Journal of The American Society of Nephrology最新文献

{"title":"Endothelin Receptor Antagonists in Patients with IgA Nephropathy Treated with Sodium-Glucose Cotransporter 2 Inhibitors.","authors":"Patrick H Nachman","doi":"10.1681/ASN.0000001198","DOIUrl":"10.1681/ASN.0000001198","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1861-1863"},"PeriodicalIF":9.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13567886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dialysis Access without Guesswork: A Digital Navigation Framework for Improved Access Technique.","authors":"Erin Moore, Jaime Haak, Paola Fernadez, Shannon Beardsley","doi":"10.1681/ASN.0000001267","DOIUrl":"10.1681/ASN.0000001267","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865625","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":"Modernizing Kidney Transplant Referral: Integrating eGFR with Kidney Failure Risk.","authors":"Amber B Paulus, Johanna Christensen, Nilang Patel, Scott Silvey, Dhiren Kumar, Rachel E Patzer, Navdeep Tangri, Gaurav Gupta","doi":"10.1681/ASN.0000001259","DOIUrl":"10.1681/ASN.0000001259","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818809","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":"Dialysis Discontinuation Rates at Low Levels of Kidney Function in Patients with Acute Kidney Injury on Intermittent Hemodialysis.","authors":"Ian E McCoy, Kathleen D Liu, Edward D Siew, Delphine S Tuot, Anitha Vijayan, Y Diana Kwong, Gonzalo Matzumura Umemoto, Bethany C Birkelo, John Neuhaus, Hanjing Zhuo, Chi-Yuan Hsu","doi":"10.1681/ASN.0000001245","DOIUrl":"10.1681/ASN.0000001245","url":null,"abstract":"<p><strong>Key points: </strong>Timed urine creatinine clearance was superior to urine output and eGFR for predicting ongoing dialysis requirement in AKI. Even patients with measured creatinine clearance of <10 ml/min had substantial likelihood of not requiring dialysis in the next 7 days.</p><p><strong>Background: </strong>Anticipating when dialysis can be discontinued for patients with AKI requiring dialysis (AKI-D) is a common, but challenging, clinical problem. While timed urine collection metrics such as creatinine clearance and urine output are often proposed to inform the decision, few studies have rigorously quantified the need for ongoing dialysis by level of creatinine clearance, particularly in the period after critical illness has resolved when competing risk of death drops and liberation from dialysis becomes a relatively higher clinical priority. We hypothesized that many patients would not require dialysis even at relatively low levels of residual kidney function ( e.g ., creatinine clearance less than 10 ml/min).</p><p><strong>Methods: </strong>In this ancillary study of the Liberation from Acute Dialysis (LIBERATE-D) trial intervention arm, timed urine collections blinded to clinicians were performed per protocol, and dialysis was performed for prespecified indications. Logistic regressions computed predicted probabilities of requiring dialysis in the subsequent 7 days by level of measured creatinine clearance, urea clearance, the average of creatinine and urea clearances, urine output, and eGFR calculated from serum creatinine. The fraction of patients requiring dialysis in the subsequent week at various thresholds of creatinine clearance and urine output were also reported.</p><p><strong>Results: </strong>Among 147 timed urine collections from 85 patients with AKI-D, median (interquartile range) creatinine clearance was 7.1 (3.1-15.9) ml/min and median urine output was 930 (471-1786) ml/d. Creatinine clearance demonstrated significantly higher discrimination (area under the receiver operating characteristic curve 0.84) than urine output (area under the receiver operating characteristic curve 0.78). Dialysis was not required in the subsequent week for 81% (22 of 27) of urine collections with creatinine clearance 10-20 ml/min and 44% (19 out of 43) with creatinine clearance 5 to <10 ml/min.</p><p><strong>Conclusions: </strong>In a clinical trial with protocolized dialysis indications for hemodynamically stable patients with AKI-D, patients with lower levels of kidney function, such as creatinine clearance of 5-10 ml/min, were often able to discontinue dialysis.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818729","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":"Pregnancy and Autosomal Dominant Polycystic Kidney Disease: A GENKYST Study.","authors":"Cecile Vigneau, Sophie Morice, Yannick Lemeur, Sahar Bayat","doi":"10.1681/ASN.0000001228","DOIUrl":"https://doi.org/10.1681/ASN.0000001228","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813351","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":"Renin Is Critical for Renin-Lineage Cell Plasticity, Migration, and Disease Outcome in Experimental Crescentic GN.","authors":"Shila Azizolli, Sagor Halder, Anne Steglich, Akua Annoh, Florian Gembardt, Irina Simonova, Jan Sradnick, Andreas Dahl, Rajinder Gupta, Stefan R Bornstein, Vladimir Todorov, Hannah Weissbach, Christian Hugo","doi":"10.1681/ASN.0000001239","DOIUrl":"10.1681/ASN.0000001239","url":null,"abstract":"<p><strong>Key points: </strong>Renin deficiency in renin-lineage cells worsened crescentic GN and was associated with lower glomerular cell migration. Loss of renin altered immune-associated, metabolic, and migratory transcriptional programs in renin-lineage cells. Renin-lineage cell ablation reduced macrophage/leukocyte infiltration but had limited effects on overall disease severity.</p><p><strong>Background: </strong>The adult juxtaglomerular renin-lineage cell niche demonstrates cellular plasticity after injury, but its role in highly inflammatory crescentic GN remains unclear. While renin-angiotensin signaling promotes fibrosis and inflammation, the contribution of the renin-lineage cells and renin expression within these cells to crescentic GN has not been investigated.</p><p><strong>Methods: </strong>We used tdTomato lineage tracing to track renin-lineage cells in wild-type (WT) and renin-knockout (RenKO) mice after crescentic GN induction. Renin-lineage cell migration and glomerular injury were quantified histologically. Single-cell RNA sequencing was performed on isolated tdTomato-positive cells on days 10 and 21 after injury to characterize transcriptional programs. Disease progression was additionally examined in mice with diphtheria toxin A-mediated renin-lineage cell ablation.</p><p><strong>Results: </strong>Renin-lineage cells were detected within injured glomeruli during crescentic GN. Genetic renin deletion worsened disease outcomes, with RenKO mice developing increased albuminuria (by 3-fold), crescent formation (by 50%), and podocyte loss (by 15%) by day 21 compared with WT controls. Renin-deficient renin-lineage cells exhibited reduced glomerular migration and decreased colocalization with mesangial cell markers. Single-cell transcriptomic analysis revealed distinct transcriptional programs between WT and RenKO renin-lineage cells, with RenKO cells enriched for IFN-stimulated and reduced migration-associated pathways. Renin-lineage cell ablation reduced macrophage infiltration but did not alter disease severity.</p><p><strong>Conclusions: </strong>Renin expression influenced migration and injury-associated responses of renin-lineage cells during crescentic GN. Loss of renin was associated with a dysfunctional IFN-driven and antimigratory phenotype together with more severe glomerular injury, whereas renin-lineage cell ablation reduced macrophage infiltration but had limited effects on overall disease severity.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813298","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":"Ciliary ARL13B Drives Cystogenesis in the Kidney by Its Guanine Nucleotide Exchange Factor Activity.","authors":"Robert E Van Sciver, Avery Forster, Leslie M Lewis, Tamara Caspary","doi":"10.1681/ASN.0000001238","DOIUrl":"10.1681/ASN.0000001238","url":null,"abstract":"<p><strong>Key points: </strong>Loss of ciliary ARL13B suppressed cystogenesis in the kidneys of an adult mouse model of polycystic kidney disease without ablating cilia. Loss of ciliary ARL13B or the residue critical for its guanine nucleotide exchange factor activity did not affect kidney morphology or physiology in an adult induced mouse model. Mutation of a residue critical for ARL13B activation of ARL3 suppressed cystic phenotypes in Pkd1 -dependent cysts.</p><p><strong>Background: </strong>Polycystic kidney disease (PKD) is the leading genetic cause of kidney failure, resulting in the accumulation of fluid-filled cysts and gross enlargement of the kidney. Mutations in PKD1 or PKD2 , which encode ciliary polycystin proteins, are the most common cause of PKD. These proteins function in a cilia-dependent cyst activation (CDCA) pathway-one that requires cilia for its procystic function-yet the molecular driver(s) of this pathway are unknown. ARL13B is a regulatory GTPase enriched in cilia and links to cystogenesis in the kidneys. ARL13B possesses guanine nucleotide exchange factor (GEF) activity for ARL3, another ADP-ribosylation factor-like family GTPase with links to cilia.</p><p><strong>Methods: </strong>We used 2 distinct Arl13b mouse alleles to investigate whether ARL13B is a component of the CDCA pathway: Arl13bV358A encodes for enzymatically normal ARL13B that is undetectable in cilia, and Arl13bR79Q encodes for cilia-localized ARL13B lacking a residue critical for its ARL3 GEF activity. We used these alleles in a Pkd1 -deficient adult mouse model and investigated kidney morphology (hematoxylin and eosin and cystic index analysis), physiology (BUN measurements), kidney fibrosis (picrosirius staining and α -smooth muscle actin levels), kidney injury (SRY box transcription factor 9 immuno-fluorescent staining and quantification), and Wnt signaling ( β -catenin and cyclin D1 protein levels).</p><p><strong>Results: </strong>We found that loss of ciliary ARL13B or mutation of a single residue critical for its ARL3 GEF activity suppressed Pkd1 -dependent cysts. We observed reductions in kidney size, cystic index, and BUN. We also observed suppression of kidney fibrosis, kidney injury, and β -catenin and cyclin D1 protein levels.</p><p><strong>Conclusions: </strong>Our results identified a subcellular location and mechanism driving Pkd1 -dependent cystogenesis in the kidneys. We demonstrated that expression of a critical residue for ARL13B's GEF activity specifically in cilia is a key mechanism of the CDCA pathway driving cystogenesis in the kidneys.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813324","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: Joint Interpretation of Long-Chain and Very Long-Chain Sphingolipid Associations with Mortality in Hemodialysis.","authors":"Benjamin Lidgard, Paul N Jensen, Colleen M Sitlani, Rozenn N Lemaitre","doi":"10.1681/ASN.0000001212","DOIUrl":"https://doi.org/10.1681/ASN.0000001212","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794892","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":"Artificial Intelligence Structural Biology in Nephrology: Powerful Scaffolds, Fragile Certainties.","authors":"Carmine Zoccali, Enrico Petretto, Giovambattista Capasso, Loreto Gesualdo, Francesca Mallamaci, Wisit Cheungpasitporn, Francesco Pesce","doi":"10.1681/ASN.0000001254","DOIUrl":"10.1681/ASN.0000001254","url":null,"abstract":"<p><p>Artificial intelligence (AI)-based protein structure prediction has rapidly entered nephrology, providing plausible atomic models for channels, transporters, receptors, and scaffolds that previously lacked structural information. AlphaFold and RoseTTAFold currently underpin mechanistic interpretations of inherited kidney diseases, including autosomal dominant polycystic kidney disease, cystinosis, and Alport syndrome, and support experimental design in cryo-electron microscopy and cryo-electron tomography. For nephrologists, this means that renal proteins no longer need to be treated as black boxes: Genetic, biochemical, and physiologic data can at present be mapped onto concrete 3-dimensional scaffolds. However, the apparent precision of AI models can be misleading. Renal proteins frequently fall within underrepresented classes, including multipass membrane proteins, intrinsically disordered scaffolds, and human-specific isoforms with shallow multiple sequence alignments, where confidence scores may not accurately reflect model reliability. Current predictors typically deliver static snapshots, whereas transporters, channels, and slit-diaphragm complexes function as dynamic ensembles embedded in specific lipid and macromolecular environments. Attempts to use AlphaFold directly for variant classification or to estimate changes in thermodynamic stability or function show only modest agreement with mutagenesis data, particularly for gain-of-function and dominant-negative alleles that depend on subtle conformational and interaction changes. Common pitfalls include overinterpreting oligomeric stoichiometry inferred from AlphaFold Multimer, reading too much into domain orientations with high predicted aligned error, and dismissing low-confidence regions as modeling failures rather than recognizing intrinsically disordered, potentially regulatory segments. Integrative approaches combining cryo-ET, crosslinking mass spectrometry, and molecular dynamics can mitigate these limitations but remain labor intensive and low throughput. An explainable, hypothesis-driven use of AI that treats predicted structures as working scaffolds to be cross-validated against imaging, biophysics, and functional assays offers the most reliable path toward a genuinely mechanistic nephrology and responsible clinical translation of AI-based structural insights.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794864","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":"Joint Interpretation of Long-Chain and Very Long-Chain Sphingolipid Associations with Mortality in Hemodialysis.","authors":"Zijun Zhou, Bo Yang","doi":"10.1681/ASN.0000001211","DOIUrl":"https://doi.org/10.1681/ASN.0000001211","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794874","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}