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

{"title":"Urinary Biomarker Analysis of the SANCTUARY Trial: Insights into IgA Nephropathy Pathophysiology and Ravulizumab Mechanism of Action.","authors":"Tobin J Cammett, Ellen E Millman, Julio Luna, Kara Rice, Stephen Nolan, Youssef M K Farag, Richard Lafayette, Jonathan Barratt","doi":"10.2215/CJN.0000001243","DOIUrl":"https://doi.org/10.2215/CJN.0000001243","url":null,"abstract":"<p><strong>Background: </strong>Complement activation in IgA nephropathy (IgAN) drives inflammation, nephron loss, and progressive kidney damage. We evaluated urinary biomarkers among participants with IgAN treated with ravulizumab (terminal complement C5 inhibitor) versus placebo in the Phase 2 SANCTUARY trial and healthy donors.</p><p><strong>Methods: </strong>This exploratory analysis evaluated data from 60 participants with IgAN from SANCTUARY (NCT04564339) and 25 healthy donors. Spot urine samples were collected pre-dose on days 1, 15, 71, 127, and 183, and thereafter Q8W. Urinary biomarkers of complement activation (soluble C5b-9 [sC5b-9] and factor Ba), renal inflammation (CD163), and tubular injury (KIM-1, NGAL) were assessed, normalized to creatinine. Biomarkers were compared between subgroups: baseline 24-hour urine protein (1-2 vs >2 g/day) and eGFR (30-60 vs ≥60-90 vs ≥90 mL/min/1.73 m2). Ravulizumab and placebo groups were compared using mixed model for repeated measures (MMRM).</p><p><strong>Results: </strong>Baseline levels of sC5b-9/Cr, Ba/Cr, CD163/Cr, and KIM-1/Cr were significantly elevated in participants with IgAN versus healthy donors (P < 0.001 for all); 93% participants had elevated sC5b-9/Cr. Baseline sC5b-9/Cr, CD163/Cr, and KIM-1/Cr were significantly higher in participants with baseline urine protein >2 g/day versus 1-2 g/day (P < 0.05 for all). Baseline sC5b-9/Cr and Ba/Cr were highest in participants with eGFR 30-60 mL/min/1.73 m2 (P < 0.05 across subgroups). Significantly greater reductions in sC5b-9/Cr and Ba/Cr were observed with ravulizumab versus placebo at Weeks 2, 10, 18, and 26; in CD163/Cr and KIM-1/Cr at Weeks 10, 18, and 26 (MMRM; P < 0.05 for all). Reductions in these biomarkers were sustained through Week 50 and were observed after crossover from placebo to ravulizumab at Week 26.</p><p><strong>Conclusions: </strong>Ravulizumab led to early, sustained, and significant reductions in urinary biomarkers of complement activation and decreases in markers of renal inflammation and proximal tubular injury; this is consistent with its observed effect on proteinuria.</p>","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149248347","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":"Interpreting Outcomes After Early Continuous Renal Replacement Therapy Liberation with Caution.","authors":"Ruhaan Bajpai, Aetan Parmar","doi":"10.2215/CJN.0000001232","DOIUrl":"https://doi.org/10.2215/CJN.0000001232","url":null,"abstract":"","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149241128","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":"Effects of Aldosterone Synthase Inhibitor Baxdrostat on Albuminuria in CKD and Uncontrolled Hypertension.","authors":"Jamie P Dwyer, Robin Myte, Hiddo J L Heerspink, Glenn M Chertow, Noha Maklad, Brendon L Neuen, Dimitris Kardassis, Nataliia Zaozerska, Dustin J Little","doi":"10.2215/CJN.0000001248","DOIUrl":"https://doi.org/10.2215/CJN.0000001248","url":null,"abstract":"","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149241137","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":"Authors' Reply: Interpreting Outcomes after Early Continuous Renal Replacement Therapy Liberation with Caution.","authors":"Dana Y Fuhrman, Sean M Bagshaw, Katja M Gist, Stuart L Goldstein","doi":"10.2215/CJN.0000001241","DOIUrl":"https://doi.org/10.2215/CJN.0000001241","url":null,"abstract":"","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225662","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":"A Kidney Patient's Perspective on Incremental Peritoneal Dialysis and Shared Decision-Making.","authors":"Jan van Cruchten","doi":"10.2215/CJN.0000001259","DOIUrl":"https://doi.org/10.2215/CJN.0000001259","url":null,"abstract":"","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208382","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":"Estimating Residual Kidney Function in Hemodialysis Patients Using Serum Uromodulin.","authors":"David A Jaques, Valérie Jotterand Drepper, Nicola Marangon, Olivier Devuyst, Sophie De Seigneux, Patrick Saudan, Belen Ponte","doi":"10.2215/CJN.0000001247","DOIUrl":"https://doi.org/10.2215/CJN.0000001247","url":null,"abstract":"<p><strong>Background: </strong>Residual kidney function (RKF) monitoring is essential to safe incremental hemodialysis (HD) prescription. Yet the cumbersome nature of interdialytic urine collections represents a major barrier to routine implementation. We investigated serum uromodulin, as a marker of functional renal mass, in identifying HD patients with clinically significant RKF when used alone, or in combination with serum β2-microglobulin, a traditional marker of glomerular filtration.</p><p><strong>Methods: </strong>We conducted a prospective observational study of 151 HD patients at two centers in Geneva, Switzerland. Serum uromodulin and β2-microglobulin were measured on pre-dialysis samples, and residual urea clearance (KRU) was determined by interdialytic timed urine collection. The discriminative performance of each biomarker for identifying patients with KRU ≥2 mL/min/35L was assessed by receiver operating characteristic (ROC) analysis, and the two markers were then combined using logistic regression. We applied a two-threshold grey-zone strategy, defining a priori rule-out and rule-in cutoffs to achieve ≥90% sensitivity and specificity, respectively.</p><p><strong>Results: </strong>Of the 151 patients, 92 (61%) had KRU <2 mL/min/35L and 59 (39%) had KRU ≥2 mL/min/35L. Serum uromodulin discriminated KRU ≥2 mL/min/35L with an area under the curve (AUC) of 0.891 (95% CI 0.839-0.944), statistically equivalent to β2-microglobulin (AUC 0.877; P=0.66). Each marker contributed independent information: the combined model achieved an AUC of 0.923 (95% CI 0.883-0.964), superior to either alone (vs uromodulin P=0.03; vs β2-microglobulin P=0.01). Using the grey-zone strategy, uromodulin alone classified 76% of patients without urine collection (negative predictive value (NPV) 97%, positive predictive value (PPV) 84%), while the combined model classified 85%. Restricting analysis to non-anuric patients modestly decreased discrimination (AUC 0.833) with preserved PPV (84%), while avoiding the need for urine collection in 80% of this sub-group.</p><p><strong>Conclusions: </strong>Serum uromodulin provides RKF information orthogonal to and non-redundant with conventional filtration markers. Their combination reliably identifies the KRU ≥2 mL/min/35L threshold relevant to incremental hemodialysis, sparing most patients from urine collection.</p>","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198804","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":"National Trends in Deceased Donor Kidney Transplantation During the 2025 United States Transplant-System Safety and Allocation Oversight Period.","authors":"Stefan Reuter, J Sebastian Danobeitia, Klemens Budde","doi":"10.2215/CJN.0000001245","DOIUrl":"https://doi.org/10.2215/CJN.0000001245","url":null,"abstract":"","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198762","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":"Association of Life's Essential 8 with Risk of End-Stage Kidney Disease in the United Kingdom Biobank Study.","authors":"Chenxinan Ma, Mihir Gandhi, Tazeen H Jafar","doi":"10.2215/CJN.0000001240","DOIUrl":"https://doi.org/10.2215/CJN.0000001240","url":null,"abstract":"<p><strong>Background: </strong>Life's Essential 8 (LE8) is a comprehensive cardiovascular health (CVH) metric integrating eight behavioral and biological factors and has been associated with cardiovascular disease risk. However, evidence linking LE8 to end-stage kidney disease (ESKD) is lacking.</p><p><strong>Methods: </strong>We analyzed the United Kingdom (UK) Biobank data prospectively on participants who were free of ESKD at baseline. The LE8 score, calculated as the unweighted average of eight components (range, 0-100), was categorized as low (0-49), moderate (50-79), and high (80-100), with higher scores indicating more favorable health status. The primary outcome was incident ESKD, defined as needing kidney replacement therapy or reaching CKD stage G5. We used Cox proportional hazards models to estimate hazard ratios (HR) for incident ESKD, separately for LE8 categories and for continuous LE8 scores, with nonlinear associations assessed using restricted cubic splines (RCS). We also estimated population-attributable fractions (PAFs) for non-optimal LE8 and its subscales and components.</p><p><strong>Results: </strong>Among 276,494 participants (mean [SD] age 56 [8] years; 48% male; 95% White), 455 incident ESKD events occurred over a median follow-up of 14.1 years. In fully adjusted Cox models, each 10-point decrement in LE8 score was associated with higher ESKD risk (HR, 1.47; 95% CI, 1.34-1.60). Compared with high LE8, moderate LE8 was associated with a 2.1-fold higher risk of incident ESKD (HR, 2.11; 95% CI, 1.39-3.21), and low LE8 was associated with a more than five-fold higher risk (HR, 5.57; 95% CI, 3.42-9.07). Subscale analyses showed similar patterns. RCS analysis suggested nonlinear associations for overall LE8 and the biological subscale, with steeper risk gradients at lower scores. Blood pressure, blood glucose, physical activity, and smoking had statistically significant estimated PAF for incident ESKD, with the largest fractions observed for blood pressure and blood glucose.</p><p><strong>Conclusions: </strong>In this large prospective cohort, low LE8 was associated with a substantially higher risk of incident ESKD. These findings highlight the potential relevance of LE8-guided improvement in behavioral and biological factors for ESKD prevention.</p>","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198779","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":"Elusive Promises, Complex Realities: Dialysis Provider Perspectives on the Expansion of Medicare Advantage.","authors":"James B Wetmore","doi":"10.2215/CJN.0000001257","DOIUrl":"https://doi.org/10.2215/CJN.0000001257","url":null,"abstract":"","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148607","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":"Mainstream Genomic Testing in Nephrology: Evidence and Priorities for Evaluation.","authors":"Xavier Fernando Vela Parada","doi":"10.2215/CJN.0000001255","DOIUrl":"https://doi.org/10.2215/CJN.0000001255","url":null,"abstract":"","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149605","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}