Journal of The American Society of Nephrology最新文献

{"title":"Effects of Dapagliflozin on Health-Related Quality of Life in Patients with CKD.","authors":"Wisanne M Bakker,Hiddo J L Heerspink,Niels Jongs,Ricardo Correa-Rotter,Peter Rossing,Robert D Toto,David C Wheeler,John J V McMurray,Anna Maria Langkilde,Ron T Gansevoort,Glenn M Chertow,Priya Vart","doi":"10.1681/asn.0000000776","DOIUrl":"https://doi.org/10.1681/asn.0000000776","url":null,"abstract":"BACKGROUNDTreatment with the sodium-glucose cotransporter 2 (SGLT2) inhibitor, dapagliflozin, attenuates progression of kidney disease and reduces the risks of heart failure and death in patients with chronic kidney disease (CKD). Data on the effects of dapagliflozin on health-related quality of life (HRQoL) are limited.METHODSAdults with CKD, with and without type 2 diabetes, with estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m2 and urinary albumin-to-creatinine ratio 200-5000 mg/g were randomized to dapagliflozin (10 mg/day) or placebo. We assessed HRQoL using the Kidney Disease Quality of Life (KDQOL-36) questionnaire at baseline and at 12, 24, and 36 months. In this prespecified analysis, we determined the overall effects of dapagliflozin versus placebo.RESULTSA total of 4032/4304 (94%) randomized participants (mean age 62(12) years, 32% female) had information on KDQOL-36 at baseline. Mean scores on the physical health composite (PHC); mental health composite (MHC); and kidney disease symptoms, effects, and burden were similar between randomized groups at baseline. During a median follow-up of 2.3 (Interquartile range: 1.9, 2.6) years, mean scores were significantly higher in participants randomized to dapagliflozin for PHC (0.71 [95% CI: 0.30, 1.31]), MHC (0.62 [95%CI: 0.14, 1.11]) kidney disease symptoms (1.33 [95% CI: 0.57, 2.10]), kidney disease effects (1.34 [95% CI: 0.43, 2.26]) and kidney disease burden (1.46 [95%CI: 0.30, 2.62]). Participants randomized to dapagliflozin were significantly less likely to experience a clinically meaningful (≥10 units) decline in PHC relative to placebo (hazard ratio [HR] 0.84 (95% CI: 0.74, 0.96). Corresponding HRs for ≥10-unit decline in MHC, and kidney disease symptoms, effects, and burden were 0.95 (95% CI: 0.85, 1.07), 0.84 (95% CI: 0.75, 0.94), and 0.84 (95% CI: 0.72, 0.97) and 0.93 (95% CI: 0.84, 1.02), respectively.CONCLUSIONSIn participants with CKD with and without type 2 diabetes, treatment with dapagliflozin slowed the decline in physical health, reduced worsening of symptoms, and lessened the effect of kidney disease.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"672 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661830","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":"Genetic Variation and Ultrafiltration with Peritoneal Dialysis: A Genome-Wide Association Study.","authors":"Ian B Stanaway,Ines P D Costa,Simon J Davies,Jeffrey Perl,Mark Lambie,Johann Morelle,Gail P Jarvik,Arsh K Jain,Jonathan Himmelfarb,Olof Heimburger,David W Johnson,James Pirkle,Bruce Robinson,Peter Stenvinkel,Angela Yee-Moon Wang,Olivier Devuyst,Rajnish Mehrotra, ","doi":"10.1681/asn.0000000803","DOIUrl":"https://doi.org/10.1681/asn.0000000803","url":null,"abstract":"BACKGROUNDThere is a large person-to-person variability in ultrafiltration volume with peritoneal dialysis (PD), most of which cannot be accounted for by demographic and clinical differences. Herein we tested the hypothesis that common genetic variants are associated with peritoneal ultrafiltration and explored one mechanistic pathway identified by genetic studies.METHODSWe generated estimates of heritability and undertook genome-wide and gene-wise studies, adjusted for peritoneal solute transfer rate (PSTR), to test associations of genetic variation with ultrafiltration on peritoneal equilibration test (PET) done at PD initiation in 2723 participants in the international Bio-PD study. We used a mouse model of PD to study the mechanistic basis for the association of PTGES gene with peritoneal ultrafiltration.RESULTSPET was done at a median of 61 days (IQR 38-118) from PD start with a median 4-hour ultrafiltration volume of 250 mL (IQR 25-465). The heritability of peritoneal ultrafiltration was estimated to be 50% (p=0.001). In single nucleotide variant (SNV)-wise multi-ancestry GWAS using TRACTOR software, one SNV reached genome-wide significance in participants with European local ancestry (rs72631501, CRK intron, p=2.6x10-8) and one in participants with South Asian local ancestry (rs1416265, intergenic, p=4.2x10-8). Gene-wise analyses showed significant association of 21 genes at false discovery rates (FDRs) <0.10 in the European strata, notably PTGES (FDR=0.053), SLC24A3 (FDR=0.0003) and CRK (FDR=0.04). SLC24A3 remained significant (FDR=0.03) in meta-analysis of the four ancestry strata. Using scRNAseq, PTGES localized in peritoneal adipocytes. In a mouse PD model, pharmacological modulation of PTGES altered dialysate prostaglandin E2 (PGE2) levels with changes in adipocyte volume, peritoneal small solute transfer rate, and ultrafiltration volume.CONCLUSIONSCommon genetic variants accounted for a substantial proportion of the variability in peritoneal ultrafiltration with potential associations with 21 genes, including CRK, PTGES and SLC24A3. Functional studies substantiated a potential role for PTGES/PGE2 in regulating peritoneal ultrafiltration.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"108 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645887","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":"Measurement, Estimation, and Correlates of the Glomerular Filtration Rate before and after Bariatric Surgery.","authors":"Allon N Friedman,Alex R Chang,Ling Ling Chuah,Guillaume A Favre,Caroline Grangeon-Chapon,Katie Lane,Yang Li,Carl W le Roux,John C Lieske,Enrique Morales,Esteban Porrini,Avry Chagnac","doi":"10.1681/asn.0000000797","DOIUrl":"https://doi.org/10.1681/asn.0000000797","url":null,"abstract":"BACKGROUNDImportant questions remain about how bariatric (i.e. weight loss) surgery affects measured glomerular filtration rate (mGFR) and estimated GFR (eGFR) as well as what factors influence change in mGFR post-surgery.METHODSData were pooled from all seven available studies (dates: 2004-2018) measuring GFR pre- and post-bariatric surgery using gold standard methods. Change in post-surgery mGFR, factors that influence change in mGFR, and effects on five GFR-estimating equations were analyzed using standard statistical methods.RESULTSThe cohort included 105 individuals from the US and Europe. 68% were female, 97% white, mean age was 50 years (range: 24-70), and mean BMI 46±8 kg/m2. Mean pre-surgery mGFR of 107 ml/min (range: 31-215) fell to 92 ml/min (-14%, 95% CI: -21, -10) post-surgery, with a strong linear relationship existing between pre-surgery mGFR and % change in GFR (r=-0.51; -0.64, -0.35). Individuals with pre-surgery mGFR ≥90, 60-<90, and <60 ml/min had -25 (-32, -19), 1 (-11, 13P=0.82), and 7 (0, 14) ml/min mean postoperative changes in mGFR. Change in weight was significantly correlated with change in mGFR (r=0.22; 0.03, 0.40). After adjusting for sex, changes in mGFR post-surgery were associated with higher pre-surgical age (-0.6 ml/min per year; -1.1, -0.2), mGFR (-0.5 ml/min per 1 ml/min; -0.6, -0.4) and change in systolic blood pressure (-0.3 ml/min per 1 mmHg; -0.6, 0.0). All GFR-estimating equations significantly underestimated post-surgical GFR reductions in people with preserved kidney function and had improved bias, precision and accuracy when de-indexed and applied to individuals with mGFR<90 ml/min.CONCLUSIONSIn individuals with obesity undergoing bariatric surgery the magnitude of post-surgical decline in mGFR is directly associated with pre-surgery GFR and only weakly correlated with weight loss. Additionally, GFR-estimating equations' performance improved when de-indexed and used in people with reduced kidney function, with the combined creatinine/cystatin C equations having the best overall performance.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"16 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639652","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":"Barriers to Patients Accessing Specialized Treatments for Glomerular Diseases.","authors":"Brian Monk,Brian Ewert,Andrew S Bomback,Keisha Gibson, ","doi":"10.1681/asn.0000000819","DOIUrl":"https://doi.org/10.1681/asn.0000000819","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"52 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144630356","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":"Preimplantation Histopathologic Assessment of Deceased Donor Kidneys: Recommendations from the Banff Time-Zero Biopsy Working Group.","authors":"Syed Ali Husain,Desley Neil,Adnan Sharif,Maarten Naesens,Parmjeet Randhawa, ","doi":"10.1681/asn.0000000820","DOIUrl":"https://doi.org/10.1681/asn.0000000820","url":null,"abstract":"Transplantation using kidneys from deceased donors with marginal clinical characteristics is increasing to maximize access to transplant. Preimplantation biopsies of such kidneys are often obtained to determine the degree of chronic changes as an objective supplement to donor clinical based assessment of organ quality, particularly in the United States. There is conflicting evidence and heterogenous practice about how preimplantation biopsies should be performed, interpreted, and incorporated into organ disposition decisions. In 2022, The Banff Foundation for Allograft Pathology tasked its Time-Zero Biopsy Working Group with reviewing existing literature on preimplantation biopsies to prepare consensus recommendations on situations in which these biopsies should be performed and suggest best practices for improving reproducibility of biopsy readings. This workgroup report tabulates the Working Group's recommendations and identifies gaps that need to be filled to advance preimplantation biopsy clinical practice in donor selection. The major recommendations are that a preimplantation biopsy should only be performed when clinical assessment tools indicate that the kidney is unsuitable for utilization, that the clinical and preimplantation biopsy findings should be interpreted together for organ utilization decisions, and that digital whole slide images be promoted to facilitate setting up reporting networks of nephropathologists. Additional prospective studies using predictive modeling approaches are needed to optimize preimplantation biopsy criteria, sampling, interpretation, and incorporation into kidney allocation decisions.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"108 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144630357","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":"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}