Journal of The American Society of Nephrology最新文献

{"title":"Structured Application of Genetic Testing in a Pediatric Kidney Clinic.","authors":"Jordy Salcedo-Giraldo,Krista R Wink,Nicholas Dadzie,Andrew Freiman,Tucker Pyle,Heather Gordish-Dressman,Marva Moxey-Mims,Neera K Dahl,Lisa M Guay-Woodford,Ashima Gulati, ","doi":"10.1681/asn.0000000816","DOIUrl":"https://doi.org/10.1681/asn.0000000816","url":null,"abstract":"BACKGROUNDThe expanding knowledge of identifiable genetic contributions to pediatric inherited kidney diseases and the increasing availability of genetic testing resources necessitate a combined nephrogenetics clinical approach. While such models are described for adults, the impact of a structured nephrogenetics workflow on children with inherited kidney disease has not been rigorously evaluated.METHODSClinical and genetic data of patients aged <1 - 21 years a 10-year period between 2014-2024 from a single-center pediatric inherited kidney disease outpatient program was evaluated. Genetic variants were classified as pathogenic/likely pathogenic and variants of uncertain significance (VUS). Patients were grouped into 'informative' or 'uninformative' groups based on the impact of genetic test results on disease management and outcomes.RESULTSOf the N=356 patients evaluated for a known or suspected inherited kidney disease, N=188 received clinical genetic testing. Of these, N=147 had an 'informative' genetic test affecting at least one positive clinical outcome. Patients with an 'informative' genetic test mostly harbored a pathogenic/likely pathogenic variant (N=122). An additional N=25 had a VUS re-classified as a 'VUS-of-interest' affecting a positive outcome measure. Genetic test results led to change in clinical diagnosis (reverse phenotyping, 46%), informed specific diagnosis-based treatment (46%), avoided unnecessary immunosuppression (27%) or kidney biopsy (18%) and guided extrarenal evaluation (72%) in patients with an informative test. Patients with a glomerular (OR=5.23, 95% confidence interval (CI) 1.96-13.96 ) or a tubular functional disease (OR=2.17, 95% CI 1.31-5.59) were more likely and those with a structural kidney disease (OR=0.39, 95% CI 0.25-0.60 ) were less likely to receive a genetic test when compared to all other disease categories combined.CONCLUSIONSThis workflow integrated multidisciplinary care for children with inherited kidney disease and describes a model for actionable clinical care plans after genetic testing. Informative genetic tests were associated with positive outcomes and notable challenges include access to combined nephrology and genetics expertise for informed testing and an effective result return including VUS interpretation.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"219 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737353","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":"Overexpression of Thrombomodulin in Adipose-Derived Mesenchymal Stem Cells Reduces Thrombogenic Risk and Enhances Therapeutic Efficacy.","authors":"Yoshiki Tanaka, Ayumu Nakashima, Naoki Ishiuchi, Kisho Miyasako, Keisuke Morimoto, Maria Yoshida, Kensuke Sasaki, Satoshi Maeda, Go Matsuda, Takao Masaki","doi":"10.1681/ASN.0000000810","DOIUrl":"10.1681/ASN.0000000810","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715095","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":"Keratin 20 Suppresses Exosomal Secretion of Peroxiredoxin 2 and Ferroptosis in Acute Kidney Injury.","authors":"Lijun Yin, Zebin Deng, Jiachen Liu, Lin Ye, Jun Huang, Yingbo Dai, Yinhuai Wang, Yu Li, Xuejing Zhu, Yu Lu, Yong Wu, Baiyu Feng, Yunhui He, Dongshan Zhang, Shaobin Duan, Zheng Dong, Fei Deng, Anqun Chen","doi":"10.1681/ASN.0000000805","DOIUrl":"10.1681/ASN.0000000805","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715094","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":"Sodium-Glucose Cotransporter 2 Inhibitors: Guarding Against Cisplatin-Associated Magnesium Wasting and Kidney Injury.","authors":"Andrew J Nickerson,Evan C Ray","doi":"10.1681/asn.0000000806","DOIUrl":"https://doi.org/10.1681/asn.0000000806","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"115 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693501","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":"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}