Journal of The American Society of Nephrology最新文献

{"title":"Authors' Reply: Using Alzheimer's Disease Cerebrospinal Fluid Biomarkers in CKD: A Caution for Clinicians.","authors":"Yuwei Lin, Sara Garcia Ptacek, Maria Eriksdotter, Hong Xu","doi":"10.1681/ASN.0000001257","DOIUrl":"https://doi.org/10.1681/ASN.0000001257","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167119","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":"Kidney Tubule Aging Across Adulthood.","authors":"Merve Postalcioglu, Ronit Katz, Mark J Sarnak, Orlando M Gutierrez, David R Jacobs, Ankeet S Bhatt, Cora E Lewis, Joachim H Ix, Michael G Shlipak","doi":"10.1681/ASN.0000001284","DOIUrl":"https://doi.org/10.1681/ASN.0000001284","url":null,"abstract":"<p><strong>Background: </strong>Aging is associated with declining kidney health as defined by lower eGFR and higher albuminuria. Age-related changes in kidney tubule health have not been well studied.</p><p><strong>Methods: </strong>We analyzed a subset of participants from 2 cohorts, the Coronary Artery Risk Development in Young Adults (CARDIA) Year 20 (n=939) and the Multi-Ethnic Study of Atherosclerosis (MESA) Exam 1 (n=1,014); 780 and 668, respectively, who completed 10-year follow-up. Seven urine biomarkers were measured reflecting tubular synthetic function (EGF and UMOD), tubule reabsorption function (α1m), proximal tubular injury (IL-18 and KIM-1), and interstitial fibrosis/repair (MCP-1 and YKL-40), and were compared with albuminuria and eGFR. In pooled data, cross-sectional analyses evaluated age associations across the range of 37-84 years, and longitudinal analyses were performed to quantify changes over 10-years of follow-up.</p><p><strong>Results: </strong>Age ranges were 37-55 and 45-84 years for CARDIA and MESA at baseline, respectively; mean eGFR was 96±15 and 78±16 ml/min/1.73m2, and median urine albumin-to-creatinine ratios (UACR) were 4.5 [IQR: 3.3, 1.2] and 5.2 [3.3, 11] mg/g. In multivariable cross-sectional analyses, older age (per decade) was associated with higher urine α1m/UCr (23%, 95% CI: 17, 28%), IL-18/UCr (5%: 0.4, 9%), KIM-1/UCr (16%:12, 20%), MCP-1/UCr (20%: 16, 23%), YKL-40/UCr (12%: 5, 20%), UACR (30%: 23, 38%), and lower urine EGF/UCr (-13%: -15, -11%) and eGFR (-9%; -10, -8%). Age at baseline was not significantly associated with urine UMOD/UCr. In longitudinal analyses over 10-years of follow up, EGF/UCr (-20%: 95% CI: -22, -19%) and UMOD/UCr (-22%: -25, -18%) decreased and α1m/UCr (30%: 24, 35%), MCP-1/UCr (9%: 6, 13%), and YKL-40/UCr (29%: 20, 39%) increased; additionally, albuminuria increased by 29% (23, 36%) and eGFR decreased by 10% (9, 10.4%).</p><p><strong>Conclusions: </strong>In community-based adults aged 37-84 years, aging was associated with worsening tubular function and injury.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167936","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: IHG-1 Promotes Mitochondrial Biogenesis by Stabilizing PGC-1α.","authors":"Fionnuala B Hickey, James B Corcoran, Neil G Docherty, Brenda Griffin, Una Bhreathnach, Fiona Furlong, Finian Martin, Catherine Godson, Madeline Murphy","doi":"10.1681/ASN.0000001302","DOIUrl":"https://doi.org/10.1681/ASN.0000001302","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170058","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: β-Blockers in Hemodialysis Outcome Trial.","authors":"Ali Etemadi, Wolfgang C Winkelmayer, Maria E Montez-Rath, Tara I Chang","doi":"10.1681/ASN.0000001265","DOIUrl":"https://doi.org/10.1681/ASN.0000001265","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166483","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":"A Microsimulation of Eligibility for Cardiorenal Combination Treatment and Potential Deaths Averted.","authors":"Massimo Nardone, Labib Faruque, Lisa Dubrofsky, Mai Mohsen, Matthew Cooper, Tyler D Brown, Ann Young, Bourne L Auguste, Husam Abdel-Qadir, Ron Wald, Frederik Persson, Ian H de Boer, Christoph Wanner, Javed Butler, Peter Juni, Nikolaus Marx, David Z I Cherney, Tiago V Pereira, Ayodele Odutayo","doi":"10.1681/ASN.0000001287","DOIUrl":"https://doi.org/10.1681/ASN.0000001287","url":null,"abstract":"<p><strong>Background: </strong>Clinical guidelines recommend combined use of renin-angiotensin system inhibitors (RASi), sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP1RA) and nonsteroidal mineralocorticoid receptor antagonists (nsMRA) to reduce cardiorenal risk. However, eligibility for combination treatment and the potential effects of implementation on preventing mortality remain unclear.</p><p><strong>Methods: </strong>We conducted a microsimulation study using data from the National Health and Nutrition Examination Survey (NHANES 2007-2016 and 2017-2020). The model incorporated acute treatment effects of RASi, SGLT2i, GLP1RA, and nsMRA on estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), and serum potassium. Eligibility for combination treatment was assessed for each participant according to 73 clinical practice guideline recommendations and inclusion criteria from recently published clinical trials. Primary outcomes included: 1) the percentage of participants eligible for single or combination treatment with RASi, SGLT2i, GLP1RA, and nsMRA, and 2) the projected potential number of annually averted all-cause and cardiovascular deaths.</p><p><strong>Results: </strong>Of 8,152 adults, 15% had type 2 diabetes (DM), 14% had chronic kidney disease (CKD) and 5% had DM and CKD (DKD). Among all U.S. adults, 19% were treated with RASi, 1% with SGLT2i, 1% with GLP1RA and none with nsMRA. The dual-therapy associated with the highest eligibility was RASi+SGLT2i, with 15% of the U.S. population eligible (DM subgroup: 70%; CKD subgroup: 50%; DKD subgroup: 84%). The triple-therapy with the highest eligibility was RASi+SGLT2i+GLP1RA, with 11% overall eligibility (DM: 69%; CKD: 33%; DKD: 83%). Eligibility for quadruple-therapy was 4% overall (DM: 22%; CKD: 17%; DKD: 40%). Based on our microsimulation model, fewer individuals with diabetes were eligible for triple-therapy with RASi+SGLT2i+GLP1RA compared to dual-therapy with RASi+SGLT2i, but triple-therapy was projected to prevent 2-fold more potential all-cause and cardiovascular deaths versus dual-therapy.</p><p><strong>Conclusions: </strong>Under the assumptions of our microsimulation model, eligibility for combined treatment with cardiorenal protective therapies was prevalent, particularly in adults with type 2 diabetes and/or CKD.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149116","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":"Epithelial PDGF-C Contributes to Crescentic Glomerulonephritis and FSGS in Part via Activation of Parietal Epithelial Cells.","authors":"Ina V Martin, Yingying Gao, Dickson W L Wong, Roman D Bülow, Mirna Barsoum, Lisa Nguyen, Rachel P L van Swelm, Peter Boor, Ulf Eriksson, Maja T Lindenmeyer, Clemens D Cohen, Ulf Panzer, Christian F Krebs, Rafael Kramann, Jürgen Floege, Ute Raffetseder, Bart Smeets, Gerald S Braun, Eleni Stamellou, Tammo Ostendorf","doi":"10.1681/ASN.0000001274","DOIUrl":"https://doi.org/10.1681/ASN.0000001274","url":null,"abstract":"<p><strong>Background: </strong>Activated parietal epithelial cells (PECs) and podocytes are key effector cells in the development of crescentic glomerulonephritis and focal segmental glomerulosclerosis (FSGS). Platelet-derived growth factor (PDGF)-C has been found to be important for tubulointerstitial fibrosis development, but its relevance for crescentic glomerulonephritis and FSGS was previously unknown.</p><p><strong>Methods: </strong>To address this, expression analyses for both PDGF-C and its receptor PDGFRα were carried out in mouse and human kidney tissues. To further elucidate a functional role of PDGF-C, the murine nephrotoxic nephritis model of crescentic glomerulonephritis was induced in a) Pdgfc-deficient mice, b) mice treated with a neutralizing PDGF-C antibody, and c) Pax8-cre::Pdgfcfl/fl mice with conditional Pdgfc deletion in kidney epithelial cells. We also subjected the collapsing FSGS model of the anti-Thy1.1 transgenic mouse to pharmacological PDGF-C inhibition. The studies were supplemented by PEC in vitro analyses.</p><p><strong>Results: </strong>Our data showed that PDGF-C was upregulated in PECs and expressed de novo in podocytes under disease conditions. It promoted the proliferation and activation of primary as well as conditionally immortalized PECs in vitro. In both the genetic and pharmacological PDGF-C intervention studies in murine crescentic glomerulonephritis and FSGS, significant improvements in glomerular crescent formation, glomerular sclerosis, renal inflammation and kidney function parameters were observed upon PDGF-C deficiency or antagonism. Mechanistically, transcription factor FOXM1 was identified as a mediator of disease-related PDGF-C expression in PECs.</p><p><strong>Conclusions: </strong>Our studies identified epithelial PDGF-C as a contributor to disease progression in crescentic glomerulonephritis and FSGS, acting in part through the activation of parietal epithelial cells.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148866","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":"Fibroblastic Reticular Cell-Derived and CD5L-Enriched Exosomes Remodel Renal Lipid Metabolism in Porcine Sepsis-Associated Acute Kidney Injury.","authors":"Yiming Li, Wen Wu, Dongxue Xu, Pan Zhai, Chang Hu, Jinmeng Suo, Yusheng Chen, Xiaoyu Zhang, Xiang Zhou, Xiaocheng Weng, Timothy R Billiar, John A Kellum, Jing Wang, Bo Hu, Zhiyong Peng","doi":"10.1681/ASN.0000001266","DOIUrl":"https://doi.org/10.1681/ASN.0000001266","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-associated AKI is a life-threatening condition associated with profound metabolic dysfunction, including impaired mitochondrial fatty acid handling. Therapies capable of reversing this metabolic dysfunction remain lacking. Using a clinically relevant porcine model, we investigated whether kidney-targeted fibroblastic reticular cell-derived and CD5L-enriched exosomes could ameliorate sepsis-associated AKI.</p><p><strong>Methods: </strong>We generated engineered exosomes derived from fibroblastic reticular cells or CD5L-overexpressing cells and functionalized them with the kidney-targeting LTH peptide. Therapeutic efficacy and safety were evaluated in a porcine model of lipopolysaccharide-induced sepsis-associated AKI. Integrated multiomic and cellular analyses were performed to examine the associated molecular pathways.</p><p><strong>Results: </strong>In septic pigs, both fibroblastic reticular cell-derived and CD5L-enriched exosomes improved systemic hemodynamics, renal microvascular perfusion, and kidney injury indices. Exosome treatment reduced renal lipid-droplet and acylcarnitine accumulation. CD5L interacted with fatty acid synthase, and treatment was associated with changes in short-chain fatty acids and AMPK-ACC-CPT1A signaling. These lipid-metabolic changes were accompanied by improved mitochondrial bioenergetic indices, preserved mitochondrial morphology, and reduced markers of tubular cell pyroptosis.</p><p><strong>Conclusions: </strong>Kidney-targeted fibroblastic reticular cell-derived and CD5L-enriched exosomes produced comparable improvements in kidney injury indices and were associated with renal lipid-metabolic and mitochondrial remodeling in a large-animal model of sepsis-associated AKI.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137430","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":"Modifiers of Severity of Kidney Injury in Apolipoprotein L1 Nephropathy","authors":"Antonio S. Novaes,Ubong S. Ekperikpe,Ilse S. Daehn","doi":"10.1681/asn.0000001276","DOIUrl":"https://doi.org/10.1681/asn.0000001276","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"1 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088823","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":"Comparative Cardiovascular Outcomes of Lanthanum Carbonate and Sevelamer in Dialysis","authors":"Jiao Liu,Luhua Jin,Fan Luo,Shiyu Zhou,Caoxiang She,Ruwen Fang,Yuping Zhang,Xin Xu,Sheng Nie","doi":"10.1681/asn.0000001289","DOIUrl":"https://doi.org/10.1681/asn.0000001289","url":null,"abstract":"Background: Hyperphosphatemia is a key component of chronic kidney disease–mineral and bone disorder and is associated with cardiovascular morbidity and mortality in patients receiving dialysis. Non–calcium-based phosphate binders, including sevelamer and lanthanum carbonate, are widely used, yet comparative evidence on clinical outcomes remains limited. Methods: We emulated a target trial using data from the China Renal Data System to compare lanthanum carbonate versus sevelamer initiation among patients receiving dialysis with hyperphosphatemia and no documented prior major adverse cardiovascular events (MACE). Using an active-comparator, new-user design, patients were matched 1:1 by propensity scores. The primary outcome was incident MACE, defined as a composite of myocardial infarction, stroke, or cardiovascular death. Secondary outcomes included all-cause and cardiovascular mortality. Cox proportional hazards models were used to estimate hazard ratios (HRs), and cumulative incidence was estimated using the Kaplan–Meier method. Results: Among 10,518 matched patients (5,259 per group), 325 MACE events occurred in the sevelamer group and 280 in the lanthanum carbonate group over 3 years. The cumulative incidence of MACE was 12.2% versus 9.5%, respectively. Lanthanum carbonate initiation was associated with a lower risk of MACE (HR, 0.79; 95% CI, 0.68 to 0.92), corresponding to an absolute risk reduction of 2.68% and a number needed to treat of 37. Lanthanum carbonate was also associated with lower risks of all-cause mortality (HR, 0.83; 95% CI, 0.75 to 0.93) and cardiovascular mortality (HR, 0.72; 95% CI, 0.59 to 0.88). Results were consistent across sensitivity and subgroup analyses. In competing-risk analyses, the association with lower MACE risk remained significant. Conclusions: In this target trial emulation, initiation of lanthanum carbonate was associated with lower risks of cardiovascular events and mortality compared with sevelamer among patients receiving dialysis with hyperphosphatemia and no documented prior MACE.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"20 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088824","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: Normalization Benchmarking for nCounter Diagnostics Requires Deployment- and Biology-Aware Evaluation.","authors":"Alexis Piedrafita, Marta Sablik, Alexandre Loupy","doi":"10.1681/ASN.0000001234","DOIUrl":"10.1681/ASN.0000001234","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"2348-2349"},"PeriodicalIF":9.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813348","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}