Journal of The American Society of Nephrology最新文献

{"title":"Correction to: p21-Activated Kinase 4 and Ischemic Acute Kidney Injury in Mice and Humans.","authors":"Hwang Chan Yu, Byeoung Hoon Chung, Yoejin Kim, Yoonji Lee, Hyunchae Sim, Sangkyu Lee, Hong Pil Hwang, Hee Chul Yu, Seunggyu Jeon, Han-Joo Maeng, Dongyun Shin, Kyung Pyo Kang, Seung-Yong Seo, Eun Ju Bae, Byung-Hyun Park","doi":"10.1681/ASN.0000000818","DOIUrl":"10.1681/ASN.0000000818","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144612188","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":"Higher versus Lower Phosphate Targets for Patients Undergoing In-Center Hemodialysis: A Randomized Controlled Trial.","authors":"Daniel Edmonston,Tamara Isakova,Laura M Dember,Sophia Waymyers,Davy Andersen,Kevin E Chan,Hrishikesh Chakraborty,Myles Wolf","doi":"10.1681/asn.0000000765","DOIUrl":"https://doi.org/10.1681/asn.0000000765","url":null,"abstract":"BACKGROUNDSerum phosphate targets in maintenance hemodialysis are based on observational studies. The HiLo trial aimed to compare the effect of a higher versus a lower phosphate target on clinical events in patients receiving maintenance hemodialysis.METHODSHiLo was a pragmatic, multicenter randomized trial that compared higher (≥6.5 mg/dl; \"Hi\") versus lower (<5.5 mg/dl; \"Lo\") phosphate targets in patients undergoing maintenance hemodialysis. The goal was to enroll 4400 cluster-randomized patients to assess the primary hierarchical composite outcome of all-cause mortality, followed by all-cause hospitalization using the win ratio. Due to an imbalance in baseline serum phosphate between groups, raising concern for biased recruitment due to post-randomization consent, HiLo transitioned to individual randomization 23 months after the trial began. Ultimately, HiLo was stopped early due to insufficient enrollment and inadequate phosphate separation between groups. For this report, we combined the cluster- and individually randomized cohorts, analyzing the individually randomized cohort as two additional clusters and applying a variance inflation factor to account for site-level clustering effects.RESULTSBetween March 2020 and November 2023, 352 patients in the Hi group and 441 in the Lo group were enrolled. After a median follow-up of 1.4 years (quartiles 1, 3: 0.5, 2.8 years), there were 11 deaths per 100 person-years in the Hi group and 13 per 100 person-years in the Lo group. The Hi group experienced 134 hospitalizations per 100 person-years compared to 96 per 100 person-years in the Lo group. The primary hierarchical composite outcome did not differ between groups (win ratio for Hi versus Lo targets was 0.97; 95% confidence interval, 0.55-1.71).CONCLUSIONSInsufficient enrollment and inadequate phosphate separation between groups preclude inferences about the effects of phosphate targets on clinical outcomes.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"92 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603790","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":"Time to Plan for Continuous Glucose Monitoring in Dialysis-Dependent Kidney Failure.","authors":"Klara R Klein,Jennifer E Flythe","doi":"10.1681/asn.0000000794","DOIUrl":"https://doi.org/10.1681/asn.0000000794","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"10 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603679","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":"Identification of Renal Transcripts Associated with Kidney Function and Prognosis in ANCA-Associated Vasculitis.","authors":"Benoît Brilland,Jérémie Riou,Thomas Quéméneur,Cyrille Vandenbussche,Nathalie Merillon,Andrea Boizard-Moracchini,Maëva Roy,Maïa Despré,Giorgina Barbara Piccoli,Assia Djema,Nicolas Henry,Laurence Preisser,Odile Blanchet,Viviane Gnemmi,Marie-Christine Copin,David Langlais,Pascale Jeannin,Patrick Blanco,Yves Delneste,Jean-François Augusto, ","doi":"10.1681/asn.0000000779","DOIUrl":"https://doi.org/10.1681/asn.0000000779","url":null,"abstract":"BACKGROUNDANCA-associated vasculitis with glomerulonephritis (AAV-GN) frequently progresses to kidney failure. However, tools for risk stratification of kidney outcomes remain limited. Existing approaches inadequately capture the molecular complexity underlying kidney injury, despite its potential value to tailor therapeutic management. We explored whether kidney transcriptomics could identify molecular signatures linked to kidney outcomes.METHODSWe included 199 patients with AAV-GN from two multicenter biobanks, and 23 controls. Kidney biopsies were profiled using NanoString nCounter to assess the expression of 750 immune-related genes. We conducted differential gene expression analysis, pathway enrichment analysis, and immune cell infiltration estimation to explore associations with kidney function and survival. A 12-gene prognostic signature was developed via LASSO-penalized Cox regression and compared to established histological classifications (Berden classification, Renal Risk Score, and ANCA Kidney Risk Score) with robust internal validation.RESULTSAAV-GN demonstrated extensive immune dysregulation with 150 differentially expressed genes versus controls, highlighting complement activation, immune cell recruitment and activation, TGFβ signaling, and immunometabolism pathways. Immune cell infiltration was marked by increased macrophages, dendritic cells, neutrophils, and T cell subsets, reflecting broad immune activation. Initial eGFR correlated with the expression of 319 genes. A 12-gene signature (CLU, C3, LTF, FLT1, PLCG2, FES, PRKCD, TXNIP, SLC7A5, PTEN, NRBF2, NFATC1) was significantly more strongly associated with kidney survival than were established histological classifications (adjusted p-value < 0.0001). Both high and low expression of several immune pathways (especially lymphocyte trafficking) were associated with better outcomes compared to intermediate expression.CONCLUSIONSTranscriptomic analysis of kidney biopsies in AAV-GN identified 150 differentially expressed immune-related genes and led to the development of a 12-gene signature that correlated strongly with kidney survival, outperforming established histological classifications.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"109 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594027","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":"Clonal Hematopoiesis of Indeterminate Potential and Cardiovascular Events: Issues to be Further Explored.","authors":"Zhongzhen Wang,Peng Liu","doi":"10.1681/asn.0000000789","DOIUrl":"https://doi.org/10.1681/asn.0000000789","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"107 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594028","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: Clonal Hematopoiesis of Indeterminate Potential and Cardiovascular Events: Issues to Be Further Explored.","authors":"Yang Pan,Caitlyn Vlasschaert,Cassianne Robinson-Cohen,Tanika N Kelly,Matthew B Lanktree","doi":"10.1681/asn.0000000790","DOIUrl":"https://doi.org/10.1681/asn.0000000790","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"34 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594029","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":"Predictive Value of the Oxford Classification for the Effect of Glucocorticoid Therapy in IgA Nephropathy.","authors":"Sufang Shi,Ian S D Roberts,Zixuan Wang,Lei Jiang,Chen Tang,Jinwei Wang,Jicheng Lv,MuhGeot Wong,Sean J Barbour,Vlado Perkovic,Daniel Cattran,Hong Zhang, ","doi":"10.1681/asn.0000000796","DOIUrl":"https://doi.org/10.1681/asn.0000000796","url":null,"abstract":"BACKGROUNDThe Oxford Classification is widely accepted as a histopathology tool to predict kidney outcomes in IgA nephropathy. However, it remains unclear whether the MEST-C scores can predict therapeutic response. This study aims to determine the predictive value of MEST-C scores on the efficacy of glucocorticoid therapy using the TESTING trial.METHODS379 Chinese participants were enrolled in the TESTING trial, of whom 279 had kidney biopsy slides available for central pathology review. The primary outcomes were a composite of ≥40% reduction in eGFR, kidney failure, or death due to kidney disease. Multivariable Cox regression analysis was used to determine the effects of glucocorticoid therapy across pathological subgroups, and the interaction between glucocorticoid therapy and pathology scores was evaluated.RESULTSAmong 279 participants selected for this study, the median (IQR) time from kidney biopsy to randomization was 4 (3-7) months. The median (IQR) follow-up was 4.7 (3.0-6.4) and 5.1 (3.1-6.8) years for the placebo and glucocorticoid treated group. Glucocorticoid therapy showed benefits across all histological subtypes. Participants with crescents (C1/C2) showed a trend toward greater benefit from glucocorticoid therapy (C1/2: HR, 0.05 [95% CI, 0.008-0.3]; C0: HR, 0.6 [95% CI, 0.4-0.9]; P for interaction=0.4). Participants with hypercellularity within segmental sclerosis lesions (cellular segmental sclerosis) demonstrated a significant reduction in the risk of kidney failure compared to those without (HR, 0.2 [95% CI, 0.07-0.4] versus HR, 0.6 [95% CI, 0.4-1.0]; P for interaction=0.03). Analysis of local pathologists' scores of all 379 Chinese participants demonstrated a significantly greater benefit from glucocorticoid therapy in participants with crescents (C0: HR, 0.7 [95% CI, 0.4-1.2]; C1: HR, 0.3 [95% CI, 0.2-0.6]; C2: HR, 0.2 [95% CI, 0.08-0.7]; P for interaction=0.05).CONCLUSIONSPresence of crescents and cellular segmental sclerosis in IgA nephropathy patients was associated with a favorable response to glucocorticoid therapy.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"32 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578726","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":"Telomere Dysfunction in Renal Tubular Epithelial Cells Leads to Kidney Fibrosis.","authors":"Sarita Saraswati,Paula Martínez,Rosa Serrano,Diego Mejías,Osvaldo Graña-Castro,Ruth Álvarez Díaz,Juana María Flores,Maria A Blasco","doi":"10.1681/asn.0000000771","DOIUrl":"https://doi.org/10.1681/asn.0000000771","url":null,"abstract":"BACKGROUNDRenal tubular epithelial cells are the critical mediators of kidney fibrogenesis. Telomere dysfunction has been associated with kidney injury and fibrosis. However, the role of telomere dysfunction specifically in renal tubular epithelial cells in the onset and progression of kidney fibrosis remains poorly understood. TRF1 is a critical component of the telomeric protective complex known as shelterin and its deficiency results in telomere dysfunction.METHODSTo investigate the impact of telomere dysfunction on kidney injury and fibrosis, we generated mice depleted for the shelterin component TRF1 specifically in renal tubular epithelial cells.RESULTSGenetic ablation of Trf1 caused decline in kidney function accompanied by increased tubular injury and tubulointerstitial fibrosis eight weeks after TRF1 depletion, concomitant with excessive accumulation of extracellular matrix, cell cycle arrest at G2/M phase, and telomeric damage. Trf1Δ/Δ mice activated regenerative repair mechanisms, supporting proliferation-mediated telomere shortening in renal tubular epithelial cells. At humane endpoint, Trf1Δ/Δ mice displayed elevated urinary albumin-to-creatinine ratio (UACR), associated with augmented interstitial fibrosis and tubular atrophy eventually leading to chronic kidney disease. At the mechanistic level, we reported the unprecedented finding that Trf1 deletion upregulates the Ras-Raf-Mek-Erk, PI3k/Akt/mTOR, and p38 pathways.CONCLUSIONSOur study underlies a role of renal tubular epithelial cells in the development and progression of kidney fibrosis and chronic kidney disease induced by telomere dysfunction.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"30 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586689","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":"Neuroimmune Control of Inflammation in Acute Kidney Injury and Multiorgan Dysfunction.","authors":"Eibhlin Goggins,Hiro Inoue,Mark D Okusa","doi":"10.1681/asn.0000000813","DOIUrl":"https://doi.org/10.1681/asn.0000000813","url":null,"abstract":"The nervous and immune systems engage in critical bidirectional communication that influences both physiological regulation and disease progression. This review discusses the neuroimmune axis and its role in controlling inflammation in acute kidney injury (AKI) and multiorgan dysfunction. Central to this regulation is the inflammatory reflex pathway, which consists of sensory afferent and motor efferent arcs. The cholinergic anti-inflammatory pathway (CAP) suppresses inflammation via vagus nerve activation, norepinephrine release, and α7 nicotinic acetylcholine receptor (α7nAChR) signaling in macrophages. Inflammatory mediators activate the afferent vagus nerve, transmitting signals to the brain initiating an anti-inflammatory response. Vagus nerve stimulation (VNS) and pulsed ultrasound (pUS) activate the cholinergic anti-inflammatory pathway, and attenuate inflammation and protect against AKI. Specifically, pulsed ultrasound prior to kidney ischemia-reperfusion injury (IRI) reduces inflammation and preserves renal function in a cholinergic anti-inflammatory pathway-dependent manner. Beyond the cholinergic anti-inflammatory pathway, other organ systems receive direct vagal innervation and stimulation of these pathways leads to an anti-inflammatory effect and organ protection. Multiorgan neuroimmune communications, including lung-kidney interactions and the liver-brain-gut axis are discussed, emphasizing their relevance in systemic inflammatory conditions. The role of the inflammatory reflex pathway in sepsis is addressed, emphasizing its potential to modulate the dysregulated immune response contributing to multiorgan failure. Finally, the discussion covers the role of the sympathetic nervous system, particularly renal sympathetic nerve activity, in modulating renal function and inflammation in AKI. Understanding and targeting these neural circuits may offer novel therapeutic strategies for AKI and related conditions.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"47 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578727","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":"'Fly'ing Toward New Drugs to Treat Podocytopathies.","authors":"Melissa H Little, Aude Dorison","doi":"10.1681/ASN.0000000786","DOIUrl":"10.1681/ASN.0000000786","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1459-1461"},"PeriodicalIF":9.4,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560465","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}