Kidney international最新文献

{"title":"Oxidative Stress Potentiates a STAT1-APOL1 Feedforward Loop and Governs Disease Severity in APOL1-Mediated Kidney Disease.","authors":"Soichiro Nagata, Andrew Kumar, Patricia Bunda, Anupama Priyadarshini, Nathaniel Luciano, Paulina X Medina Rangel, Gabriel Lerner, John Pell, E M Tanvir, Xuefei Tian, Karen Ebenezer, Randy Luciano, Dennis G Moledina, Whitney Besse, Christopher E Pedigo, Gilbert Moeckel, Stefan Somlo, Madhav C Menon, Shuta Ishibe","doi":"10.1016/j.kint.2026.09.025","DOIUrl":"https://doi.org/10.1016/j.kint.2026.09.025","url":null,"abstract":"<p><strong>Introduction: </strong>Apolipoprotein L1 (APOL1) risk variants (G1 and G2) confer immunity against Trypanosoma infection but markedly increase susceptibility to progressive kidney disease. However, only a subset of biallelic risk-variant carriers develops disease progression, distinct from murine models. Here, we evaluated molecular drivers of progressive kidney disease using a model that reflected the low human disease penetrance.</p><p><strong>Methods: </strong>To investigate the heterogeneity of APOL1-mediated kidney disease, we generated novel APOL1 bacterial artificial chromosome transgenic mice with doxycycline-inducible systemic interferon-γ expression (G0- or G1-IFNγ mice). Podocyte-specific transcriptomics using translating ribosome affinity purification (TRAP-seq) and single-cell spatial transcriptomics via 10x Genomics Xenium In Situ platform was performed. Mechanistic validation and analysis of factors regulating APOL1 upregulation were conducted in primary podocytes and subsequently validated in mouse kidney and in human kidney biopsy specimens via immunofluorescence.</p><p><strong>Results: </strong>A subset of G1-IFNγ mice developed severe albuminuria and focal segmental glomerulosclerosis, which strongly correlated with the magnitude of APOL1 upregulation. By pairing TRAP-seq with single-cell spatial transcriptomic data, we identified mitochondrial dysfunction and JAK-STAT signaling as a central mediator of podocyte injury. In primary podocytes, APOL1 risk variants triggered mitochondrial-derived oxidative stress, establishing a self-amplifying STAT1-APOL1 feedforward loop that further enhances APOL1 expression and APOL1 oligomerization. This pathogenic loop was consistently enriched in podocytes from both G1-IFNγ mice and in kidney biopsy specimens from patients with APOL1-mediated focal segmental glomerulosclerosis, demonstrating translational relevance.</p><p><strong>Conclusions: </strong>Our findings suggest that biallelic risk variants initiate an oxidative stress-induced positive feedforward loop which promotes and sustains APOL1 upregulation and STAT1 phosphorylation, thereby contributing to disease susceptibility, severity and outcome.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety outcomes of semaglutide by chronic kidney disease severity in the FLOW trial.","authors":"Katherine R Tuttle, Margit R Andersen, Mustafa Arici, Ecenur Guder Arslan, Srikanth Bellary, Thomas Idorn, Linong Ji, Zdravko Kamenov, Naoki Kashihara, Kenneth W Mahaffey, Johannes F E Mann, Vlado Perkovic, Søren Rasmussen, Peter Rossing, Philip Andreas Schytz, L Sreenivasamurthy, Richard E Pratley","doi":"10.1016/j.kint.2026.09.026","DOIUrl":"https://doi.org/10.1016/j.kint.2026.09.026","url":null,"abstract":"<p><strong>Introduction: </strong>People with type 2 diabetes (T2D) and chronic kidney disease (CKD) often experience medication intolerance and side effects that worsen with lower estimated glomerular filtration rate (eGFR). This prespecified secondary analysis assessed the safety of semaglutide by baseline eGFR.</p><p><strong>Methods: </strong>FLOW (NCT03819153) was a double-blind, randomized, placebo-controlled trial testing the efficacy of subcutaneous semaglutide 1.0 mg once-weekly on a primary kidney outcome (50% or more eGFR reduction, kidney failure, or death due to kidney or cardiovascular causes) in participants with T2D and CKD. Safety data were collected selectively and included serious adverse events (SAEs), AEs leading to treatment discontinuation, and prespecified AEs of special interest (AESIs). In this descriptive assessment, systematically collected safety data were reported numerically by baseline eGFR.</p><p><strong>Results: </strong>Of 3533 participants, 1767 received semaglutide and 1766 received placebo. Fewer SAEs were reported with semaglutide than placebo across baseline eGFR subgroups (45.1% versus 50.4% in the 60 or more ml/min per 1.73 m² subgroup, and 56.4% versus 60.4% in the under 30 ml/min per 1.73 m² subgroup). SAEs related to infections and infestations; cardiac disorders; respiratory, thoracic and mediastinal disorders; and metabolism and nutrition disorders were generally less frequent with semaglutide than placebo, regardless of baseline eGFR. Treatment discontinuations due to AEs were higher with lower baseline eGFR across treatment groups (60 or more ml/min per 1.73 m²: semaglutide 11.2%, placebo 11.3%; under30 ml/min per 66 1.73 m²: semaglutide 18.8%, placebo 18.7%). Discontinuations specifically due to gastrointestinal AEs were reported more frequently with semaglutide (4.5%) than placebo (1.1%), regardless of baseline eGFR. Frequencies of AESI were similar between treatment groups across baseline eGFR subgroups.</p><p><strong>Conclusions: </strong>In this safety assessment, SAEs were reported less frequently with semaglutide than placebo, with corresponding patterns observed for treatment discontinuations and AESIs. No unexpected safety concerns were identified across the spectrum of eGFR represented in the FLOW trial.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Chronic Renal Insufficiency Cohort (CRIC) study measured hepcidin, cardiovascular, kidney and metabolic outcomes in chronic kidney disease.","authors":"Monique E Cho, Rupal C Mehta, Tom Greene, Jared L Hansen, Carol Sweeney, Alfred K Cheung, Myles Wolf, Hernan Rincon-Choles, Jesse Hsu, Dominic Raj, Sylvia E Rosas, James Lash, Chi-Yuan Hsu, Mirela Dobre, Mark L Unruh, Panduranga Rao, Nora Fino","doi":"10.1016/j.kint.2026.10.006","DOIUrl":"https://doi.org/10.1016/j.kint.2026.10.006","url":null,"abstract":"<p><strong>Introduction: </strong>Abnormal iron homeostasis plays a critical role in extra-hematopoietic disorders. The relationship of hepcidin, the master iron regulator, to clinical outcomes, has not been characterized in a large cohort of chronic kidney disease (CKD).</p><p><strong>Methods: </strong>To determine if plasma hepcidin level predicts cardiovascular (CV), kidney, and metabolic outcomes in patients with CKD, we studied 3826 patients enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. Hazard ratios for hepcidin tertiles were estimated from Cox Proportional Hazards regression for primary outcomes of incident heart failure (HF), end stage kidney disease (kidney failure) or halving of the estimated glomerular filtration rate (eGFR), and new onset diabetes or prediabetes. Secondary outcomes included atherosclerotic events and all-cause and CV mortality.</p><p><strong>Results: </strong>The median and interquartile range of plasma hepcidin level was 43 (22, 77) ng/mL. Higher plasma hepcidin levels were associated with older age, male sex, non-Hispanic Black race, diabetes, lower eGFR, higher albuminuria, increased plasma levels of iron indices, C-terminal fibroblast growth factor 23, and markers of inflammation (high-sensitivity C-reactive protein and interleukin-6). We found no association between plasma hepcidin level and the risk for incident HF or prediabetes/diabetes. However, compared to the middle tertile, the highest hepcidin tertile was independently associated with increased risk for kidney outcomes (hazard ratio 1.19; 95% confidence interval 1.09, 1.30) and atherosclerotic events (hazard ratio 1.34; 95% confidence interval 1.09, 1.64), while the lowest hepcidin tertile was associated with increased risk for all-cause and CV mortality in fully adjusted multivariable models including iron indices and inflammation.</p><p><strong>Conclusion: </strong>Both low and high plasma levels of hepcidin are associated with adverse clinical outcomes.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A study using the REIN registry suggests a statin therapy benefits for secondary prevention in patients receiving dialysis.","authors":"Pierre Letourneau, Laetitia Koppe, Cécile Couchoud, Solène M Laville, Antoine Gavoille, Mikail Nourredine","doi":"10.1016/j.kint.2026.09.027","DOIUrl":"https://doi.org/10.1016/j.kint.2026.09.027","url":null,"abstract":"<p><strong>Introduction: </strong>While statins are effective for cardiovascular prevention in the general population, their benefit in patients with CKD G5D (kidney failure treated by dialysis) remains uncertain. Previous randomized controlled trials included mixed populations for primary and secondary prevention while excluding patients with recent cardiovascular events, leaving a knowledge gap regarding statin effectiveness for secondary prevention immediately following an atherosclerotic cardiovascular disease (ASCVD) event. Here, we address this gap by providing real-world evidence.</p><p><strong>Methods: </strong>We conducted a landmark-based observational study, informed by the target trial framework using the French Renal Epidemiology and Information Network (REIN) registry and merged with data from the French national healthcare system database from 2010 to 2023. We included adults with CKD G5D who experienced an ASCVD event. We used inverse probability of treatment weighting to balance baseline characteristics between statin initiators and non-initiators, thereby estimating the average causal effect on all-cause mortality. Results focus on the relative and absolute risk difference and the life expectancy gain using delta restricted mean survival time (dRMST).</p><p><strong>Results: </strong>The study cohort included 5534 patients (median age: 75 years; 67% male). During the ten years of follow-up, statin use was associated with a reduced risk of mortality. The survival curves reached a maximum absolute difference at year four (risk difference -6.2% (95% CI: -10.2; -2.2); relative risk 0.88 [95% CI: 0.81; 0.96]). Life expectancy extended significantly over time with a mean survival gain of 69 days at five years (95% CI: 14-125) and reaching 135 days at ten years (95% CI: 31-239). No difference was identified between groups regarding hospitalizations for rhabdomyolysis or toxic hepatitis.</p><p><strong>Conclusions: </strong>In patients receiving dialysis, statin initiation following an ASCVD event is safe and associated with a modest-to-moderate ten-year cumulative survival benefit. While interpreted within observational limitations, this real-world evidence supports their use in this secondary prevention setting.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peritoneal dialysis induces hepatic metabolic stress as an instigator for systemic inflammation.","authors":"Fabian Eibensteiner, Rebecca Herzog, Michael Trauner, Cécile Philippe, Eva-Maria Patronas, Juan Manuel Sacnun, Isabel Joanna Sobieszek, Markus Unterwurzacher, Anja Wagner, Elisabeth Lang, Claudia Daniela Fuchs, Lisa Daniel-Fischer, Michael Boehm, Arvand Haschemi, Emmanuel Dauda Dixon, Hubert Scharnagl, Tatjana Stojakovic, Franz Koenig, Seth Leo Alper, Andreas Vychytil, Klaus Kratochwill, Christoph Aufricht","doi":"10.1016/j.kint.2026.09.028","DOIUrl":"https://doi.org/10.1016/j.kint.2026.09.028","url":null,"abstract":"<p><strong>Introduction: </strong>Peritoneal dialysis (PD) is a lifesaving therapy in patients with kidney failure, but results in daily intraperitoneal glucose administration corresponding to 50% of the recommended energy intake, most of which enters the portal circulation. As the impact of this glucose exposure on liver and metabolic health remains unclear, we explored hepatic and systemic metabolic effects of PD.</p><p><strong>Methods: </strong>Healthy mice and mice with chronic kidney disease (5/6 nephrectomy C57BL/6 aged 12-14 weeks) underwent seven weeks of PD. Combining morphologic studies, untargeted tissue proteomics, targeted plasma metabolomics and spatial transcriptomics, we assessed hepatic molecular and metabolic effects of PD. Gut- and gut-vascular barriers, systemic and hepatic lipopolysaccharide abundance and zonal transcriptional changes were assessed with multiplexed spatial single-cell analysis and transcriptomics.</p><p><strong>Results: </strong>Intraperitoneally administered glucose during PD was rapidly taken up by the liver and induced hepatic metabolic inflammation. Portal-venous glucose overload bypassing the gastrointestinal tract resulted in increased glucose-to-cholesterol shunting with elevated plasma cholesterol levels, despite the absence of hepatic steatosis or glycogen storage. Increased oxidative stress and endotoxin load were associated with reduced hepatic Kupffer cell numbers without increased gut permeability.</p><p><strong>Conclusions: </strong>Ours study found chronic hepatic metabolic stress induced by PD. Evidence of hepatic glucotoxicity and oxidative stress as instigators for systemic metabolic inflammation induced by PD suggests that similar pathologic mechanisms could also contribute to increased cardiometabolic risk on chronic PD.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Febrile renal pseudotumors revealing ANCA-associated vasculitis.","authors":"Oumaima Hourmati, Jean-Michel Correas, Marie Coudray, Marion Rabant, Idris Boudhabhay, Michael Padden, Philippe L E Moal, Aurélie Hummel, Marie-Sophie Meuleman","doi":"10.1016/j.kint.2026.09.019","DOIUrl":"https://doi.org/10.1016/j.kint.2026.09.019","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stress-Sensing Over TCR Recognition: γδ T-cell therapy for CMV infection after transplantation.","authors":"Julian J Freen-van Heeren","doi":"10.1016/j.kint.2026.09.022","DOIUrl":"https://doi.org/10.1016/j.kint.2026.09.022","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Technology-Supported Solutions to Improve Guideline-Informed Care for Kidney Disease: Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.","authors":"Jo-Anne Manski-Nankervis, Wisit Cheungpasitporn, Amit X Garg, Matthew P M Graham-Brown, Konstadina Griva, Lipika Samal, Paul E Stevens, Navdeep Tangri, Harriette G C Van Spall, Michael Cheung, Jennifer M King, Morgan E Grams, Michel Jadoul, Alan S Go","doi":"10.1016/j.kint.2026.09.015","DOIUrl":"https://doi.org/10.1016/j.kint.2026.09.015","url":null,"abstract":"<p><p>Implementation of guideline-informed care for the prevention, detection, and management of kidney disease remains suboptimal throughout the world. In November 2025, Kidney Disease: Improving Global Outcomes (KDIGO) held a Controversies Conference on the role of technology-supported solutions to improve guideline-informed care for people with or at risk for kidney disease and to identify priorities for research. There have been rapid advances in various technologies for earlier identification of people with kidney disease; risk stratification for adverse kidney, cardiovascular, and other clinical and patient-centered outcomes; and promotion of guideline-informed therapies, monitoring, and patient self-management. Still, there remain important considerations for how to optimize the use of such technologies for achieving care that is integrated, personalized, safe, and guideline-informed. The conference identified a range of lived experience, clinician, health care system, health policy, and technology-level factors that can influence the effectiveness of technology-supported solutions in improving guideline-informed care. Research priorities included developing and maintaining living guidelines; harmonizing and integrating guideline recommendations into clinical decision support solutions; generating evidence on the effectiveness and safety of technology-supported solutions that reduce disparities and preserve trust; developing and evaluating efforts that promote interoperability, feasibility and scalability of technologies across health care systems; developing more effective public-private partnerships and systematic use of validated health technology assessments; and clarifying the incremental value of emerging technologies involving sensor-derived biomarkers and integrated multimodal data. Strategies to optimize digital health technologies for promoting guideline-informed care were also delineated.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A pure 1-methyluric acid stone from heavy coffee intake","authors":"Estel-Anais Hubaud,Nathalie Lambeng,Christine Deffert,Nora Schwotzer","doi":"10.1016/j.kint.2026.09.012","DOIUrl":"https://doi.org/10.1016/j.kint.2026.09.012","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"26 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149092375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consensus statement from the International Society of Glomerular Disease for Certification of Centers of Excellence in Glomerular Disease","authors":"Ghada Ankawi,Alessia Fornoni,Sarah E. Panzer,Brad H. Rovin,Sharon Adler,Silke R. Brix,Laurel Damashek,Duvuru Geetha,Larry A. Greenbaum,Sangeeta Hingorani,Tobias B. Huber,J. Ashley Jefferson,Vivekanand Jha,Tingting Li,Adrian Liew,Liz Lightstone,Juan M. Mejia-Vilet,Angel Morales,Precil D. Neves,Sydney Chi Wai Tang,Purva Sharma,Lama Abdelnour,Santiago Alonso,Jonathan Barratt,Thomas Benzing,Peter Boor,Olivia Boyer,Annette Bruchfeld,Nicole Endlich,Kresimir Galesic,Oliver Gross,Michelle Hladunewich,Aleksandar Jankovic,Kenar Jhaveri,Lisa Kim,Andreas Kronbichler,Richard Lafayette,Nicholas Larkins,Rachel Lennon,Elena Levtchenko,Tej K. Mattoo,Louise Oni,Heather Reich,Dana Rizk,Candice Roufosse,Moin Saleem,Mario Schiffer,Christine Sethna,Hitesh Shah,Hernan Trimarchi,Suneel Udani,André Weinstock,Motoko Yanagita,Izabela Zakrocka,Nelson Zamora","doi":"10.1016/j.kint.2026.07.023","DOIUrl":"https://doi.org/10.1016/j.kint.2026.07.023","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"30 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}