Pub Date : 2025-11-19DOI: 10.1016/j.xkme.2025.101189
Ayman Al Jurdi , Abraham Cohen Bucay , Pitchaphon Nissaisorakarn , Hannah Gilligan , Claire T. Avillach , Veronica E. Klepeis , Rex N. Smith , Ragnar Palsson , Kassem Safa , Leonardo V. Riella
Immunoglobulin A (IgA) nephropathy is a common cause of kidney failure and can recur after kidney transplantation, increasing the risk of allograft loss. Effective treatments for recurrent IgA nephropathy in kidney transplant recipients are urgently needed. Iptacopan is a complement factor B inhibitor that received accelerated approval by the US Food and Drug Administration in August 2024 for the treatment of high-risk native IgA nephropathy based on trials that excluded transplant recipients. In this case series, we report our early experience with iptacopan in three individuals with biopsy-confirmed recurrent IgA nephropathy after kidney transplant. All received iptacopan for ≥3 months in combination with a short course of systemic corticosteroids. Two individuals demonstrated significant reductions in proteinuria and resolution of microscopic hematuria. One individual developed progressive graft dysfunction; repeat biopsy showed persistent active glomerulonephritis with codeposition of IgG, suggesting a more aggressive or atypical disease phenotype. These early data suggest that iptacopan, in combination with short-term corticosteroids, may offer therapeutic benefit in selected kidney transplant recipients with recurrent IgA nephropathy, warranting further investigation.
{"title":"Early Experience With Iptacopan for Recurrent IgA Nephropathy After Kidney Transplantation","authors":"Ayman Al Jurdi , Abraham Cohen Bucay , Pitchaphon Nissaisorakarn , Hannah Gilligan , Claire T. Avillach , Veronica E. Klepeis , Rex N. Smith , Ragnar Palsson , Kassem Safa , Leonardo V. Riella","doi":"10.1016/j.xkme.2025.101189","DOIUrl":"10.1016/j.xkme.2025.101189","url":null,"abstract":"<div><div>Immunoglobulin A (IgA) nephropathy is a common cause of kidney failure and can recur after kidney transplantation, increasing the risk of allograft loss. Effective treatments for recurrent IgA nephropathy in kidney transplant recipients are urgently needed. Iptacopan is a complement factor B inhibitor that received accelerated approval by the US Food and Drug Administration in August 2024 for the treatment of high-risk native IgA nephropathy based on trials that excluded transplant recipients. In this case series, we report our early experience with iptacopan in three individuals with biopsy-confirmed recurrent IgA nephropathy after kidney transplant. All received iptacopan for ≥3 months in combination with a short course of systemic corticosteroids. Two individuals demonstrated significant reductions in proteinuria and resolution of microscopic hematuria. One individual developed progressive graft dysfunction; repeat biopsy showed persistent active glomerulonephritis with codeposition of IgG, suggesting a more aggressive or atypical disease phenotype. These early data suggest that iptacopan, in combination with short-term corticosteroids, may offer therapeutic benefit in selected kidney transplant recipients with recurrent IgA nephropathy, warranting further investigation.</div></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 2","pages":"Article 101189"},"PeriodicalIF":3.4,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-13DOI: 10.1016/j.xkme.2025.101186
Erin E. Tapper , Johanna M. Huusko , Alicia M. Scocchia , Kimberly Gall , Mary-Beth Roberts , Manuel Bernal-Quirós , Satu Valo , Inka Saarinen , Matias Rantanen , Tuuli Pietila , Massimiliano Gentile , Lotta Koskinen , Meenakshi Mahey Kumar , Samuel Myllykangas , Juha Koskenvuo
<div><h3>Rationale & Objective</h3><div>Mounting evidence supports that identifying the specific molecular etiology for individuals with cystic kidney disease (CyKD) is important for prognostication, surveillance, identifying related living donors, and defining familial risk, even in cases in which a clinical diagnosis appears straightforward. In this study, we aimed to investigate the yield of genetic findings and the unique variant characteristics using multigene panel testing (MGPT) in a referral laboratory setting for an unselected population of patients with an indication of CyKD.</div></div><div><h3>Study Design</h3><div>Cross-sectional study.</div></div><div><h3>Setting & Participants</h3><div>A retrospective analysis of 1,235 genetic testing reports from patients with suspected CyKD who pursued MGPT was performed.</div></div><div><h3>Findings</h3><div>A positive result in a gene associated with CyKD was identified in 49.4% (610/1235) of patient reports, identifying 468 unique variants classified as pathogenic or likely pathogenic in 20 unique genes. Variants in <em>PKD1</em>, a gene complicated by homology to 6 different pseudogenes, contributed to 65.6% (400/610) of positive results. Copy number variants (CNVs) were identified in 9.5% (58/610) of positive results, with 30.4% (17/56) of deletions consisting of 4 exons or less. Variants of uncertain significance that were suspicious for being pathogenic (susVUS) were identified in 57.0% (94/165) of patients with inconclusive results.</div></div><div><h3>Limitations</h3><div>Genetic analysis was targeted to the genes included on the panel at the time of testing. As new evidence emerges supporting additional gene-disease associations, there is potential for additional positive results.</div></div><div><h3>Conclusions</h3><div>Thoughtful selection of carefully curated MGPT optimized to detect technically challenging variants can identify the molecular etiology in individuals presenting with CyKD. Further investigation of susVUS through segregation analysis in families may contribute to additional positive results.</div></div><div><h3>Plain-Language Summary</h3><div>Data informing the yield of multigene panel testing (MGPT) for individuals with cystic kidney disease (CyKD) is increasing. In this study, we retrospectively reviewed MGPT results from 1,235 individuals with suspected CyKD. A positive result in one of 20 CyKD-associated genes, including <em>PKD1</em>, was identified in 49.4% (610/1235) of patient reports. Copy number variants (CNVs) accounted for 9.5% (58/610) of positive results, with 30.4% (17/56) of deletions consisting of 4 exons or less. Suspicious variants of uncertain significance were identified in 57.0% (94/165) of patients with inconclusive results. MGPT can identify the molecular etiology of CyKD and, prior to ordering, should be carefully evaluated for relevant gene content, capabilities for technically challenging genes like <em>PKD1,</em> sensitivity to detect
{"title":"Results of Multigene Panel Testing, Including PKD1, in >1,200 Patients With Cystic Kidney Disease: A Retrospective Analysis","authors":"Erin E. Tapper , Johanna M. Huusko , Alicia M. Scocchia , Kimberly Gall , Mary-Beth Roberts , Manuel Bernal-Quirós , Satu Valo , Inka Saarinen , Matias Rantanen , Tuuli Pietila , Massimiliano Gentile , Lotta Koskinen , Meenakshi Mahey Kumar , Samuel Myllykangas , Juha Koskenvuo","doi":"10.1016/j.xkme.2025.101186","DOIUrl":"10.1016/j.xkme.2025.101186","url":null,"abstract":"<div><h3>Rationale & Objective</h3><div>Mounting evidence supports that identifying the specific molecular etiology for individuals with cystic kidney disease (CyKD) is important for prognostication, surveillance, identifying related living donors, and defining familial risk, even in cases in which a clinical diagnosis appears straightforward. In this study, we aimed to investigate the yield of genetic findings and the unique variant characteristics using multigene panel testing (MGPT) in a referral laboratory setting for an unselected population of patients with an indication of CyKD.</div></div><div><h3>Study Design</h3><div>Cross-sectional study.</div></div><div><h3>Setting & Participants</h3><div>A retrospective analysis of 1,235 genetic testing reports from patients with suspected CyKD who pursued MGPT was performed.</div></div><div><h3>Findings</h3><div>A positive result in a gene associated with CyKD was identified in 49.4% (610/1235) of patient reports, identifying 468 unique variants classified as pathogenic or likely pathogenic in 20 unique genes. Variants in <em>PKD1</em>, a gene complicated by homology to 6 different pseudogenes, contributed to 65.6% (400/610) of positive results. Copy number variants (CNVs) were identified in 9.5% (58/610) of positive results, with 30.4% (17/56) of deletions consisting of 4 exons or less. Variants of uncertain significance that were suspicious for being pathogenic (susVUS) were identified in 57.0% (94/165) of patients with inconclusive results.</div></div><div><h3>Limitations</h3><div>Genetic analysis was targeted to the genes included on the panel at the time of testing. As new evidence emerges supporting additional gene-disease associations, there is potential for additional positive results.</div></div><div><h3>Conclusions</h3><div>Thoughtful selection of carefully curated MGPT optimized to detect technically challenging variants can identify the molecular etiology in individuals presenting with CyKD. Further investigation of susVUS through segregation analysis in families may contribute to additional positive results.</div></div><div><h3>Plain-Language Summary</h3><div>Data informing the yield of multigene panel testing (MGPT) for individuals with cystic kidney disease (CyKD) is increasing. In this study, we retrospectively reviewed MGPT results from 1,235 individuals with suspected CyKD. A positive result in one of 20 CyKD-associated genes, including <em>PKD1</em>, was identified in 49.4% (610/1235) of patient reports. Copy number variants (CNVs) accounted for 9.5% (58/610) of positive results, with 30.4% (17/56) of deletions consisting of 4 exons or less. Suspicious variants of uncertain significance were identified in 57.0% (94/165) of patients with inconclusive results. MGPT can identify the molecular etiology of CyKD and, prior to ordering, should be carefully evaluated for relevant gene content, capabilities for technically challenging genes like <em>PKD1,</em> sensitivity to detect","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 1","pages":"Article 101186"},"PeriodicalIF":3.4,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145787335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-13DOI: 10.1016/j.xkme.2025.101182
Linna Wang, Miaomiao Yang, Lei Yan, Fengmin Shao
<div><h3>Rationale & Objective</h3><div>Idiopathic membranous nephropathy (IMN) is a major cause of nephrotic syndrome. Although rituximab has improved outcomes, resistance or intolerance occurs in a subset of patients. Zuberitamab, a chimeric anti-CD20 immunoglobulin G1 monoclonal antibody, may offer an alternative therapeutic option. This study aimed to evaluate the effectiveness and safety of zuberitamab in patients with phospholipase A2 receptor (PLA2R)–associated IMN.</div></div><div><h3>Study Design</h3><div>Single-center, retrospective observational cohort study.</div></div><div><h3>Setting & Participants</h3><div>Sixty patients with biopsy-proven or serologically diagnosed PLA2R-associated IMN were treated with zuberitamab at Henan Provincial People’s Hospital between July 2023 and June 2024. Thirty-five received zuberitamab as first-line therapy; 25 received it as second-line therapy following prior immunosuppressive treatment.</div></div><div><h3>Intervention(s)</h3><div>Zuberitamab infusions administered in 2-3 doses over several months, guided by B-cell kinetics.</div></div><div><h3>Outcomes</h3><div>The primary outcome was complete or partial remission of proteinuria at 3 and 6 months. Secondary outcomes included changes in serum albumin, serum creatinine, estimated glomerular filtration rate, CD19+ B cells, and anti-PLA2R antibody titers.</div></div><div><h3>Results</h3><div>At month 3, 80% (48/60) of patients achieved remission (5 complete and 43 partial). By month 6, 13 patients achieved complete remission (11 first line and 2 second line; <em>P</em> = 0.03), and 35 achieved partial remission. Serum albumin levels improved, whereas proteinuria and creatinine levels declined in both groups. At 6 months, PLA2R antibody < 2 RU/mL was seen in 90.9% (30/33) of first-line and 81.0% (17/21) of second-line patients (<em>P</em> = 0.29). No serious adverse events were observed.</div></div><div><h3>Limitations</h3><div>Single-center, retrospective design; short follow-up; no direct comparator group; incomplete biomarker data owing to testing limitations.</div></div><div><h3>Conclusions</h3><div>Zuberitamab was associated with favorable clinical and immunologic responses in patients with IMN, including those previously treated with rituximab. These findings support its potential role as a therapeutic option, warranting further validation in prospective studies.</div></div><div><h3>Plain-language Summary</h3><div>Membranous nephropathy is a kidney disease that often causes severe protein loss in the urine. While current treatments like rituximab can be effective, not all patients respond, and some relapse. We studied a newer treatment option called zuberitamab, a type of antibody therapy that also targets immune cells involved in this disease. We looked at 60 patients who received this treatment and tracked how they responded over time. Most patients improved, with many experiencing reduced protein levels and better kidney function.
{"title":"First-line and Second-line Therapy of Zuberitamab in Idiopathic Membranous Nephropathy: A Single-center Retrospective Study","authors":"Linna Wang, Miaomiao Yang, Lei Yan, Fengmin Shao","doi":"10.1016/j.xkme.2025.101182","DOIUrl":"10.1016/j.xkme.2025.101182","url":null,"abstract":"<div><h3>Rationale & Objective</h3><div>Idiopathic membranous nephropathy (IMN) is a major cause of nephrotic syndrome. Although rituximab has improved outcomes, resistance or intolerance occurs in a subset of patients. Zuberitamab, a chimeric anti-CD20 immunoglobulin G1 monoclonal antibody, may offer an alternative therapeutic option. This study aimed to evaluate the effectiveness and safety of zuberitamab in patients with phospholipase A2 receptor (PLA2R)–associated IMN.</div></div><div><h3>Study Design</h3><div>Single-center, retrospective observational cohort study.</div></div><div><h3>Setting & Participants</h3><div>Sixty patients with biopsy-proven or serologically diagnosed PLA2R-associated IMN were treated with zuberitamab at Henan Provincial People’s Hospital between July 2023 and June 2024. Thirty-five received zuberitamab as first-line therapy; 25 received it as second-line therapy following prior immunosuppressive treatment.</div></div><div><h3>Intervention(s)</h3><div>Zuberitamab infusions administered in 2-3 doses over several months, guided by B-cell kinetics.</div></div><div><h3>Outcomes</h3><div>The primary outcome was complete or partial remission of proteinuria at 3 and 6 months. Secondary outcomes included changes in serum albumin, serum creatinine, estimated glomerular filtration rate, CD19+ B cells, and anti-PLA2R antibody titers.</div></div><div><h3>Results</h3><div>At month 3, 80% (48/60) of patients achieved remission (5 complete and 43 partial). By month 6, 13 patients achieved complete remission (11 first line and 2 second line; <em>P</em> = 0.03), and 35 achieved partial remission. Serum albumin levels improved, whereas proteinuria and creatinine levels declined in both groups. At 6 months, PLA2R antibody < 2 RU/mL was seen in 90.9% (30/33) of first-line and 81.0% (17/21) of second-line patients (<em>P</em> = 0.29). No serious adverse events were observed.</div></div><div><h3>Limitations</h3><div>Single-center, retrospective design; short follow-up; no direct comparator group; incomplete biomarker data owing to testing limitations.</div></div><div><h3>Conclusions</h3><div>Zuberitamab was associated with favorable clinical and immunologic responses in patients with IMN, including those previously treated with rituximab. These findings support its potential role as a therapeutic option, warranting further validation in prospective studies.</div></div><div><h3>Plain-language Summary</h3><div>Membranous nephropathy is a kidney disease that often causes severe protein loss in the urine. While current treatments like rituximab can be effective, not all patients respond, and some relapse. We studied a newer treatment option called zuberitamab, a type of antibody therapy that also targets immune cells involved in this disease. We looked at 60 patients who received this treatment and tracked how they responded over time. Most patients improved, with many experiencing reduced protein levels and better kidney function.","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 1","pages":"Article 101182"},"PeriodicalIF":3.4,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145787271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-12DOI: 10.1016/j.xkme.2025.101183
Mineaki Kitamura MD, PhD , Pooya Zardoost DO , Anjali A. Satoskar MD
{"title":"Glomerular Disease in Patients With Acute Kidney Injury After Vancomycin Treatment—Need for Kidney Biopsy","authors":"Mineaki Kitamura MD, PhD , Pooya Zardoost DO , Anjali A. Satoskar MD","doi":"10.1016/j.xkme.2025.101183","DOIUrl":"10.1016/j.xkme.2025.101183","url":null,"abstract":"","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 2","pages":"Article 101183"},"PeriodicalIF":3.4,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-10DOI: 10.1016/j.xkme.2025.101185
Christof Aigner , Zoltán Prohászka , Ágnes Szilágyi , Georg A. Böhmig , Klaus Arbeiter , Alice Schmidt , Gere Sunder-Plassmann
Complement mediated thrombotic microangiopathy (C-TMA) is a rare disease resulting in kidney failure and other organ manifestations. Current treatments include the complement C5 blockers eculizumab and ravulizumab as well as plasma therapy. We report on a young adult man with a long-standing history of genetic C-TMA (GC-TMA) because of a likely pathogenic missense variant in CFH. After several years without clinical signs of TMA and normal kidney function (CKD G1A2), without recent specific therapies, he presented with acute kidney injury, microangiopathic hemolysis, and nephrotic range proteinuria. Plasma therapy and ravulizumab failed to stop hemolysis, and he commenced kidney replacement therapy 11 days after admission. Laboratory analyses disclosed suboptimal complement inhibition and low free ravulizumab serum concentrations. Four weeks after admission, we started treatment with crovalimab, a novel humanized anti-C5 antibody. Hemolysis improved immediately and kidney function recovered after 3 months of dialysis treatment and improved continuously during 1 year of therapy with crovalimab. The excellent and rapid response to crovalimab potentially suggests that the engineering of crovalimab, facilitating also subcutaneous administration, may result in a different pharmacokinetic and pharmacodynamic profile of crovalimab as compared with standard C5 inhibitors in patient with nephrotic range proteinuria.
{"title":"Crovalimab Rescue Therapy in a Case With Genetic Complement Mediated Thrombotic Microangiopathy","authors":"Christof Aigner , Zoltán Prohászka , Ágnes Szilágyi , Georg A. Böhmig , Klaus Arbeiter , Alice Schmidt , Gere Sunder-Plassmann","doi":"10.1016/j.xkme.2025.101185","DOIUrl":"10.1016/j.xkme.2025.101185","url":null,"abstract":"<div><div>Complement mediated thrombotic microangiopathy (C-TMA) is a rare disease resulting in kidney failure and other organ manifestations. Current treatments include the complement C5 blockers eculizumab and ravulizumab as well as plasma therapy. We report on a young adult man with a long-standing history of genetic C-TMA (GC-TMA) because of a likely pathogenic missense variant in <em>CFH</em>. After several years without clinical signs of TMA and normal kidney function (CKD G1A2), without recent specific therapies, he presented with acute kidney injury, microangiopathic hemolysis, and nephrotic range proteinuria. Plasma therapy and ravulizumab failed to stop hemolysis, and he commenced kidney replacement therapy 11 days after admission. Laboratory analyses disclosed suboptimal complement inhibition and low free ravulizumab serum concentrations. Four weeks after admission, we started treatment with crovalimab, a novel humanized anti-C5 antibody. Hemolysis improved immediately and kidney function recovered after 3 months of dialysis treatment and improved continuously during 1 year of therapy with crovalimab. The excellent and rapid response to crovalimab potentially suggests that the engineering of crovalimab, facilitating also subcutaneous administration, may result in a different pharmacokinetic and pharmacodynamic profile of crovalimab as compared with standard C5 inhibitors in patient with nephrotic range proteinuria.</div></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 1","pages":"Article 101185"},"PeriodicalIF":3.4,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145787332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-07DOI: 10.1016/j.xkme.2025.101175
Léa Pessin , Mary K. Roberts , Avrum Gillespie , Catherine R. Butler , Andrea Corradi , Arinala Randrianasolo , Jonathan Daw
<div><h3>Rationale & Objective</h3><div>There are substantial racial/ethnic disparities in access to kidney replacement therapies (KRT). Although existing work often focuses on discrete treatment outcomes, a holistic depiction of racial/ethnic groups’ differential experiences requires a longitudinal approach.</div></div><div><h3>Study Design</h3><div>A sequence analysis in national registry data.</div></div><div><h3>Setting & Participants</h3><div>Adults aged 18-64 years with incident kidney failure in 2009 in the United States Renal Data System database.</div></div><div><h3>Exposure</h3><div>Race/ethnicity (non-Hispanic Asian American [Asian-NH], non-Hispanic African American or Black [Black-NH], Hispanic, and non-Hispanic White [White-NH]) and age group (18-44 years and 45-64 years).</div></div><div><h3>Outcome</h3><div>Ten-year KRT modality sequences (in-center dialysis, home dialysis, deceased donor kidney transplant [DDKT], living donor kidney transplant, stopped dialysis, and mortality).</div></div><div><h3>Analytical Approach</h3><div>Using sequence analysis, longitudinal KRT modalities were characterized using descriptive statistics and visualized with state distribution plots, stratified by race/ethnicity and age.</div></div><div><h3>Results</h3><div>The study included 50,776 adults with kidney failure (24% 18-44 years old and 76% 45-64 years old; 3.6% Asian-NH, 35.8% Black-NH, 17.7% Hispanic, and 42.9% White-NH). Among those aged 18-44, Hispanic and Asian-NH patients more frequently survived 10 years compared with Black-NH and White-NH patients. Among non-White patients, receipt of DDKT increased in years 4-6. Asian-NH patients had the highest DDKT receipt frequency. Asian-NH and White-NH patients more frequently experienced treatment sequences with 3 or more KRT modalities, and these sequences more commonly included transplant. Among patients initially receiving home dialysis, Asian-NH and White-NH patients more commonly transitioned to transplant compared with Black-NH and Hispanic patients. Compared with patients aged 18-44 years, racial/ethnic differences in KRT treatment sequences were attenuated among those aged 45-64 years.</div></div><div><h3>Limitations</h3><div>Descriptive analyses cannot identify causal mechanisms. Excluding patients missing KRT modality may limit generalizability.</div></div><div><h3>Conclusions</h3><div>Patterns in the KRT modality sequences offer a more nuanced view of racial/ethnic disparities in access to treatments for incident kidney failure.</div></div><div><h3>Plain-Language Summary</h3><div>Although much prior research has investigated racial/ethnic differences in kidney failure treatments, they typically focus on one outcome at a time instead of looking at a patient’s full treatment course. This project uses data from the United States Renal Data System to show patterns in patient history in kidney replacement therapies. Patterns in patient history for kidney replacement therapies are shown
{"title":"Kidney Replacement Therapy Sequences: Racial/Ethnic Disparities in End-Stage Kidney Disease Patients’ 10-Year Treatment Histories","authors":"Léa Pessin , Mary K. Roberts , Avrum Gillespie , Catherine R. Butler , Andrea Corradi , Arinala Randrianasolo , Jonathan Daw","doi":"10.1016/j.xkme.2025.101175","DOIUrl":"10.1016/j.xkme.2025.101175","url":null,"abstract":"<div><h3>Rationale & Objective</h3><div>There are substantial racial/ethnic disparities in access to kidney replacement therapies (KRT). Although existing work often focuses on discrete treatment outcomes, a holistic depiction of racial/ethnic groups’ differential experiences requires a longitudinal approach.</div></div><div><h3>Study Design</h3><div>A sequence analysis in national registry data.</div></div><div><h3>Setting & Participants</h3><div>Adults aged 18-64 years with incident kidney failure in 2009 in the United States Renal Data System database.</div></div><div><h3>Exposure</h3><div>Race/ethnicity (non-Hispanic Asian American [Asian-NH], non-Hispanic African American or Black [Black-NH], Hispanic, and non-Hispanic White [White-NH]) and age group (18-44 years and 45-64 years).</div></div><div><h3>Outcome</h3><div>Ten-year KRT modality sequences (in-center dialysis, home dialysis, deceased donor kidney transplant [DDKT], living donor kidney transplant, stopped dialysis, and mortality).</div></div><div><h3>Analytical Approach</h3><div>Using sequence analysis, longitudinal KRT modalities were characterized using descriptive statistics and visualized with state distribution plots, stratified by race/ethnicity and age.</div></div><div><h3>Results</h3><div>The study included 50,776 adults with kidney failure (24% 18-44 years old and 76% 45-64 years old; 3.6% Asian-NH, 35.8% Black-NH, 17.7% Hispanic, and 42.9% White-NH). Among those aged 18-44, Hispanic and Asian-NH patients more frequently survived 10 years compared with Black-NH and White-NH patients. Among non-White patients, receipt of DDKT increased in years 4-6. Asian-NH patients had the highest DDKT receipt frequency. Asian-NH and White-NH patients more frequently experienced treatment sequences with 3 or more KRT modalities, and these sequences more commonly included transplant. Among patients initially receiving home dialysis, Asian-NH and White-NH patients more commonly transitioned to transplant compared with Black-NH and Hispanic patients. Compared with patients aged 18-44 years, racial/ethnic differences in KRT treatment sequences were attenuated among those aged 45-64 years.</div></div><div><h3>Limitations</h3><div>Descriptive analyses cannot identify causal mechanisms. Excluding patients missing KRT modality may limit generalizability.</div></div><div><h3>Conclusions</h3><div>Patterns in the KRT modality sequences offer a more nuanced view of racial/ethnic disparities in access to treatments for incident kidney failure.</div></div><div><h3>Plain-Language Summary</h3><div>Although much prior research has investigated racial/ethnic differences in kidney failure treatments, they typically focus on one outcome at a time instead of looking at a patient’s full treatment course. This project uses data from the United States Renal Data System to show patterns in patient history in kidney replacement therapies. Patterns in patient history for kidney replacement therapies are shown","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 2","pages":"Article 101175"},"PeriodicalIF":3.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-07DOI: 10.1016/j.xkme.2025.101174
Michael P. Toal , Christopher J. Hill , Michael P. Quinn , Emily P. McQuarrie , Charuhas V. Thakar , Ciaran O’Neill , Alexander P. Maxwell
<div><h3>Rationale & Objective</h3><div>There is substantial variation in kidney biopsy practices within and between countries; however, the reasons for this are unclear due to limited research among large diverse populations. The aim of this study was to explore variations in attitude to the indications and contraindications for native kidney biopsy in the United States (US).</div></div><div><h3>Study Design</h3><div>A case-vignette questionnaire was developed. A propensity-to-biopsy score (0-44) was generated from responses to indications and contraindications, with a higher score indicating an increased likelihood to recommend biopsy. Dissemination of the questionnaire occurred by email, social media, and the National Kidney Foundation.</div></div><div><h3>Setting & Participants</h3><div>A total of 295 nephrologists/fellows from 43 states within the US participated.</div></div><div><h3>Exposure</h3><div>All participants completed an identical questionnaire on kidney biopsy practice.</div></div><div><h3>Outcomes</h3><div>Responses were collected on indications, contraindications, and attitudes to biopsy.</div></div><div><h3>Analytical Approach</h3><div>Anonymized IP addresses were collected for comparison between US states. Data were also collected on the demographics of the individual and the type of institution in which the doctor was based.</div></div><div><h3>Results</h3><div>In an adjusted multiple linear regression analysis, higher propensity-to-biopsy scores were demonstrated in US clinicians who were male, younger and more frequent performers of kidney biopsy (<em>P</em> = 0.05). There were significant differences between the 18 US states with 5 or more participants (<em>P</em> < 0.001) with the mean propensity-to-biopsy score ranging from 20.3 (Wisconsin) to 29.2 (New Jersey and Virginia). Increased biopsy propensity was also observed in US states with higher nephrologist density and lower statewide deprivation (<em>P</em> = 0.006).</div></div><div><h3>Limitations</h3><div>The condensed clinical scenarios may not accurately replicate real-world cases, and clinicians opted in often using social media, so generalizability is limited.</div></div><div><h3>Conclusions</h3><div>Attitudes to kidney biopsy practice in the US are highly variable, and clinician or institutional characteristics do not fully explain these discrepancies. Further research is required to understand the factors that influence clinical decision making.</div></div><div><h3>Plain-Language Summary</h3><div>A kidney biopsy can be used to diagnose particular types of kidney disease; however, it exposes patients to a small risk of serious bleeding. A questionnaire was completed by kidney specialist doctors in the United States to determine when this test is best used. There were significant differences in attitudes between these doctors based on their sex, age, and state. States with less poverty and more specialist doctors were shown to have greater willingness t
{"title":"Variation in Attitudes to Native Kidney Biopsy Practice in the United States","authors":"Michael P. Toal , Christopher J. Hill , Michael P. Quinn , Emily P. McQuarrie , Charuhas V. Thakar , Ciaran O’Neill , Alexander P. Maxwell","doi":"10.1016/j.xkme.2025.101174","DOIUrl":"10.1016/j.xkme.2025.101174","url":null,"abstract":"<div><h3>Rationale & Objective</h3><div>There is substantial variation in kidney biopsy practices within and between countries; however, the reasons for this are unclear due to limited research among large diverse populations. The aim of this study was to explore variations in attitude to the indications and contraindications for native kidney biopsy in the United States (US).</div></div><div><h3>Study Design</h3><div>A case-vignette questionnaire was developed. A propensity-to-biopsy score (0-44) was generated from responses to indications and contraindications, with a higher score indicating an increased likelihood to recommend biopsy. Dissemination of the questionnaire occurred by email, social media, and the National Kidney Foundation.</div></div><div><h3>Setting & Participants</h3><div>A total of 295 nephrologists/fellows from 43 states within the US participated.</div></div><div><h3>Exposure</h3><div>All participants completed an identical questionnaire on kidney biopsy practice.</div></div><div><h3>Outcomes</h3><div>Responses were collected on indications, contraindications, and attitudes to biopsy.</div></div><div><h3>Analytical Approach</h3><div>Anonymized IP addresses were collected for comparison between US states. Data were also collected on the demographics of the individual and the type of institution in which the doctor was based.</div></div><div><h3>Results</h3><div>In an adjusted multiple linear regression analysis, higher propensity-to-biopsy scores were demonstrated in US clinicians who were male, younger and more frequent performers of kidney biopsy (<em>P</em> = 0.05). There were significant differences between the 18 US states with 5 or more participants (<em>P</em> < 0.001) with the mean propensity-to-biopsy score ranging from 20.3 (Wisconsin) to 29.2 (New Jersey and Virginia). Increased biopsy propensity was also observed in US states with higher nephrologist density and lower statewide deprivation (<em>P</em> = 0.006).</div></div><div><h3>Limitations</h3><div>The condensed clinical scenarios may not accurately replicate real-world cases, and clinicians opted in often using social media, so generalizability is limited.</div></div><div><h3>Conclusions</h3><div>Attitudes to kidney biopsy practice in the US are highly variable, and clinician or institutional characteristics do not fully explain these discrepancies. Further research is required to understand the factors that influence clinical decision making.</div></div><div><h3>Plain-Language Summary</h3><div>A kidney biopsy can be used to diagnose particular types of kidney disease; however, it exposes patients to a small risk of serious bleeding. A questionnaire was completed by kidney specialist doctors in the United States to determine when this test is best used. There were significant differences in attitudes between these doctors based on their sex, age, and state. States with less poverty and more specialist doctors were shown to have greater willingness t","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 1","pages":"Article 101174"},"PeriodicalIF":3.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145787273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-07DOI: 10.1016/j.xkme.2025.101181
Bartholomeus T. van den Berge , Jitske Jansen , Quinty Leusink , Sanne Kleuskens , Sharon Bootsman , Anne-Els van de Logt , Coralien Vink , Jack FM. Wetzels , Bart Smeets , Rutger J. Maas
<div><h3>Rationale & Objective</h3><div>Clinical outcome of primary nephrotic syndrome (PNS) is highly variable, and predicting an individual patient’s treatment response remains difficult. PNS is characterized by means of podocyte injury and loss. We hypothesized that histologic parameters related to podocyte depletion predict treatment response.</div></div><div><h3>Study Design</h3><div>Retrospective cohort study.</div></div><div><h3>Setting & Participants</h3><div>We analyzed biopsy tissue of 106 patients with PNS (minimal change disease, N = 26; focal segmental glomerulosclerosis, N = 21; and membranous nephropathy [MN], N = 59) and 9 controls. Minimal change disease and focal segmental glomerulosclerosis were considered manifestations of the same entity, defined as idiopathic nephrotic syndrome (iNS), and analyzed as one group. Patients’ baseline clinical and follow-up data were recorded. Kidney biopsies, stained for podocyte-specific and fibrosis markers, were quantitatively analyzed.</div></div><div><h3>Predictors</h3><div>Glomerular density, glomerulosclerosis, podocyte number, podocyte density, and cortical fibrosis.</div></div><div><h3>Outcomes</h3><div>Complete remission (CR) and delayed treatment response.</div></div><div><h3>Analytical Approach</h3><div>Odds ratios and receiver operating characteristic—the area under the curve (ROC-AUC) values identified predictors.</div></div><div><h3>Results</h3><div>In patients with iNS, the respective partial remission and CR rates were 29% and 60% during a median follow-up of 40 months. The majority of patients received high-dose corticosteroid treatment. Quantitation of cortical fibrosis had the highest discriminative power (ROC-AUC value, 0.79; 95% CI, 0.655-0.923) to predict CR. Other significant predictors included podocyte density, nonsclerotic glomerular density, and percentage of nonsclerotic glomeruli.</div><div>In patients with MN, respective partial remission and CR rates were 41% and 54% during a median follow-up of 50 months. The percentage of nonsclerotic glomeruli and nonsclerotic glomerular density were predictors for CR (patients receiving immunosuppressive treatment [ROC-AUC value, 0.71; 95% CI, 0.535-0.893]; patients receiving nonimmunosuppressive treatment alone [ROC-AUC value, 0.80; 95% CI, 0.584-1.000]).</div></div><div><h3>Limitations</h3><div>Relatively small cohorts prevented the use of covariates.</div></div><div><h3>Conclusions</h3><div>In patients with iNS, higher podocyte density and nonsclerotic glomerular density, and lower glomerulosclerosis and cortical fibrosis predicted CR. In patients with MN, lower glomerulosclerosis and higher nonsclerotic glomerular density predicted CR. Biopsy parameters may thus be useful for estimating proteinuria outcome.</div></div><div><h3>Plain-Language Summary</h3><div>Primary nephrotic syndrome (PNS) is characterized by podocyte injury and loss. According to the podocyte depletion hypothesis, the outcome of glomerular injury
{"title":"Biopsy Morphometrics as Predictors of Treatment Response in Primary Nephrotic Syndrome","authors":"Bartholomeus T. van den Berge , Jitske Jansen , Quinty Leusink , Sanne Kleuskens , Sharon Bootsman , Anne-Els van de Logt , Coralien Vink , Jack FM. Wetzels , Bart Smeets , Rutger J. Maas","doi":"10.1016/j.xkme.2025.101181","DOIUrl":"10.1016/j.xkme.2025.101181","url":null,"abstract":"<div><h3>Rationale & Objective</h3><div>Clinical outcome of primary nephrotic syndrome (PNS) is highly variable, and predicting an individual patient’s treatment response remains difficult. PNS is characterized by means of podocyte injury and loss. We hypothesized that histologic parameters related to podocyte depletion predict treatment response.</div></div><div><h3>Study Design</h3><div>Retrospective cohort study.</div></div><div><h3>Setting & Participants</h3><div>We analyzed biopsy tissue of 106 patients with PNS (minimal change disease, N = 26; focal segmental glomerulosclerosis, N = 21; and membranous nephropathy [MN], N = 59) and 9 controls. Minimal change disease and focal segmental glomerulosclerosis were considered manifestations of the same entity, defined as idiopathic nephrotic syndrome (iNS), and analyzed as one group. Patients’ baseline clinical and follow-up data were recorded. Kidney biopsies, stained for podocyte-specific and fibrosis markers, were quantitatively analyzed.</div></div><div><h3>Predictors</h3><div>Glomerular density, glomerulosclerosis, podocyte number, podocyte density, and cortical fibrosis.</div></div><div><h3>Outcomes</h3><div>Complete remission (CR) and delayed treatment response.</div></div><div><h3>Analytical Approach</h3><div>Odds ratios and receiver operating characteristic—the area under the curve (ROC-AUC) values identified predictors.</div></div><div><h3>Results</h3><div>In patients with iNS, the respective partial remission and CR rates were 29% and 60% during a median follow-up of 40 months. The majority of patients received high-dose corticosteroid treatment. Quantitation of cortical fibrosis had the highest discriminative power (ROC-AUC value, 0.79; 95% CI, 0.655-0.923) to predict CR. Other significant predictors included podocyte density, nonsclerotic glomerular density, and percentage of nonsclerotic glomeruli.</div><div>In patients with MN, respective partial remission and CR rates were 41% and 54% during a median follow-up of 50 months. The percentage of nonsclerotic glomeruli and nonsclerotic glomerular density were predictors for CR (patients receiving immunosuppressive treatment [ROC-AUC value, 0.71; 95% CI, 0.535-0.893]; patients receiving nonimmunosuppressive treatment alone [ROC-AUC value, 0.80; 95% CI, 0.584-1.000]).</div></div><div><h3>Limitations</h3><div>Relatively small cohorts prevented the use of covariates.</div></div><div><h3>Conclusions</h3><div>In patients with iNS, higher podocyte density and nonsclerotic glomerular density, and lower glomerulosclerosis and cortical fibrosis predicted CR. In patients with MN, lower glomerulosclerosis and higher nonsclerotic glomerular density predicted CR. Biopsy parameters may thus be useful for estimating proteinuria outcome.</div></div><div><h3>Plain-Language Summary</h3><div>Primary nephrotic syndrome (PNS) is characterized by podocyte injury and loss. According to the podocyte depletion hypothesis, the outcome of glomerular injury","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 1","pages":"Article 101181"},"PeriodicalIF":3.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145787456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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