Journal of The American Society of Nephrology最新文献

{"title":"Acetazolamide and Glomerular Hyperfiltration in Type 1 Diabetes: Additional Insights from Early Clinical Research.","authors":"Thierry Hannedouche","doi":"10.1681/asn.0000000780","DOIUrl":"https://doi.org/10.1681/asn.0000000780","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"16 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370261","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":"How Participatory Research Can Inform Antiracism Approaches to Advance Kidney Health Equity.","authors":"Abdou Simon Senghor,Godwin Okoye,Chandra L Ford,Deidra C Crews,Keith C Norris","doi":"10.1681/asn.0000000795","DOIUrl":"https://doi.org/10.1681/asn.0000000795","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"17 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335365","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":"Biomarkers of Kidney Failure and All-Cause Mortality in CKD.","authors":"Anthony Onoja,Thomas McDonnell,Isabelle Annessi,Rosamonde E Banks,Marianne Bergin,Paul Cockwell,Rodolphe Dusaulcy,Simon D S Fraser,Tim Johnson,Philip A Kalra,Barbara Lemaître,Moin Saleem,Phillipp Skroblin,Magnus Soderberg,Maarten W Taal,Robert J Unwin,Nicolas Vuilleumier,David C Wheeler,Nophar Geifman","doi":"10.1681/asn.0000000767","DOIUrl":"https://doi.org/10.1681/asn.0000000767","url":null,"abstract":"BACKGROUNDChronic kidney disease (CKD) carries a variable risk for multiple adverse outcomes, highlighting the need for a personalised approach. This study evaluated several novel biomarkers linked to key disease mechanisms to predict the risk of kidney failure (first event of eGFR <15 ml/min/1.73m2 or kidney replacement therapy), all-cause mortality, and a composite of both.METHODSWe included 2,884 adults with non-dialysis CKD from 16 nephrology centres across the UK. Twenty-one biomarkers associated with kidney damage, fibrosis, inflammation, and cardiovascular disease were analysed in urine, plasma, or serum. Cox proportional hazards models were used to assess biomarker associations and develop risk prediction models.RESULTSParticipants had mean age 63 (15) years, 58% were male and 87% White. Median eGFR 35 (25, 47) ml/min/1.73m2, and median urinary albumin-to-creatinine ratio (UACR) 197 (32, 895) mg/g. During median 48 (33, 55) months follow-up, 680 kidney failure events and 414 all-cause mortality events occurred. For kidney failure, a model combining three biomarkers (sTNFR1, sCD40, UCOL1A1) showed good discrimination (c-index 0.86, 95% CI: 0.83-0.89) but was outperformed by a model using established risk factors (age, sex, ethnicity, eGFR, UACR; c-index 0.90, 95% CI: 0.88-0.92). For all-cause mortality, a model using three biomarkers (hs-cTnT, NT-proBNP, suPAR) demonstrated equivalent discrimination (c-index 0.80, 95% CI: 0.75-0.84) to an established risk factor model (c-index 0.80, 95% CI: 0.76-0.84).For the composite outcome, the biomarker model discrimination (C-index 0.78, 95% CI: 0.76, 0.81) was numerically higher than for established risk factors (C-index 0.77, 95% CI: 0.74, 0.80), and the addition of biomarkers to the established risk factors led to a small but statistically significant improvement in discrimination (C-index 0.80, 95% CI: 0.77, 0.82; p value < 0.01).CONCLUSIONSRisk prediction models incorporating novel biomarkers showed comparable discrimination to established risk factors for kidney failure and all-cause mortality.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"25 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335381","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":"Endothelial Progenitor Cells: Disease Markers and Potential Therapy in Kidney Disease.","authors":"Shahd Al Heijani,Mohamed Naim Khalil,Salsabil Haque,LaTonya J Hickson,Amir Lerman,Lilach O Lerman","doi":"10.1681/asn.0000000792","DOIUrl":"https://doi.org/10.1681/asn.0000000792","url":null,"abstract":"Endothelial progenitor cells (EPCs) constitute a promising focus for research in regenerative medicine. These cells originate from the bone marrow and other circulating hematopoietic cells and regulate tissue regeneration and vascular integrity. EPCs mobilization serves for neovascularization and reendothelialization after injury in multiple organ systems, including the renal and cardiovascular systems. Both their number and function may vary in disease states like chronic kidney disease, depending on severity, comorbid conditions, and other factors. Therefore, circulating EPC count and function have been proposed as markers for vascular health, and their mobilization or replenishment may offer a potential therapy. Delivery of EPC has shown success in repairing injured kidneys in animal models of both chronic and acute kidney injury. This approach may be limited by EPC heterogeneity and incomplete characterization that may be addressed by standardization, engineering, or combination with other therapies. This article aims to review the current state and recent advances in our understanding of the role of EPC in homeostasis and conditions that may lead to their dysregulation in kidney diseases.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"268 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335378","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":"Cardiac LIM Protein, Kidney Fibrosis, and Vascular Change after Acute Cardiorenal Syndrome.","authors":"Yoshio Funahashi,Jessica F Hebert,Adam Munhall,Daiki Aomura,Kevin G Burfeind,Elizabeth D Nguyen,Tahnee Groat,Megan N Nickerson,Mahaba B Eiwaz,Jonathan W Nelson,Nicole K Andeen,Motoko Yanagita,Susan B Gurley,Michael P Hutchens","doi":"10.1681/asn.0000000774","DOIUrl":"https://doi.org/10.1681/asn.0000000774","url":null,"abstract":"BACKGROUNDHeart and kidney are bi-directionally interacting organs. Because heart and kidney disease are amongst the most common human diseases, investigating disease-causing interactions is important. Here, we identified a new role for cardiac-derived cardiac LIM protein, also known as cysteine-and-glycine-rich protein 3 (CSRP3), in acute cardiorenal syndrome.METHODSMice, both wild-type and genetically-altered to remove CSRP3 from the myocardium, were subjected to a model of acute cardiorenal syndrome, cardiac arrest and cardiopulmonary resuscitation (CA/CPR), or ischemia-reperfusion injury. Recombinant CSRP3 was administered to mice subjected to ischemia-reperfusion injury, and CSRP3 uptake in the kidney was inhibited by pharmacologic means.RESULTSWe found that CSRP3 transits the plasma after CA/CPR, and determined a kidney disease-modifying mechanism in which CSRP3 underwent megalin-dependent endocytosis in the renal proximal tubule and subsequently drove kidney fibrosis. Administration of CSRP3 to mice experiencing kidney injury exclusive of heart injury reproduced the kidney phenotype observed in CA/CPR mice. Genetic deletion of cardiac CSRP3 or proximal tubule megalin ameliorated cardiac arrest-induced chronic kidney injury. Translationally-relevant pharmacologic megalin inhibition also ameliorated CSRP3-mediated kidney phenotypic change, and administration of CSRP3 caused transcriptional change in the kidney.CONCLUSIONSWe describe the endocrine role of cardiac CSRP3 in a previously unknown heart-kidney interaction which directs specific kidney dysfunction and renovascular remodeling after cardiac injury. These investigations elucidate a novel facet of the intricate coupling between heart and kidney after acute cardiorenal syndrome.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"32 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328682","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":"Discontinuation of Renin-Angiotensin System Inhibitors during Acute Kidney Injury Episode and All-cause Mortality: Target Trial Emulation Studies.","authors":"Sheng Nie,Yanqin Li,Yinfang Sun,Shan Chen,Xian Shao,Mingzhen Pang,Shiyu Zhou,Licong Su,Ruixuan Chen,Fan Luo,Xin Xu,Fan Fan Hou,","doi":"10.1681/asn.0000000775","DOIUrl":"https://doi.org/10.1681/asn.0000000775","url":null,"abstract":"BACKGROUNDRenin-angiotensin system inhibitors (RASi) are widely used among patients with cardiovascular disease, diabetes, and chronic kidney disease, which are high-risk population for AKI. Evidence for the optimal management of RASi during an episode of acute kidney injury (AKI) is lacking.METHODSWe conducted a multi-database cohort study using sequential target trial emulation framework from the China Renal Data System (CRDS) and Medical Information Mart for Intensive Care IV (MIMIC-IV) databases. Adult patients with hospital-acquired AKI who had been receiving angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) treatment for at least 90 days were included. The primary outcomes were 30-day and 180-day all-cause mortality. Adjusted cumulative incidences and risk differences were estimated using weighted pooled logistic regression models.RESULTSA total of 27,003 person-trials were identified from the CRDS database (median [IQR] age, 70 [58-78] years; 12,972 [60%] male) and the MIMIC-IV database (median [IQR] age, 73 [63-82] years; 2825 [53%] male). The adjusted cumulative incidence of 30-day all-cause mortality was lower among person-trials with RASi discontinuation within two days after the hospital-acquired AKI than continuation (4.36% vs. 5.91%), with a risk difference of -1.55% (95% confidence interval [CI], -2.43% to -0.55%). Discontinuation of RASi was consistently associated with lower risk of all-cause mortality in the MIMIC-IV database, with similar beneficial associations observed across stratified analyses and multiple sensitivity analyses.CONCLUSIONSIn this study, stopping RASi within the first two days of AKI detection was associated with a lower risk of all-cause mortality.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"600 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144320299","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":"Use of eGFR Slope Thresholds as End Point Components in a Kidney Disease Progression Hierarchical Composite End Point.","authors":"Niels Jongs,Samvel B Gasparyan,Lars Frison,Patrick Schloemer,Meike Brinker,Dustin J Little,Hiddo J L Heerspink","doi":"10.1681/asn.0000000766","DOIUrl":"https://doi.org/10.1681/asn.0000000766","url":null,"abstract":"BACKGROUNDWe developed and validated a kidney disease progression hierarchical composite end point (HCE) combining time-to-event end points with the rate of estimated glomerular filtration rate (eGFR) decline (eGFR slope) as a continuous end point. An alternative to this continuous end point is to apply various thresholds on an absolute and relative scale for the pairwise comparisons in the eGFR slope component. We assessed the impact of different thresholds on the treatment effects and statistical power on the kidney disease progression HCE analyzed using win odds.METHODSWe calculated the win odds in seven international phase 3 CKD trials and compared treatment effects for the original HCE versus HCEs with different eGFR thresholds (0.5, 0.75, or 1.0 mL/min/1.73m2/year eGFR slope difference), as well as categorical thresholds and thresholds determined by percent differences in eGFR slope. In addition, we estimated the statistical power for these thresholds using a bootstrap sampling procedure to evaluate their impact on trial efficiency.RESULTSFor the seven CKD trials, the win odds estimate remained consistent, combined with a minor reduction in statistical power regardless of which eGFR thresholds were applied. For instance, for thresholds 0 (original HCE), 0.5, 0.75, and 1.0 the win odds of the DAPA-CKD trial were 1.41 (95% CI; 1.32, 1.52), 1.41 (95% CI; 1.31, 1.51), 1.40 (95% CI; 1.31, 1.51) and 1.40 (95% CI; 1.30, 1.50) with 97%, 92%, 92%, and 93% statistical power for a sample size of 500, respectively.CONCLUSIONSOur findings suggest that using eGFR thresholds in the kidney disease progression HCE did not alter treatment effect estimates and had only a minimal effect on statistical power compared to its continuous use.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"66 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144311371","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":"Acute Cisplatin Nephrotoxicity, Sodium-Glucose Cotransporter 2 Inhibitors, and Benefits Beyond Magnesium.","authors":"Chintan V Shah","doi":"10.1681/ASN.0000000762","DOIUrl":"https://doi.org/10.1681/ASN.0000000762","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310089","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":"LARP7 Protects Vascular Smooth Muscle Cell Contractile Phenotype in CKD by Coupling with P300.","authors":"Heng Wu, Cailing Su, Ansheng Cong, Ziyu Zhao, Shuang Cui, Chunyi Wu, Zhijie Huang, Yuxin Xie, Zuoyu Hu, Zhanmei Zhou, Lei Zhang, Fan Fan Hou, Wei Cao","doi":"10.1681/ASN.0000000761","DOIUrl":"https://doi.org/10.1681/ASN.0000000761","url":null,"abstract":"<p><strong>Background: </strong>Loss of vascular smooth muscle cell (VSMC) contractile phenotype complicates chronic kidney disease (CKD) and associates with cardiovascular pathologies. Here, focusing on vascular calcification and atherosclerosis, we tested the role of La Ribonucleoprotein 7 (LARP7) in maintaining VSMC contractile phenotype and mitigating CKD-associated vascular pathologies.</p><p><strong>Methods: </strong>Single-cell RNA sequencing and immunostaining analysis were used to investigate the association between LARP7 and contractile phenotype in VSMCs from CKD patients. In vivo and in vitro models evaluated the expression profile of LARP7 in CKD, and its contribution to VSMC dedifferentiation and progression of vascular calcification and atherosclerosis.</p><p><strong>Results: </strong>We demonstrated that LARP7, abundantly expressed in normal VSMCs, was downregulated in patients with CKD, associated with loss of VSMC contractile phenotype. This was corroborated in mouse model of CKD and in human VSMCs treated with CKD serum. Gain- and loss of-function in vitro studies demonstrated that LARP7 acted as an endogenous positive regulator of VSMC contractile phenotype through its interaction with P300. The LARP7-P300 interaction augmented P300 histone acetyltransferase activity and thereby enhanced H3K27 acetylation at contractile gene promoters. The CKD microenvironment impaired the LARP7-P300 interaction, reduced H3K27 acetylation at contractile gene promoters, facilitating VSMC transdifferentiation towards osteogenic and inflammatory phenotypes. Further in vivo studies demonstrated that restoration of LARP7 in CKD VSMCs reversed their phenotype switching, and thereby attenuated vascular calcification and atherosclerosis.</p><p><strong>Conclusions: </strong>Our study identified a novel role for LARP7 in maintaining VSMC contractile phenotype and mitigating CKD-associated vascular pathologies.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310091","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":"Authors' Reply: Acute Cisplatin Nephrotoxicity, Sodium-Glucose Cotransporter 2 Inhibitors, and Benefits Beyond Magnesium.","authors":"Weverton M Luchi, James A McCormick, Adriana C C Girardi","doi":"10.1681/ASN.0000000763","DOIUrl":"https://doi.org/10.1681/ASN.0000000763","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310090","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}