Journal of The American Society of Nephrology最新文献

{"title":"Rationale for Targeting Complement to Mitigate Renal Transplant Ischemia-Reperfusion Injury.","authors":"Chrysanthos D Christou,Fayyad Jaradat,Jonathon Olsburgh,Steven Sacks,Theodoros Kassimatis","doi":"10.1681/asn.0000000826","DOIUrl":"https://doi.org/10.1681/asn.0000000826","url":null,"abstract":"Ischemia-reperfusion injury (IRI) is an unavoidable consequence of kidney transplantation and a major contributor to delayed graft function (DGF). DGF, traditionally defined as the need for dialysis within the first week post-transplant, is linked to inferior graft and patient outcomes, prolonged hospitalization, and higher health care costs. IRI begins with tissue hypoxia, which triggers an inflammatory response upon reperfusion. The renal tubule plays a critical role in complement synthesis, with local activation driving inflammation and graft immunogenicity more than circulating liver-derived complement. The lectin pathway is a key initiator of complement activation in hypoxic renal tubules, primarily through collectin-11's interaction with glycan ligands on hypoxic cells, with further amplification via the alternative pathway. Despite promising preclinical results, systemic complement inhibitors have not significantly improved DGF in clinical studies, likely due to inefficient targeting of ischemic renal tubules. Machine perfusion offers a novel approach to delivering therapeutics directly to donor kidneys. Notably, hypothermic machine perfusion has improved DGF rates and early graft outcomes. Emerging targeted delivery systems using extracellular vesicles or nanoparticle-based carriers also promise to deliver therapeutics to the sites of injury. Organ-targeted complement inhibition via machine perfusion or other targeted delivery systems represent compelling strategies for IRI prevention. Finally, multigenic xenografts engineered to prevent complement activation have shown initial promise in overcoming the complement-mediated barriers that continue to challenge allotransplantation in humans.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"15 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684135","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":"Statins' Efficacy Controversy in Kidney Failure: Reassessing Safety and Dialysis Stratification Need.","authors":"Jiaru Lin,Lin Luo","doi":"10.1681/asn.0000000798","DOIUrl":"https://doi.org/10.1681/asn.0000000798","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"20 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684136","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: Statins' Efficacy Controversy in Kidney Failure: Reassessing Safety and Dialysis Stratification Need.","authors":"Franco Wing Tak Cheng,Wanchun Xu,Sydney Chi Wai Tang,Eric Yuk Fai Wan","doi":"10.1681/asn.0000000800","DOIUrl":"https://doi.org/10.1681/asn.0000000800","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"52 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684118","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":"Anemia and Methodological Nuances: Enhancing Cerebral Oxygenation Assessment in Intradialytic Exercise.","authors":"Yuchang Wang,Xinle Xie,Wu Yu,Qingyun Lv","doi":"10.1681/asn.0000000801","DOIUrl":"https://doi.org/10.1681/asn.0000000801","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"25 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144678104","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 Epigenetic Regulators of Vascular Calcification with a CRISPR-Based Screen.","authors":"Yaxin Lian,Chen Xie,Minjia Feng,Huijin Zhu,Xin Chen,Xiaolin Liu,Yun Kong,Dayu He,Jianshuai Ma,Yuxi Chen,Huanji Zhang,Aoran Huang,Yanlian Chen,Hui Huang","doi":"10.1681/asn.0000000793","DOIUrl":"https://doi.org/10.1681/asn.0000000793","url":null,"abstract":"BACKGROUNDVascular calcification, mainly driven by osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs), is a common pathological condition in patients with chronic kidney disease. However, the roles of other epigenetic regulators in this process remain largely unexplored. CRISPR screen is a highly efficient strategy widely used in identifying genes related to various biological processes. However, the lack of suitable cell sorting strategies combined with CRISPR screen meant this technology had not been applied to gene screening in vascular calcification.METHODSWe performed an epigenetic-focused CRISPR screen in primary human VSMCs and identified key genes and pathways underlying osteogenic transdifferentiation, based on sgRNA enrichment in RANKL + (calcified) and RANKL - (noncalcified) VSMCs isolated by magnetic activated cell sorting. To validate the screen results, potential genes with different rankings were validated by siRNA intervention and Alizarin Red S staining. Integrating CRISPR results with transcriptome data revealed 17 critical regulators. We further investigated the top hit, Anthrax Toxin Receptor 1 (ANTXR1), in vascular calcification by examining clinical human samples and intervention in mice model.RESULTSThrough CRISPR screen, we identified 122 potential genes positive-regulating vascular calcification and 116 negative-regulating genes. Phenotypic experimental results further verified the roles of genes with different rankings in osteogenic transdifferentiation of VSMCs, reinforcing the validity of our CRISPR screen system. Notably, integrative analysis of CRISPR screen with transcriptome data revealed ANTXR1 as a critical factor regulating vascular calcification. Furthermore, detection of clinical human samples confirmed the upregulation of ANTXR1 during calcification. Knockdown of ANTXR1 suppressed vascular calcification in mice model; likewise, overexpression promoted vascular calcification and the osteogenic transdifferentiation of VSMCs.CONCLUSIONSOur epigenetic-focused CRISPR screen and transcriptome analysis identified critical epigenetic genes involved in vascular calcification.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"10 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661834","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":"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}