Journal of The American Society of Nephrology最新文献

{"title":"Addressing Disparities in ESKD Care: Insights from a Multicultural European Cohort.","authors":"Lucas Jacobs,Maria do Carmo Filomena Mesquita,Joëlle Nortier,Frédéric Collart","doi":"10.1681/asn.0000000713","DOIUrl":"https://doi.org/10.1681/asn.0000000713","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"19 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143861984","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: Addressing Disparities in ESKD Care: Insights from a Multicultural European Cohort.","authors":"Ashutosh M Shukla,Yi Guo,Rebecca Campbell-Montalvo,Serena Jingchuan Guo","doi":"10.1681/asn.0000000714","DOIUrl":"https://doi.org/10.1681/asn.0000000714","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"108 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143861988","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":"GIT ArfGAP2: A Cytoskeletal Safeguard in Podocytes: Suppressing Rac1 to Combat Glomerular Injury.","authors":"Shuta Ishibe,Xuefei Tian","doi":"10.1681/asn.0000000707","DOIUrl":"https://doi.org/10.1681/asn.0000000707","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"51 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143861990","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":"Network Interactions of Circulating FGF23, HRG-HMGB1, and Cardiac Disease in CKD.","authors":"Farzana Perwad,Elvis A Akwo,Arushi Singhal,Nicholas Vartanian,Larry J Suva,Peter A Friedman,Cassianne Robinson-Cohen","doi":"10.1681/asn.0000000710","DOIUrl":"https://doi.org/10.1681/asn.0000000710","url":null,"abstract":"BACKGROUNDGenome-wide association studies (GWAS) have identified numerous genetic loci associated with mineral metabolism markers but have exclusively focused on single-trait analysis. In this study, we performed a multi-trait analysis of GWAS (MTAG) of mineral metabolism, exploring overlapping genetic architecture between traits to identify novel genetic associations for fibroblast growth factor 23 (FGF23).METHODSWe applied MTAG to variants common to GWAS of 5 genetically correlated mineral metabolism markers in European-ancestry participants. We integrated UK BioBank GWAS for blood levels for phosphate, 25-hydroxyvitamin D, and calcium (n=366,484) and CHARGE GWAS for parathyroid hormone (n=29,155) and FGF23 (n=13,716). We then used supervised and unsupervised deep machine learning to identify novel associations between genetic traits and FGF23.RESULTSMTAG increased the effective sample size for mineral metabolism markers to n=50,325 for FGF23. After clumping, MTAG identified independent genome-wide significant SNPs for all traits, including 62 loci for FGF23. Many of these loci have not been previously reported in single-trait analyses. Through a functional genomics approach, we identified Histidine-rich glycoprotein (HRG) and high-mobility-group-box 1 (HMGB1) as master regulators of downstream canonical pathways associated with circulating FGF23, and both genes were highly enriched in hypertrophied cardiac tissue of deceased hemodialysis patients. In addition, we found DNMT3A was associated with uremic toxin, 8-Hydroxy-2-deoxyguanosine, a biomarker of DNA damage. In silico gene perturbation analysis revealed DNMT3A is protective in patients with heart failure caused by hypertrophied or dilated cardiomyopathy.CONCLUSIONSOur findings highlight the importance of MTAG analysis of mineral metabolism markers to boost the number of genome-wide significant loci for FGF23 to identify novel genetic traits. Functional genomics revealed novel networks that inform unique cellular functions and identified HRG-HMGB1 as key master regulators of FGF23 and cardiovascular disease in CKD.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"9 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846295","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":"Xenotransplantation: Current Understanding of the Mechanism of Immune Mediated Injury.","authors":"Vasishta S Tatapudi,Aprajita Mattoo,Tamar Schiff,Sapna A Mehta,Edward Y Skolnik,Robert A Montgomery","doi":"10.1681/asn.0000000745","DOIUrl":"https://doi.org/10.1681/asn.0000000745","url":null,"abstract":"The scarcity of transplantable organs represents a worldwide public health crisis, and as a result, thousands of people with end-stage kidney disease (ESKD) die waiting for a transplant each year. Xenotransplantation involves transplanting organs from an animal source into humans, offering a potential solution to this significant unmet need. Indeed, if there is a limitless supply of organs, many more patients who do not meet the current criteria for transplant eligibility could also be considered candidates. While there are examples of attempts to transplant animal tissues or organs into humans dating back over 300 years, none were successful due to cross-species immunologic incompatibility. Even so, significant advances in genetic engineering and the emergence of novel immunosuppressive agents have spurred impressive improvements in xenograft survival in preclinical studies involving nonhuman primates. Furthermore, recent reports of genetically modified pig kidney and heart xenotransplants in human decedents and living recipients on a compassionate use basis have provided impetus to advancing the field towards first-in-human trials. However, studies in nonhuman primates and humans thus far have described adaptive as well as innate immune-mediated xenograft injury. Understanding the mechanistic aspects of these responses at the cellular and molecular levels is critical to the development of targeted genetic modifications and innovative therapeutic strategies aimed at preventing rejection and inducing tolerance. Moreover, the physiological components of the bidirectional communication between the human host and pig xenograft must also be understood and manipulated. Here, we review the breakthroughs in renal xenotransplantation in the past few decades and highlight the immunologic hurdles that have yet to be overcome.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"6 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846279","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":"Long-Term Outcomes in Nephrotic Syndrome by Kidney Biopsy Diagnosis and Proteinuria.","authors":"David Pitcher,Fiona Braddon,Bruce Hendry,Alex Mercer,Jonathan Barratt,Retha Steenkamp,Katie Wong,A Neil Turner,Wu Gong,Daniel P Gale,Moin A Saleem","doi":"10.1681/asn.0000000610","DOIUrl":"https://doi.org/10.1681/asn.0000000610","url":null,"abstract":"BACKGROUNDThe UK Registry of Rare Kidney Diseases (RaDaR) Idiopathic Nephrotic Syndrome cohort includes adults and children with genetic nephrotic syndrome, Focal Segmental Glomerulosclerosis (FSGS) and minimal change disease. This study examines long-term patient outcomes as a function of kidney biopsy diagnosis and proteinuria control.METHODS2467 adults and 1599 children were followed to establish outcomes including eGFR slope and kidney survival by diagnosis, analysed as a function of proteinuria from disease onset for FSGS and minimal change disease. Enrollment began in 2010, with follow-up to September 2023. Index date for the survival analyses was date of disease onset.RESULTSThe cohort had median [IQR] follow up of 8.2 [4.3-13.1] years; 30% of patients reached kidney failure or died. 1303 patients had FSGS, 1153 minimal change disease, 105 monogenic nephrotic syndrome. Children showed relatively preserved mean kidney function at disease onset (eGFR>100 ml/min/1.73m2), compared to adults (FSGS 61ml/min/1.73m2; minimal change disease 76ml/min/1.73m2). Kidney survival probability (95% CI) at 10 years varied with diagnosis: Genetic 29% (20-38), FSGS 58% (55-61), minimal change disease 87% (85-89) with mean (SD) rates of eGFR loss -26.5 (34.7), -6.2 (14.3), and -1.9 (10.2) ml/min/1.73m2 per year respectively. FSGS 10-year kidney survival (95% CI) for 6-12 months lowest proteinuria value in complete remission (<0.3g/g), partial remission (0.3-3.5g/g) and no remission (>3.5g/g) was 88% (70-96). 65% (50-76) and 37% (26-48), respectively. Time-averaged proteinuria of <1.5g/g over 6-24 months from disease onset was associated with 90% 10-year kidney survival. For minimal change disease, patients' 10-year kidney survival (95% CI) stratified by 6-12 months lowest proteinuria value was: complete remission 89% (79-94), partial remission 75% (51-89), and no remission 64% (41-81). In FSGS and minimal change disease 10-year eGFR slope was strongly correlated with absolute levels of proteinuria.CONCLUSIONSKidney outcomes were poor in genetic nephrotic syndrome; in FSGS outcomes were strongly associated with proteinuria level. Minimal change disease patients had better proteinuria control than FSGS and had better outcomes at each proteinuria level.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"219 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849365","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":"Effect of Peer Mentorship on Hospitalizations among Patients Receiving Maintenance Hemodialysis: A Pragmatic Randomized Controlled Trial.","authors":"Ladan Golestaneh,Ryung S Kim,Christopher Roach,Keith C Norris,Aaron D Fox,Michal L Melamed,Kerri L Cavanaugh","doi":"10.1681/asn.0000000709","DOIUrl":"https://doi.org/10.1681/asn.0000000709","url":null,"abstract":"BACKGROUNDPatients receiving maintenance hemodialysis are hospitalized frequently, leading to disproportionate cost of care, and contributing to high morbidity and mortality.METHODSTo test the effectiveness of peer mentorship to reduce hospitalization rates among patients receiving hemodialysis we performed a multi-center, pragmatic, randomized, controlled trial. Two hundred patient participants receiving hemodialysis at high risk for hospitalization were enrolled, 140 in Bronx, NY and 60 in Nashville, TN. Of these, 101 were randomized to the peer-mentor intervention and 99 were randomized to usual care. The intervention consisted of trained mentors, patients receiving hemodialysis, placing weekly telephone calls to their assigned patient participant mentees over a 3-month period. During telephone calls, mentors listened, provided emotional and informational support, and promoted self-management. During the intervention period and up to 15 months later, patient participants were observed for incidence of the primary outcome: monthly counts of unplanned hospitalizations and emergency department (ED) visits.RESULTSThe mean age of all patient participants was 54 (SD 13) years, 100 (50%) were female, 110 (57%) were Black and 70 (39%) were Hispanic. The adjusted incidence rate ratio (aIRR) of primary outcome was not different between intervention vs. usual care in intention to treat analysis (aIRR 0.85; 95% CI 0.64,1.15). Pre-specified as treated analyses, with as treated defined by >20 minutes of telephone contact between mentor/mentee pairs, suggested effectiveness of peer mentoring (aIRR 0.60; 95% CI 0.47,0.76), and exploratory post-hoc analyses demonstrated differences in effectiveness by site and self-identified race of mentees.CONCLUSIONSPeer mentorship did not significantly reduce the rate of hospitalization or ED visits overall, but there may have been effectiveness among the following subgroups: those enrolled in Bronx, NY and those who self-identified as Black.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"8 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841052","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":"Deciphering Clonal Hematopoiesis of Indeterminate Potential: Methods, Mechanisms, and Implications for Kidney Diseases.","authors":"Zhi Yu,Caitlyn Vlasschaert,Pradeep Natarajan","doi":"10.1681/asn.0000000739","DOIUrl":"https://doi.org/10.1681/asn.0000000739","url":null,"abstract":"Chronic kidney disease (CKD) afflicts over 10% of US adults, with its prevalence increasing sharply with age. Clonal hematopoiesis of indeterminate potential (CHIP) is a common, genetically heterogeneous blood cell disorder characterized by the age-related clonal expansion of hematopoietic cells driven by leukemogenic somatic mutations yet without hematologic malignancy or dysplasia. While CHIP is a strong risk factor for future hematologic malignancy (estimated at ∼0.5% per year, compared to <0.1% for those without CHIP), it is also linked to twofold higher cardiovascular disease in epidemiologic, cell-based, and murine studies. However, more recent work has implicated CHIP with renal outcomes such as chronic kidney disease as well as acute kidney injury, independent of traditional risk factors. This review covers the observations and proposed hypotheses linking CHIP and kidney disease. The review also underscores the need for further research to elucidate the distinct pathways through which CHIP may contribute to CKD and its comorbidities, considering the heterogeneity within CKD stages and etiologies, as well as whether CHIP is a causal driver of kidney disease or a marker of aging and comorbidity. Finally, we discuss the potential of anti-inflammatory treatments to mitigate CHIP's adverse effects on kidney health, aiming to improve management strategies for patients with CHIP-associated kidney diseases.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"122 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841043","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: The Integrated RNA Landscape of Renal Preconditioning against Ischemia-Reperfusion Injury.","authors":"Johnsen Marc,Kubacki Torsten,Yeroslaviz Assa,Späth Martin Richard,Mörsdorf Jannis,Göbel Heike,Bohl Katrin,Ignarski Michael,Meharg Caroline,Habermann Bianca,Altmüller Janine,Beyer Andreas,Benzing Thomas,Schermer Bernhard,Burst Volker,Müller Roman-Ulrich","doi":"10.1681/asn.0000000738","DOIUrl":"https://doi.org/10.1681/asn.0000000738","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"5 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824774","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: The RNA-Protein Interactome of Differentiated Kidney Tubular Epithelial Cells.","authors":"Ignarski Michael,Rill Constantin,W J Kaiser Rainer,Kaldirim Madlen,Neuhaus René,Esmaillie Reza,Li Xinping,Klein Corinna,Bohl Katrin,Petersen Maike,Frese Christian K,Höhne Martin,Atanassov Ilian,Rinschen Markus M,Höpker Katja,Schermer Bernhard,Benzing Thomas,Dieterich Christoph,Fabretti Francesca,Müller Roman-Ulrich","doi":"10.1681/asn.0000000737","DOIUrl":"https://doi.org/10.1681/asn.0000000737","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"5 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824820","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}