Clinical journal of the American Society of Nephrology : CJASN最新文献

{"title":"Skeletal Muscle Cramp Prevalence among Patients Receiving Dialysis: A Global Systematic Review and Meta-Analysis.","authors":"Seda Babroudi, Marcelle Tuttle, Eduardo K Lacson","doi":"10.2215/CJN.0000001169","DOIUrl":"10.2215/CJN.0000001169","url":null,"abstract":"<p><strong>Key points: </strong>Multiple point-prevalent studies indicate variable prevalence of skeletal muscle cramps in patients on maintenance dialysis. This is the first focused meta-analysis of the data highlighting how common cramps occur globally and in subset populations by vintage and modality. There is a need for longitudinal and period-prevalent cramp studies to inform how to address skeletal muscle cramps in patients on maintenance dialysis.</p><p><strong>Introduction: </strong>Skeletal muscle cramping among patients with ESKD receiving dialysis is not uncommon and has been identified by patients as a high priority, bothersome, unaddressed physical symptom. The primary objective of this systematic review was to quantify the global prevalence of skeletal muscle cramps among patients on dialysis.</p><p><strong>Methods: </strong>Four databases were searched through September 30th, 2025. All available peer-reviewed observational and nonrandomized experimental studies of nonhospitalized patients receiving dialysis reported in English were included in the analyses, whereas case reports/series, randomized control trials, systematic reviews, and meta-analyses were excluded. Timing of muscle cramps was dichotomized as overall or intradialytic. Random-effects meta-analysis was conducted to quantify the pooled prevalence of skeletal muscle cramps. Risk of bias was assessed using the Newcastle-Ottawa Scale.</p><p><strong>Results: </strong>Ninety-four studies reported the prevalence of muscle cramps in 32,223 patients receiving dialysis across 36 countries on five continents. Most studies were performed in patients on hemodialysis ( n =54, 57%), and 16 studies reported the prevalence of intradialytic cramps specifically. The overall pooled prevalence of skeletal muscle cramps was 55% (95% confidence interval, 50% to 59%; 95% prediction interval 20%-86%), whereas the pooled intradialytic prevalence of skeletal muscle cramps was 33% (95% confidence interval, 22% to 47%; 95% prediction interval, 4%-87%). The prevalence of muscle cramps was higher among patients receiving hemodialysis versus peritoneal dialysis, new/incident versus prevalent patients, and a 4-week versus 1-week survey recall period, with significant between-study heterogeneity. Most studies ( n =50, 53%) were identified as having a moderate risk of bias.</p><p><strong>Conclusions: </strong>The global overall pooled prevalence of muscle cramps among patients receiving dialysis was high (55%), although there were considerable between-study heterogeneity and risk of bias. Our findings highlight the complexity of quantifying skeletal muscle cramps among patients on dialysis and offer insights into specific subpopulations and methods of symptom ascertainment for future epidemiologic, pathophysiologic, and therapeutic studies.</p>","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148671911","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}

{"title":"Pegcetacoplan for Adolescents with C3 Glomerulopathy or Primary Immune Complex Membranoproliferative GN: Phase 3 VALIANT Subgroup Analysis.","authors":"Marina Vivarelli, Gema Ariceta, Yael Borovitz, Bradley P Dixon, Larry A Greenbaum, Christoph Licht, Antonio Mastrangelo, Nabil Melhem, Naoya Fujita, Nicole C A J van de Kar, Dean Wallace, Eli Khankin, Zhongshen Wang, Luis López-Lázaro, Johan Szamosi, Carla M Nester","doi":"10.2215/CJN.0000001077","DOIUrl":"10.2215/CJN.0000001077","url":null,"abstract":"<p><strong>Key points: </strong>Adolescents with C3 glomerulopathy/primary immune complex membranoproliferative GN received pegcetacoplan. Proteinuria reduction and stable eGFR in adolescents were consistent with the overall VALIANT population. Pegcetacoplan may resolve pathophysiology underlying C3 glomerulopathy/primary immune complex membranoproliferative GN and prevent long-term kidney damage in a key patient population.</p><p><strong>Background: </strong>In VALIANT (phase 3; NCT05067127 ), pegcetacoplan (C3/C3b inhibitor) led to significant proteinuria reduction (>68% versus placebo) and eGFR stabilization in native kidney and posttransplant recurrent C3 glomerulopathy and primary immune complex membranoproliferative GN. Here, we describe results for adolescents (12-17 years) in VALIANT.</p><p><strong>Methods: </strong>Patients (randomized 1:1) received pegcetacoplan twice weekly or placebo for 26 weeks. For overall population, the primary end point was baseline-to-week 26 change in log-transformed urine protein-to-creatinine ratio (UPCR) in pegcetacoplan versus placebo arms. Key secondary end points were patients achieving composite renal end point (≤15% eGFR reduction and ≥50% UPCR reduction), patients achieving ≥50% UPCR reduction, and eGFR change.</p><p><strong>Results: </strong>Twenty-eight adolescents received pegcetacoplan; 27 received placebo. Consistent with overall population, pegcetacoplan-treated adolescents achieved clinically meaningful UPCR reduction (relative reduction, 75% [95% confidence interval], 59 to 84; nominal P < 0.001). More adolescents in pegcetacoplan versus placebo arms achieved the composite end point (57% versus 4%; nominal P = 0.002) and ≥50% UPCR reduction (71% versus 4%; nominal P < 0.001). eGFR was stable for pegcetacoplan-treated adolescents (adjusted least squares mean difference [95% confidence interval] versus placebo, +9.7 [-0.026 to 19.382] ml/min per 1.73 m 2 ; nominal P = 0.05). Three adolescents in each group experienced serious treatment-emergent adverse events (pyrexia in one pegcetacoplan-treated patient was considered treatment related). None experienced infection caused by encapsulated bacteria.</p><p><strong>Conclusions: </strong>Pegcetacoplan induced clinically meaningful proteinuria reduction and eGFR stabilization compared with placebo in adolescents with C3 glomerulopathy or primary immune complex membranoproliferative GN and was well tolerated.</p><p><strong>Clinical trial registry name and registration number: </strong>ClincialTrials.gov, NCT05067127 .</p>","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":"1404-1413"},"PeriodicalIF":0.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progression of Cardiovascular-Kidney-Metabolic Syndrome among Hispanic/Latino Adults in the United States: The Hispanic Community Health Study/Study of Latinos.","authors":"Pooja Kondeti, Amit Chakrabarti, Yelena Drexler, Robert A Mesa, Julien O Tremblay, Linda C Gallo, James P Lash, Sylvia E Rosas, Nora Franceschini, Daniele Massera, Claudia Martinez, Martha Daviglus, Matthew Allison, Tali Elfassy","doi":"10.2215/CJN.0000001088","DOIUrl":"10.2215/CJN.0000001088","url":null,"abstract":"<p><strong>Key points: </strong>Eight in ten Hispanic/Latino adults had cardiovascular-kidney-metabolic risk factors or subclinical cardiovascular disease at baseline, with differences by sex and background group. Over 6 years, one in ten regressed to a lower cardiovascular-kidney-metabolic stage while one in five progressed to a higher cardiovascular-kidney-metabolic stage. Higher baseline cardiovascular-kidney-metabolic stage was associated with progressively greater risk of incident cardiovascular disease over 11.4 years.</p><p><strong>Background: </strong>Cardiovascular-kidney-metabolic (CKM) syndrome describes the clustering of risk factors and progression of disease at the intersection of metabolic disorders, CKD, and cardiovascular disease (CVD). The aim of this study was to characterize the prevalence of CKM stages and progression of CKM syndrome among diverse US Hispanic/Latino adults.</p><p><strong>Methods: </strong>The Hispanic Community Health Study/Study of Latinos is a population-based longitudinal cohort of 16,415 Hispanic/Latino adults aged 18-74 years from four US communities. Participants completed examinations at visit 1 (V1, 2008-2011) and visit 2 (2014-2017). Data collected included body mass index, waist circumference, glucose tolerance, lipids, BP, metabolic syndrome, CKD, 10-year CVD risk (to define subclinical CVD), and clinical CVD. CKM stages were defined using American Heart Association criteria: stage 0 (no CKM risk factors), stage 1 (excess/dysfunctional adiposity), stage 2 (metabolic risk factors or CKD), stage 3 (subclinical CVD or risk equivalents), and stage 4 (clinical CVD). We estimated the age-standardized prevalence of CKM stages at V1 ( n =16,123) and CKM stage progression from V1 to visit 2 ( n =11,178). All analyses were weighted and accounted for the Hispanic Community Health Study/Study of Latinos complex survey design.</p><p><strong>Results: </strong>At V1, the mean age was 41.1 years, and 52.3% were female. The distribution of CKM stages was as follows: stage 0, 10.6% (SEM, 0.4); stage 1, 26.1% (SEM, 0.6); stage 2, 50.6% (SEM, 0.6); stage 3, 2.4% (SEM, 0.2); and stage 4, 10.3% (SEM, 0.3). Over an average follow-up of 6 years, 10.3% (SEM, 0.5) regressed to a lower CKM stage, while 21.5% (SEM, 0.7) progressed to a higher CKM stage.</p><p><strong>Conclusions: </strong>Among diverse US Hispanic/Latino adults, eight in ten had CKM risk factors or subclinical CVD and one in five experienced CKM progression over 6 years. These findings highlight the need for targeted, early-stage interventions to prevent CKM progression and improve CKM health in Hispanic/Latino populations.</p>","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":"1326-1339"},"PeriodicalIF":0.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting Risk of Cardiovascular Disease EVENTs Equation for Adverse Cardio-Kidney Outcomes in CKD Population.","authors":"Byounghwi Ko, Chan-Young Jung, Ye Eun Ko, Hee Byung Koh, Cheol Ho Park, Hyung Woo Kim, Jung Tak Park, Seung Hyeok Han, Shin-Wook Kang, Jayoun Kim, Yeong Hoon Kim, Suah Sung, Kyu-Beck Lee, Kook Hwan Oh, Amanda H Anderson, Wei Yang, Jordana B Cohen, Mahboob Rahman, Jong Hyun Jhee, Tae-Hyun Yoo","doi":"10.2215/CJN.0000001078","DOIUrl":"10.2215/CJN.0000001078","url":null,"abstract":"<p><strong>Key points: </strong>The Predicting Risk of Cardiovascular Disease EVENTs score outperformed previous models in prediction of cardio-kidney outcomes. Adding albuminuria to the Predicting Risk of Cardiovascular Disease EVENTs score showed further improvement in patients with CKD. Among East Asian participants, Predicting Risk of Cardiovascular Disease EVENTs provided modest gains in cardiovascular prediction but prominent improvements in predicting kidney outcomes.</p><p><strong>Background: </strong>CKD substantially increases cardiovascular disease (CVD) and mortality risks, yet few models account for integrated cardio-kidney outcomes (CKOs). The American Heart Association's Predicting Risk of CVD EVENTs (PREVENT) score incorporates kidney-specific measures; however, its accuracy for CKOs in patients with CKD remains unclear. We aimed to evaluate PREVENT for CKOs against the pooled cohort equation (PCE) and systematic coronary risk evaluation 2 (SCORE2) in two ethnically distinct CKD cohorts: KoreaN Cohort Study for Outcome in Patients With CKD (KNOW-CKD) from South Korea and Chronic Renal Insufficiency Cohort from the United States.</p><p><strong>Methods: </strong>This study included 4,268 patients with CKD and no known CVD (chronic renal insufficiency cohort: 2,530, KNOW-CKD: 1,738). We compared PREVENT (CVD and atherosclerotic CVD versions) with the PCE and SCORE2. The primary outcome was CKO, a composite of major adverse kidney events (≥50% eGFR decline or kidney failure requiring replacement therapy) and four-point major adverse cardiovascular events (4P-MACEs). Secondary outcomes included individual components and all-cause mortality.</p><p><strong>Results: </strong>The PREVENT-CVD score showed superior predictive accuracy for CKO (Harrell C, 0.688; 95% confidence interval [CI], 0.675 to 0.701) compared with PREVENT-atherosclerotic CVD (delta C [ΔC]=-0.009; 95% CI, -0.011 to -0.007), PCE (ΔC=-0.104; 95% CI, -0.113 to -0.095), and SCORE2 (ΔC=-0.106; 95% CI, -0.114 to -0.097). This superiority was driven by robust prediction for major adverse kidney event, along with significant improvements in reclassification and discrimination for 4P-MACE and all-cause mortality. Although predictive gains for 4P-MACE were attenuated in the KNOW-CKD cohort, adding albuminuria further enhanced predictive performance for primary outcome.</p><p><strong>Conclusions: </strong>The PREVENT-CVD equation outperformed traditional cardiovascular risk models in predicting integrated CKOs in patients with CKD. Its consistent discrimination across both cardiovascular and kidney events suggests that PREVENT may reflect the shared pathophysiology of cardio-kidney disease and support broader risk stratification in CKD.</p><p><strong>Podcast: </strong>This article contains a podcast at https://dts.podtrac.com/redirect.mp3//www.asn-online.org/media/podcast/JASN/2026_07_29_KTS_July2026.mp3.</p>","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":"1310-1325"},"PeriodicalIF":0.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148039000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Far Infrared Radiation on the Proportion of Interventions in Arteriovenous Fistulas in Patients on Hemodialysis: A Randomized Trial.","authors":"Kristine Lindhard, Henrik Post Hansen, Kirstine Gliese, Emilie Hansen, Kristine Hommel, Boye Lagerbon Jensen, Ylian Liem, Brian Lindegaard Pedersen, Mahshid Pourarsalan, Marianne Rix, James Heaf, Ditte Hansen","doi":"10.2215/CJN.0000001079","DOIUrl":"10.2215/CJN.0000001079","url":null,"abstract":"<p><strong>Key points: </strong>Far infrared radiation did not improve the proportion of interventions in arteriovenous fistulas in patients on hemodialysis after 12 months of treatment. No difference was seen between treatment groups in time to intervention, number of thrombosed fistulas, and change in access flow. This study does not support the effect of far infrared radiation on fistula survival as proposed in previous vascular access guidelines.</p><p><strong>Introduction: </strong>In patients on hemodialysis, the risk of arteriovenous fistula (AVF) failure is unacceptably high. Up to 67% of AVFs need an intervention within 1 year after placement. There are no effective treatments to prolong AVF longevity. Far infrared radiation (FIR) treatment has been suggested to enhance AVF survival. The present trial investigated the effect of FIR on the proportion of interventions in the AVF.</p><p><strong>Methods: </strong>In a multicenter, randomized, controlled trial, patients were allocated to receive FIR treatment or no FIR. Eligible patients were patients on chronic hemodialysis with a well-functioning AVF. The FIR group received FIR above the skin of their AVF for 40 minutes at every hemodialysis session for 1 year. The primary outcome was the difference in the proportion of patients with at least one intervention (thrombectomy or percutaneous transluminal angioplasty) after 12 months. The chi-squared test analyzed the difference. Secondary outcomes included differences in the number of thrombosed AVFs, intervention rate, access flow at various time points, and time to first intervention between groups.</p><p><strong>Results: </strong>A total of 115 patients were randomized to the FIR group ( n =58) or the control group ( n =57). Baseline characteristics were similar in both groups. There was no significant difference in the proportion of patients with interventions between the FIR and control groups (19% versus 28%, P = 0.25) or in the proportion with thrombosed AVFs (5% versus 3%, P = 0.26). Time to first intervention was 164 (interquartile range, 86-272) days in the FIR group and 127 (interquartile range, 44-164) days in the control group ( P = 0.26). No differences in the change of access flow occurred ( P = 0.86).</p><p><strong>Conclusion: </strong>During 12 months of treatment, FIR did not affect the overall patency of the AVF. No difference was found in the number of patients with interventions or in any of the secondary endpoints (Clinicaltrials.gov: NCT04011072 ).</p><p><strong>Clinical trial registry name and registration number: </strong>Clinicaltrials.gov: NCT04011072.</p>","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":"1394-1403"},"PeriodicalIF":0.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Twenty Years of CKD Surveillance: From Awareness to Action.","authors":"Scott Reule, Areef Ishani","doi":"10.2215/CJN.0000001157","DOIUrl":"10.2215/CJN.0000001157","url":null,"abstract":"","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":"21 8","pages":"1307-1309"},"PeriodicalIF":0.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148702902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal Hematopoiesis of Indeterminate Potential and Kidney Failure in CKD: An East Asian Cohort Study.","authors":"Minsang Kim, Sanyeowool An, Hyunjin Ryu, Choonghyun Sun, Hong Yul An, Gangpyo Ryu, Jayoun Kim, Yaeni Kim, Soo Wan Kim, Yeong Hoon Kim, Siddhartha Jaiswal, Youngil Koh, Kook-Hwan Oh","doi":"10.2215/CJN.0000001092","DOIUrl":"10.2215/CJN.0000001092","url":null,"abstract":"<p><strong>Key points: </strong>Clonal hematopoiesis of indeterminate potential was more prevalent in patients with CKD than the general population. Clonal hematopoiesis of indeterminate potential was associated with a higher risk of kidney failure in patients with CKD across both the Korean and European ancestry populations. Variant allele fraction of clonal hematopoiesis of indeterminate potential‑associated mutations was higher in patients with CKD than those without CKD.</p><p><strong>Background: </strong>Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition associated with inflammation. Although CKD shares these pathophysiological features, the prognostic role of CHIP on CKD progression remains unclear, particularly in underrepresented East Asian populations.</p><p><strong>Methods: </strong>Deep targeted sequencing of CHIP-driving mutations was used to identify the presence of CHIP, defined as variant allele fraction (VAF) ≥2.0%. CHIP prevalence was compared between 175 Korean participants with CKD in the Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) cohort and 700 matched general population controls in the Gene-Environmental Interaction and Phenotype (GENIE) cohort. The association between CHIP and kidney failure (KF) risk was evaluated using multivariable Cox regression analysis both in the KNOW-CKD cohort and 232 matched UK Biobank participants with CKD. Furthermore, VAF was compared between CHIP-positive participants in the KNOW-CKD and GENIE cohorts.</p><p><strong>Results: </strong>The prevalence of CHIP was significantly higher in the KNOW-CKD cohort than in the GENIE cohort (17% versus 11%; P = 0.04). Over a median follow-up of 10.0 years, 66 participants (38%) developed KF in the KNOW-CKD cohort. After multivariable adjustment, CHIP was associated with higher risk of KF (adjusted hazard ratio, 1.90; 95% confidence interval, 1.03 to 3.51). Furthermore, in the UK Biobank, KF occurred in 43 participants (20%) over a median follow-up of 12.9 years and the association of CHIP with higher risk of KF was consistently observed (adjusted hazard ratio, 2.16; 95% confidence interval, 1.15 to 4.03). Furthermore, among CHIP-positive participants, the median VAF of CHIP-associated mutations was significantly higher in participants within the KNOW-CKD cohort compared with healthy controls in the GENIE cohort (7.3% versus 4.4%; P = 0.02).</p><p><strong>Conclusions: </strong>CHIP is more prevalent in patients with CKD and serves as an independent risk factor of KF. This association is consistently observed across both an underrepresented East Asian cohort and a European cohort, establishing CHIP as a globally relevant risk factor of CKD progression.</p>","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":"1340-1351"},"PeriodicalIF":0.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148230547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Humoral Response to COVID-19 Vaccines and Infection during Sibeprenlimab Treatment of IgA Nephropathy: Data from the ENVISION Trial.","authors":"Kieran McCafferty, Jonathan Barratt, Yusuke Suzuki, Adrian Liew, Dana V Rizk, Bobby Chacko, Laura Kooienga, Richard Lafayette, Muh Geot Wong, Marcela F Pasetti, Mallory C Shriver, Kristin Follman, Courtney Moc Willeford, Manisha Sahay, Gerard Honig, Lee Andrews, Lauren E Olinski, Mohit Mathur, David Oldach","doi":"10.2215/CJN.0000001089","DOIUrl":"10.2215/CJN.0000001089","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Key points: &lt;/strong&gt;The phase 2 ENVISION trial evaluated efficacy and safety of intravenous sibeprenlimab, a selective A PRoliferation-Inducing Ligand inhibitor. Because the trial was conducted during the coronavirus disease 2019 pandemic, we assessed if sibeprenlimab affected humoral responses to coronavirus disease 2019 infection or vaccine. Sibeprenlimab treatment resulted in reduced pathogenic IgA and preserved protective humoral response to coronavirus disease 2019 vaccine and infection.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;In phase 2 ENVISION trial, sibeprenlimab, a selective A PRoliferation-Inducing Ligand inhibitor, significantly decreased proteinuria and stabilized eGFR in adults with IgA nephropathy. This exploratory substudy evaluated coronavirus disease 2019 (COVID-19) severity, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody responses to vaccine and infection, and circulating B-cell populations in patients with IgA nephropathy treated with sibeprenlimab or placebo.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Participants enrolled in ENVISION ( NCT04287985 ) received 12 monthly intravenous infusions of sibeprenlimab (2, 4, or 8 mg/kg) or placebo. COVID-19 infection and vaccination data were recorded for all participants. In a substudy, serum IgG responses to SARS-CoV-2 spike protein, its receptor binding domain (RBD), and nucleocapsid antigen were assessed, with further analysis of serum IgM and IgA and salivary IgA against RBD in a subset of participants. Circulating T cells and B-cell subsets were analyzed by flow cytometry.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Overall, symptomatic COVID-19 incidence was comparable between groups (33.3% sibeprenlimab versus 44.7% placebo), indicating no observable excess risk of COVID-19 infection with sibeprenlimab. Of 155 participants, 72 (sibeprenlimab n =52; placebo n =20) consented to the substudy. Within the substudy, COVID-19 seroconversion rates were 100% for IgG against SARS-CoV-2 RBD (IgG-RBD) after vaccination or infection. Peak IgG-RBD titers after mRNA vaccination exceeded protective thresholds in all COVID-19-naive sibeprenlimab recipients, and IgG-RBD durability was comparable between sibeprenlimab and placebo. COVID-19-specific IgG, IgA, and IgM antibody responses to infection were preserved, and IgA-RBD responses detected in saliva suggested preservation of mucosal immunity with sibeprenlimab. No meaningful perturbations in B or T cells were observed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;A PRoliferation-Inducing Ligand inhibition with sibeprenlimab reduced pathogenic IgA while preserving mucosal immunity and systemic antibody responses to COVID-19 vaccination and infection. The absence of B-cell perturbations and the apparent absence of an increased risk of impaired vaccine response suggest that sibeprenlimab may not confer clinically significant immunosuppressive risks; the substudy's size and exploratory design preclude definitive conclusions, warranting fur","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":"1365-1375"},"PeriodicalIF":0.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148230544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SGLT2 Inhibitors versus GLP-1 Receptor Agonists in Type 2 Diabetes, The Kidney Conundrum.","authors":"Joel Shah","doi":"10.2215/CJN.0000001068","DOIUrl":"10.2215/CJN.0000001068","url":null,"abstract":"","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":"1488"},"PeriodicalIF":0.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147794675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Performance and Resource Utilization of Combining Blood Gene Expression, Cell-Free DNA, and Urine Chemokines for Monitoring Kidney Rejection.","authors":"Akhil Singla, Sook Park, Havisha Pedamallu, Kenny Chen, Blade Robelly, Christabel Rebello, Connor Lantz, Lihui Zhao, Ronnie LaCombe, Rohita Sinha, Genevieve Hanna, Steve Kleiboeker, Sanjay Mehrotra, John Friedewald","doi":"10.2215/CJN.0000001075","DOIUrl":"10.2215/CJN.0000001075","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Key points: &lt;/strong&gt;Two-stage urine chemokine screening improved discrimination and positive predictive value versus blood-only testing while preserving high negative predictive value. In validation, urine chemokine C-X-C motif ligand 9/creatinine screening referred only 79% of samples for donor-derived cell-free DNA testing, reducing blood test use. Standalone blood biomarkers were more consistent for antibody-mediated rejection than cellular rejection; urine chemokine screening improved diagnostic yield.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;After kidney transplantation, subclinical acute rejection occurs in 20%-25% of clinically stable recipients; surveillance biopsies are invasive and often indicate no rejection. Moreover, the widespread use of noninvasive biomarkers is limited by cost.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We developed and sought to validate two-stage diagnostic models integrating urine chemokine assays (chemokine C-X-C motif ligand 9 [CXCL9] and C-X-C motif ligand 10) with confirmatory blood-based gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA). Data from two studies, 476 biopsy-paired samples from 226 recipients (discovery) and 144 samples from 134 recipients (validation), were analyzed retrospectively. Rapid, low-cost urine chemokine assays were used for stage 1 screening; recipients with elevated urine chemokines underwent additional stage 2 testing with GEP and/or dd-cfDNA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In the validation cohort, dd-cfDNA outperformed GEP for overall rejection and antibody-mediated rejection, whereas neither test validated significant discrimination for cellular rejection. CXCL9-based two-stage testing improved the area under the receiver operating characteristic curve and positive predictive value versus standalone stage-2 testing, while maintaining similar negative predictive value and reducing stage 2 test use. At a probability screening threshold of 0.10, the CXCL9/creatinine-based logistic regression, adjusted for BK virus, urinary tract infection, sex, age, time post-transplant, and donor type, followed by dd-cfDNA validated a higher positive predictive value (0.39 versus 0.34), lower sensitivity (0.56 versus 0.62), and similar negative predictive value around 0.94, compared with dd-cfDNA alone, while recommending dd-cfDNA testing in only 0.79 (95% confidence interval, 0.72 to 0.85) of validation cases. Combined GEP and dd-cfDNA testing validated higher area under the receiver operating characteristic curves than dd-cfDNA as a second-stage test for overall (0.85 [0.79 to 0.94] versus 0.82 [0.74 to 0.92]), antibody-mediated (0.96 [0.93 to 1.00] versus 0.90 [0.79 to 1.00]), and cellular rejections (0.69 [0.61 to 0.89] versus 0.63 [0.53 to 0.81]).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This staged approach reduces unnecessary biopsies and guides the efficient use of costly blood-based biomarkers while maintaining good clinical performance, particularly for subclinical anti","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":"1414-1428"},"PeriodicalIF":0.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147990751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}