lundgren, Héctor Ríos, Alberto Ortiz, Vianda S Stel, Jerome Harambat, Kitty J Jager","doi":"10.1093/ndt/gfaf025","DOIUrl":"10.1093/ndt/gfaf025","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>Knowledge regarding access to first kidney transplantation (KT) and subsequent KT in patients commencing kidney replacement therapy (KRT) in childhood is limited.</p><p><strong>Methods: </strong>Using European Renal Association (ERA) Registry data, we investigated European patients who started KRT below 20 years of age between 1978 and 2019. Access and determinants to first, second, and third KT were assessed using multivariable Cox regression.</p><p><strong>Results: </strong>Totals of 12 623, 4077, and 1186 patients were included while awaiting first, second, and third KT, at median ages of 13.8 (IQR: 7.5-17.4), 20.9 (IQR: 16.5-26.1), and 26.6 (IQR: 20.3-32.8) years, respectively. During the study period, overall access was 87.8%, 72.7%, and 60.5% for first, second, and third KT, respectively, and median time to each KT was 0.9 (IQR: 0.2-2.1), 1.9 (0.6-4.5), and 2.6 (IQR: 1.0-5.3) years. Younger age at KRT initiation (aHR 0-4 vs. 10-14 years: 0.54; 95%CI: 0.51-0.57) and female sex (HR: 0.94; 95%CI: 0.90-0.98) were associated with lower access to first KT. KT candidates between 15 and 19 years had lower access to first and second KT (aHR: 0.69; 95%CI: 0.66-0.73, and aHR: 0.70; 95%CI: 0.61-0.81) compared to 10-14 year-olds. Compared to CAKUT, glomerulonephritis patients had lower access to KT (aHR: 0.75; 95%CI: 0.71-0.80 for first, aHR: 0.89; 95%CI: 0.81-0.98 for second, and aHR: 0.80; 95%CI: 0.66-0.97 for third KT). Similarly, patients with primary renal diseases with high risk of recurrence, had lower chances of receiving a first and second KT (aHR: 0.80; 95%CI: 0.76-0.85 for first, aHR: 0.86; 95%CI: 0.78-0.95 for second KT). Access to re-transplantation was also higher with previous pre-emptive KT and previous graft survival exceeding 5 years.</p><p><strong>Conclusion: </strong>Our study highlights KT access disparities particularly for females, the youngest recipients, high-risk age (15-19 years), and diseases with recurrence risk. Notably, pre-emptive transplants and enduring previous grafts offer advantages regarding re-transplantation.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1580-1589"},"PeriodicalIF":5.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12315802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nephrology meets AI-environmental perspective.","authors":"Ivo Laranjinha, Anna Peired, Susi Knoeller, Ana Carina Ferreira, Sonja Gracin, Gulay Demirtas, Maryvonne Hourmant","doi":"10.1093/ndt/gfaf027","DOIUrl":"10.1093/ndt/gfaf027","url":null,"abstract":"","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1449-1451"},"PeriodicalIF":5.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maintaining kidney health in aging societies: a JSN and ERA call to action.","authors":"Alberto Ortiz, Anneke Kramer, Ivan Rychlík, Masaomi Nangaku, Motoko Yanagita, Kitty J Jager, Fergus J Caskey, Vianda S Stel, Naoki Kashihara, Takahiro Kuragano, Yusuke Suzuki, Yoshiaki Takemoto, Hideki Yokoi, Giuseppe Palladino, Danilo Fliser, Roser Torra, Christoph Wanner","doi":"10.1093/ndt/gfaf068","DOIUrl":"10.1093/ndt/gfaf068","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) is the fastest growing cause of death, expected to become the fifth global cause of death and the third in some countries with long life expectancy, such as Japan and Spain, by 2050. This reflects societal aging, as advancing kidney age is the main risk factor for CKD. The forecasted 140% increase in the death rate from CKD by 2050 is reduced to 33% when adjusted for age. The increasing mortality burden is paralleled by higher personal, healthcare, socio-economic and environmental burdens and the need for kidney replacement therapy to treat kidney failure. To some extent, the higher CKD burden represents the price of success in prolonging longevity by decreasing other causes of death. Now is the time to act to minimize the negative impact of CKD on aging societies through primary prevention and early diagnosis and treatment of CKD. Action aimed at maintaining kidney health and delaying biological kidney aging will contribute to healthy aging, as the kidneys have gerosuppressor functions and CKD has the highest negative impact on body aging among chronic non-communicable diseases. This action should be part of a move towards novel holistic approaches to healthy longevity represented by concepts such as cardiovascular-kidney-metabolic health, geromedicine, gerosuppressors and organ rejuvenation. We discuss a conceptual framework for the present and future of kidney aging and kidney health in the elderly, emphasizing opportunities for intervention that underlie the Japanese Society of Nephrology and European Renal Association call to action on Achieving Kidney Health in Aging/Aged Societies.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1498-1511"},"PeriodicalIF":5.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12315803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Red blood cell casts on kidney biopsy and progression of IgA nephropathy.","authors":"Yu-Xuan Yao, Chen Tang, Su-Fang Shi, Pei Chen, Xu-Jie Zhou, Ji-Cheng Lv, Li-Jun Liu, Hong Zhang","doi":"10.1093/ndt/gfaf023","DOIUrl":"10.1093/ndt/gfaf023","url":null,"abstract":"<p><strong>Background: </strong>Renal red blood cell casts (RBCC) are common in IgA nephropathy (IgAN), but their role in kidney disease progression of patients with IgAN remains unclear.</p><p><strong>Methods: </strong>In total, 1425 patients in a Peking University First Hospital IgAN (PKU-IgAN) cohort and 279 patients in the TESTING trial were enrolled to test the association between RBCC and kidney outcome. RBCC was defined as positive (+) when at least one cast was identified within the renal tubules by light microscopy. Kidney endpoint was the composite of the first occurrence of a sustained 30% decrease in estimated glomerular filtration rate or end stage kidney disease or death due to kidney disease. Cox regression analysis was used.</p><p><strong>Results: </strong>In PKU-IgAN, 529 patients (37%) had RBCC; in the TESTING trial, 78 patients (28%) had RBCC. Patients with RBCC had more crescentic lesions, and less segmental sclerosis compared with patients without RBCC. In PKU-IgAN, after a median follow-up of 54 months, 119 patients (22%) with RBCC and 260 patients (29%) without RBCC reached the composite kidney endpoint (P = .009). In multivariable analysis, RBCC was independently associated with composite kidney endpoint [hazard ratios (HR) 0.79; 95% confidence interval (CI) 0.63-0.99; P = .038]. RBCC and immunosuppressive therapy (IST) had an interaction (P = .001). RBCC was independently associated with composite kidney endpoint in patients who received IST (HR 0.56; 95%CI 0.40-0.77; P < .001). In the TESTING trial, after a median follow-up of 57 months, 26 patients (33%) with RBCC, and 96 patients (48%) without RBCC reached the composite kidney endpoint (P = .041). In univariate analysis, RBCC was associated with composite kidney endpoint (HR 0.64; 95%CI 0.42-0.99; P = .047).</p><p><strong>Conclusion: </strong>Renal RBCC was frequent in IgAN and was associated with a higher incidence of acute active lesions and better renal prognosis, especially in those who received IST, warranting particular attention.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1570-1579"},"PeriodicalIF":5.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint (CONFIDENCE) trial: baseline clinical characteristics.","authors":"Rajiv Agarwal, Jennifer B Green, Hiddo J L Heerspink, Johannes F E Mann, Janet B McGill, Amy K Mottl, Julio Rosenstock, Peter Rossing, Muthiah Vaduganathan, Meike Brinker, Robert Edfors, Na Li, Markus F Scheerer, Charlie Scott, Masaomi Nangaku","doi":"10.1093/ndt/gfaf022","DOIUrl":"10.1093/ndt/gfaf022","url":null,"abstract":"<p><strong>Background: </strong>Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitors (SGLT2is) both reduce chronic kidney disease (CKD) progression and improve kidney/cardiovascular (CV) outcomes. The CONFIDENCE (COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint) study (NCT05254002; EudraCT 2021-003037-11) hypothesis is that early combination of finerenone and empagliflozin, an SGLT2i, is superior to either drug alone in reducing urine albumin-to-creatinine ratio (UACR) over 6 months.</p><p><strong>Methods: </strong>CONFIDENCE is an ongoing, fully enrolled, randomized, controlled, double-blind, multicentre phase 2 clinical trial in adults (≥18 years of age) with CKD and type 2 diabetes (T2D), estimated glomerular filtration rate (eGFR) of 30-90 mL/min/1.73 m2 and UACR of ≥100 to <5000 mg/g. Participants taking the clinically maximum tolerated dose of a renin-angiotensin system inhibitor for >1 month at screening were eligible. Participants were randomized 1:1:1 to once-daily finerenone plus empagliflozin, finerenone plus placebo, or empagliflozin plus placebo; doses were 10 mg once daily for empagliflozin and 10 or 20 mg once daily for finerenone, depending on eGFR at baseline. Randomization was stratified by eGFR (<60 or ≥60 mL/min/1.73 m2) and UACR (≤850 or >850 mg/g). The primary efficacy outcome is the relative change in UACR from baseline at Day 180.</p><p><strong>Results: </strong>There were 818 participants randomized across 143 sites from 14 countries between July 2022 and August 2024. Mean (standard deviation) eGFR was 54.2 (17.1) mL/min/1.73 m2. Median (interquartile range) UACR was 583 (292, 1140) mg/g. Mean (standard deviation) HbA1c was 7.3 (1.2)%. Mean systolic/diastolic blood pressure was 135.2/77.3 mmHg. Glucagon-like peptide-1 receptor agonists and insulin were used by 182 (23%) and 313 (39%) participants, respectively. Atherosclerotic CV disease, diabetic retinopathy and a history of heart failure were present in 223 (28%), 126 (16%) and 30 (4%) participants, respectively.</p><p><strong>Conclusions: </strong>The CONFIDENCE trial enrolled a diverse population with CKD and T2D, and will determine the impact of simultaneous initiation of combination finerenone and an SGLT2i versus individual therapy on potentially mitigating the progression of CKD in people with T2D.</p><p><strong>Trial registration number: </strong>ClinicalTrials.gov NCT05254002; EudraCT 2021-003037-11.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1559-1569"},"PeriodicalIF":5.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12315800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated phosphate levels in CKD - a direct threat for the heart.","authors":"Isaac Campos, Christian Faul","doi":"10.1093/ndt/gfaf001","DOIUrl":"10.1093/ndt/gfaf001","url":null,"abstract":"<p><p>Elevations in systemic phosphate levels, also called hyperphosphatemia, occur in chronic kidney disease (CKD) and during the normal aging process, and are associated with various pathologies, such as cardiovascular injury. Experimental studies suggest that at high serum concentrations, phosphate can induce osteogenic differentiation of vascular smooth muscle cells and contribute to vascular calcification. However, the precise underlying mechanism leading to cardiovascular injury is not well understood. Here we discuss how elevations in extracellular phosphate levels could potentially affect cells and intracellular reactions and functions in general. We then zoom in on the heart to discuss whether hyperphosphatemia can have direct pathologic actions beyond inducing vascular calcification. Furthermore, we discuss myocardial calcification as a pathologic event that has not been described and studied in greater detail, but that seems to occur in the context of hyperphosphatemia-induced pathologic cardiac remodeling, as observed in dialysis patients.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1294-1309"},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12207612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DEFENDER trial: dapagliflozin for critically ill patients with acute organ dysfunction-implications for clinicians.","authors":"Jolanta Malyszko, Sophie de Seigneux, Vincenzo Cantaluppi, Stanislas Faguer, Joana Gameiro, Jose Antonio Lopes, Ana B Sanz, Turgay Saritas, Nicholas M Selby, Marlies Ostermann","doi":"10.1093/ndt/gfaf013","DOIUrl":"10.1093/ndt/gfaf013","url":null,"abstract":"","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1267-1269"},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue fibrosis in cardiorenal syndrome: crosstalk between heart and kidneys.","authors":"Abhi Dutta, Sanchari Chakraborty, Antara Roy, Anupam Mittal, Trayambak Basak","doi":"10.1093/ndt/gfaf009","DOIUrl":"10.1093/ndt/gfaf009","url":null,"abstract":"<p><p>Cardiorenal syndrome (CRS) is represented as an intricate dysfunctional interplay between the heart and kidneys, marked by cardiorenal inflammation and fibrosis. Unlike other organs, the repair process in cardiorenal injury involves a regenerative phase characterized by proliferation and polyploidization, followed by a subsequent pathogenic phase of fibrosis. In CRS, acute or chronic cardiorenal injury leads to hyperactive inflammation and fibrotic remodeling, associated with injury-mediated immune cell (macrophages, monocytes and T cells) infiltration and myofibroblast activation. An inflammatory to fibrotic transition corresponds with macrophage transition (M1-M2) associated with increased transforming growth factor (TGF)-β response. Chronic inflammation disrupts hemodynamic pathways, leading to imbalanced oxidative stress and the production of cytokines and growth factors that promote fibrotic stimulation, contributing to pathological cardiorenal remodeling. The inflammatory response paves the pre-fibrotic cardiorenal niche and drives subsequent fibrotic remodeling by activated myofibroblasts. A fibrotic cardiorenal response in CRS is characterized by increased and degradation-resistant deposition of extracellular proteins, especially fibrillar Collagen -I, -III and -V, and non-fibrillar Collagen-IV by active myofibroblasts. Recent advances in basic research animal models of CRS have advanced the knowledge of cardiorenal fibrosis. However, a significant need for clinical applications, trials and evaluation is still needed. Circulating biomarkers like procollagen peptides and TGF-β have clinically been associated with cardiorenal fibrosis diagnosis in CRS. Treatments targeting the fibrotic pathways have also shown efficacy in amelioration of cardiorenal fibrosis in preclinical models. Recent combination therapies targeting multiple fibrotic pathways have been shown to offer promising results. Thus, a understanding of the heterogenic pathological progression and fibrogenesis could identify novel therapeutic approaches for clinical CRS diagnosis and treatment.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1273-1283"},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of the new WHO classification of renal cell carcinoma on the diagnosis of hereditary leiomyomatosis and renal cell carcinoma.","authors":"Jan Degenhardt, Yuri Tolkach, Mahul B Amin, Giovanni Mosiello, Dilek Ertoy Baydar, Emilie Cornec-Le Gall, Jason DiCola, Dean Elhag, Christian Frezza, Jan Halbritter, Ignacio Blanco, Michael A S Jewett, Jean-Baptiste Lattouf, Graham Lovitt, Per-Olof Lundgren, Eamonn R Maher, Peter Mulders, Brian Shuch, Arndt Hartmann, Roman-Ulrich Müller","doi":"10.1093/ndt/gfaf032","DOIUrl":"10.1093/ndt/gfaf032","url":null,"abstract":"<p><p>Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is caused by heterozygous germline variants in the fumarate hydratase (FH) gene. Inheritance follows an autosomal dominant pattern. Loss of FH confers a predisposition for various benign and malignant neoplasms, including cutaneous leiomyomas, uterine fibroids and FH-deficient renal cell carcinoma. While benign, cutaneous and uterine manifestations have a relevant impact on quality of life and risk for complications, the vast majority of FH-deficient RCCs exhibit an aggressive behaviour with invasive growth and the potential for early metastatic spread. Additionally, pathogenic germline FH variants have been associated with other neoplasms, such as adrenal gland and Leydig cell tumours. The aggressive behaviour of FH-deficient RCC challenges nephron-sparing resection strategies, as a wide margin is recommended. Even after early nephrectomy for surgical removal of FH-deficient renal cell carcinomas, there is a relevant risk for distant metastasis as well as the remaining predisposition for de novo primary renal tumours in the other kidney. Active screening is central to HLRCC care since no preventative HLRCC-specific treatment exists. Vascular endothelial growth factor/epidermal growth factor receptor-directed treatment regimes, such as erlotinib/bevacizumab, demonstrate efficacy against HLRCC-associated RCC. This emphasizes the importance of establishing the correct diagnosis in HLRCC early on to guide therapeutic decisions. Morphologic criteria as well as specific immunohistochemical staining and molecular genetics allow the identification of FH-deficient RCC. Changes made in the recent 2022 World Health Organization classification impact the diagnosis of HLRCC in multiple ways. This commentary aims to discuss this impact and raise awareness among pathologists as well as clinicians involved in the care of patients with HLRCC.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1428-1432"},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutralizing the IL-7Rα limits injury in experimental ANCA-associated glomerulonephritis.","authors":"Maliha A Alikhan, Kazuya Kishimoto, Limy Wong, Peemapat Prakongtham, Alana Auden, Kim M O'Sullivan, Juli Jaw, A Richard Kitching","doi":"10.1093/ndt/gfae276","DOIUrl":"10.1093/ndt/gfae276","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>Increased T-cell interkeukin (IL)-7Rα signalling is associated with a poorer prognosis in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. These studies examined the functional role of IL-7Rα (CD127) in experimental glomerulonephritis mediated by anti-myeloperoxidase (MPO) T-cell autoimmunity. We hypothesized that T cells would express IL-7Rα in the kidney and that blocking the function of IL-7Rα, without cellular depletion, would be protective.</p><p><strong>Methods: </strong>Mice were immunized with mouse MPO, then low-dose sheep anti-mouse basement membrane globulin was administered to trigger glomerulonephritis. Flow cytometry and RNA-sequencing characterized intrarenal CD127+-expressing CD4+ and CD8+ T cells in mice with anti-MPO glomerulonephritis. To assess the functional role of IL-7Rα, mice with established anti-MPO autoimmunity were treated with anti-IL-7Rα antibodies.</p><p><strong>Results: </strong>Control ovalbumin-immunized mice given anti-basement membrane globulin developed minimal injury, while MPO-immunized mice given anti-basement membrane globulin developed albuminuria with glomerular and tubulointerstitial injury. Numbers of intrarenal IL-7Rα+ (CD127+) CD4+ and CD8+ T cells were increased in mice with anti-MPO glomerulonephritis. There were 3738 and 2726 genes differentially expressed between intrarenal CD127-PD-1+ and CD127+PD-1- CD8+ and CD4+ T cells, respectively, with substantially overlapping differentially expressed genes between CD8+ and CD4+ T cells. Both CD127-PD-1+ CD8+ and CD4+ T cells were enriched for previously described T-cell exhaustion signatures associated with prognosis in autoimmune disease. As effector memory T cells drive inflammation, we blocked the IL-7Rα after inducing anti-MPO autoimmunity. Anti-IL-7Rα antibodies limited histological injury, and reduced albuminuria numbers of glomerular and interstitial leucocytes, with reduced intrarenal chemokine and pro-inflammatory cytokine expression.</p><p><strong>Conclusions: </strong>Intrarenal effector memory and exhausted CD4+ and CD8+ T cells are present in experimental anti-MPO glomerulonephritis. Neutralizing effector T cells via the IL-7Rα after the induction of autoimmunity limits intrarenal inflammation and disease. IL-7Rα may be a therapeutic target in ANCA-associated vasculitis.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1350-1361"},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}