Journal of The American Society of Nephrology最新文献

{"title":"Quantum Dot Microsphere-Based Lateral Flow Immunoassay Strip for Rapid Detection of Anti-nephrin Autoantibodies in Idiopathic Nephrotic Syndrome.","authors":"Mingyu Lai, Rui Gu, Jiayi Shen, Tong Shao, Baohua Yang, Jianhua Mao, Qing Ye","doi":"10.1681/ASN.0000001246","DOIUrl":"10.1681/ASN.0000001246","url":null,"abstract":"<p><strong>Key points: </strong>A quantum dot microsphere-based lateral flow immunoassay strip was developed for rapid qualitative detection of anti-nephrin autoantibodies within 10 minutes. The quantum dot microsphere-based lateral flow immunoassay strip demonstrated good analytical performance, with an area under the curve of 0.90, resistance to the tested interferents, and stable detection performance. The quantum dot microsphere-based lateral flow immunoassay strip achieved 92% overall percent agreement with immunoprecipitation-western blotting and identified additional nephrin-specific positive samples not detected by immunoprecipitation-western blotting.</p><p><strong>Background: </strong>Idiopathic nephrotic syndrome is a common primary glomerular disease in children. Circulating anti-nephrin autoantibodies have emerged as clinically relevant biomarkers, but existing detection methods are complex and time consuming. We developed a quantum dot microsphere-based lateral flow immunoassay strip (QD-LFIA) for rapid serum anti-nephrin autoantibody detection.</p><p><strong>Methods: </strong>Quantum dot microspheres were conjugated to recombinant human nephrin protein, and the reading time, test line coating concentration, and nephrin protein labeling amount were optimized. Analytical performance was evaluated by receiver operating characteristic analysis on the basis of test line/control line ratios generated by the dry fluorescence immunoanalyzer, together with interference and accelerated stability testing. Clinical performance was assessed in 191 pediatric serum samples, with qualitative QD-LFIA results compared against immunoprecipitation-western blotting (IP-WB). Discordant samples were evaluated by a recombinant nephrin protein inhibition assay. Clinical indices were compared between anti-nephrin autoantibody-positive and -negative patients.</p><p><strong>Results: </strong>The optimized reaction time, test line coating concentration, and recombinant nephrin protein labeling amount were 10 minutes, 0.5 mg/ml, and 92.4 μ g, respectively. Receiver operating characteristic analysis yielded an area under the curve of 0.90 (95% confidence interval, 0.84 to 0.97), with 93% sensitivity and 92% specificity at a test line/control line cutoff of 0.003. The QD-LFIA resisted the tested interferents and maintained stable performance for 40 days at 37°C. QD-LFIA achieved overall, positive, and negative percent agreements of 92%, 89%, and 93%, respectively, relative to IP-WB. Recombinant nephrin protein inhibition abolished the signals in all 12 QD-LFIA-positive/IP-WB-negative samples. anti-nephrin autoantibody-positive patients had higher 24-hour urinary protein excretion and lower serum albumin levels than negative patients.</p><p><strong>Conclusions: </strong>These findings suggest that the QD-LFIA enabled rapid detection of anti-nephrin autoantibodies in children with idiopathic nephrotic syndrome. The QD-LFIA showed good agreement with IP-WB and ident","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912691","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":"Macrophage IgG Recycling Couples Glomerular IgG Accumulation to Podocyte Senescence in Obesity-Related Glomerulopathy.","authors":"Zikang Liu, Binbin Dai, Yuxuan Jin, Jiwen Bao, Hanxue Zhao, Yurong Lin, Hongtu Hu, Yangbin Pan","doi":"10.1681/ASN.0000001243","DOIUrl":"https://doi.org/10.1681/ASN.0000001243","url":null,"abstract":"<p><strong>Background: </strong>Obesity-related glomerulopathy is increasingly common, yet its pathogenesis remains poorly understood. This study aimed to elucidate the mechanisms by which nonspecific glomerular IgG deposition promotes podocyte senescence in obesity-related glomerulopathy, thereby expanding potential therapeutic options.</p><p><strong>Methods: </strong>Kidney samples from patients with obesity-related glomerulopathy and diet-induced obese mice were used to compare glomerular IgG localization and abundance in obese versus control states. Causality between glomerular IgG accumulation and podocyte senescence was assessed by exogenous IgG supplementation and B cell deficiency mice. Primary podocytes were IgG-stimulated for transcriptomic and lipidomic profiling, and sphingomyelin phosphodiesterase 3 (Smpd3) was validated by in vitro and in vivo loss-of-function studies. Macrophage-specific FcRn deletion and anti-CD20 therapy were further used to evaluate IgG-targeted strategies for mitigating podocyte senescence and injury in ORG.</p><p><strong>Results: </strong>Glomerular IgG deposition was markedly increased in both patients with obesity-related glomerulopathy and mice with diet-induced obesity. Exogenous IgG supplementation in non-obese mice reproduced the glomerular IgG accumulation and podocyte senescence observed in HFD fed mice. Conversely, B-cell null diet-induced obese mice and anti-CD20 treated diet-induced obese mice showed greatly reduced glomerular IgG levels and attenuated podocyte injury. Mechanistically, IgG exposure activated podocyte sphingolipid metabolism, notably upregulating Smpd3 and increasing intra-podocyte ceramide. In vitro and in vivo Smpd3 knockdown prevented IgG induced ceramide accumulation and podocyte senescence. Obesity also heightened glomerular macrophage infiltration, and macrophage depletion or macrophage-specific FcRn knockout significantly reduced glomerular IgG deposition and protected against podocyte injury and senescence.</p><p><strong>Conclusions: </strong>FcRn-expressing macrophages increased obesity-induced IgG retention in glomeruli, which led to podocyte ceramide overload and senescence.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891893","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":"Risk, Not Just Rate: Toward Individualized Correction in Hyponatremia.","authors":"Harish Seethapathy, Sahir Kalim, Sagar U Nigwekar","doi":"10.1681/ASN.0000001270","DOIUrl":"10.1681/ASN.0000001270","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887928","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":"Chimeric HLA Antibody Receptor (CHAR) T Cells to Specifically Eliminate HLA-DQ-Specific B Cells.","authors":"Carolt Arana, Ilse Gille, Renate Hagedoorn, Ainhoa García-Busquets, Hannah C M Schenk, Sergi Betriu, Dennis F G Remst, Ellen M W van der Meer-Prins, Yvonne J H de Vaal, Kim H Voogt-Bakker, Rico Buchli, Aiko P J de Vries, Manel Juan, Cynthia S M Kramer, Eduard Palou, Dave L Roelen, Fritz Diekmann, Mirjam H M Heemskerk, Jordi Rovira, Sebastiaan Heidt","doi":"10.1681/ASN.0000001244","DOIUrl":"https://doi.org/10.1681/ASN.0000001244","url":null,"abstract":"<p><strong>Background: </strong>CAR T cell therapy has revolutionized the treatment of hematological malignancies by effectively eliminating tumor cells. In the field of kidney transplantation, comparable cellular therapies are being explored to facilitate transplantation and prevent graft rejection. Chimeric HLA antibody receptor (CHAR) T cells are a promising therapy for eliminating HLA-specific B cells in sensitized patients and potentially ameliorating antibody-mediated rejection. We previously demonstrated that HLA class I CHAR T cells selectively eliminated HLA class I-specific B cells with high specificity. Since HLA sensitization is most often directed against HLA-DQ of the allograft, we developed HLA-DQ2 and HLA-DQ7 CHAR T cells to target B cells with corresponding HLA specificity.</p><p><strong>Methods: </strong>We designed viral vectors encoding HLA-DQ CHARs composed of HLA-DQA1*05:01 alpha chain with either HLA-DQB1*02:01 (HLA-DQ2) or HLA-DQB1*03:01 (HLA-DQ7) beta chains, CLIP peptide, and intracellular 4-1BB costimulatory and CD3ζ signaling domains. Upon production of HLA-DQ CHAR T cells, we evaluated CHAR expression, cytotoxic activity, production of cytokines and cytotoxic mediators, and sensitivity to immunosuppressive drugs in in vitro models. We further assessed the cytotoxic activity of HLA-DQ CHAR T cells in an immunodeficient mouse model and in primary material from sensitized individuals.</p><p><strong>Results: </strong>CHAR-transduced Jurkat Triple Parameter Reporter (JurkatTPR) cells expressing reporter constructs for T cell activation markers showed robust activation upon specific stimulation. Primary CD8+ T cells expressing HLA-DQ2 and HLA-DQ7 CHAR molecules specifically eliminated HLA-DQ2- or HLA-DQ7-specific B cells, respectively, and produced interferon gamma, soluble Fas ligand, perforin, and granzyme B. Maintenance immunosuppressive drug regimens initiated at the time of co-incubation with target cells had limited effects on CHAR T-cell functionality. Finally, HLA-DQ CHAR T cells effectively eliminated HLA-DQ-specific B cells in an in vivo mouse model, as well as in primary material from sensitized individuals.</p><p><strong>Conclusions: </strong>HLA-DQ2 and HLA-DQ7 CHAR T cells, the first HLA class II CHAR T cells, selectively and effectively eliminated corresponding HLA-DQ-specific B cells in vitro, in vivo, and in primary material from sensitized individuals.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887899","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":"Impaired BCAA Catabolism Drives Peritoneal Fibrosis via BCKA-Mediated Suppression of the Pentose Phosphate Pathway.","authors":"Jiayang Li, Tiangang Wu, Junhao Dai, Xin Zhao, Svetlana Reilly, Xin Liu, Dongliang Zhang, Hong Xin, Nan Zhu, Zhiping Li, Zanzhe Yu, Xuemei Zhang","doi":"10.1681/ASN.0000001241","DOIUrl":"https://doi.org/10.1681/ASN.0000001241","url":null,"abstract":"<p><strong>Background: </strong>Peritoneal dialysis (PD) is a life-sustaining therapy for kidney failure, yet its long-term viability is compromised by progressive peritoneal fibrosis in some patients. Currently, reliable treatment options are lacking as the pathogenesis remains poorly understood, with the metabolic underpinnings of fibrotic progression remaining particularly elusive.</p><p><strong>Methods: </strong>Using a physiologically relevant framework comprising human primary mesothelial cells and a PD fluid-exposed mouse model, we performed bidirectional genetic and pharmacological modulation of branched-chain amino acid catabolism. Integrated proteomic and metabolomic analyses were conducted to investigate downstream metabolic consequences.</p><p><strong>Results: </strong>We identified profound impairment in branched-chain amino acid (BCAA) catabolism, centered on a functional bottleneck at the rate-limiting branched-chain α-ketoacid dehydrogenase complex, as a metabolic hallmark of peritoneal fibrosis. Functional uncoupling of the amino acids from their ketoacid derivatives indicated that branched-chain α-ketoacid (BCKA) burden was more closely linked to the fibrotic phenotype than BCAA abundance alone. Mechanistically, BCKA burden was associated with reduced glucose-6-phosphate dehydrogenase expression and activity, lower NADPH-generating capacity, and increased intracellular oxidant burden.</p><p><strong>Conclusions: </strong>Together, these findings showed that BCKA burden, rather than BCAA abundance alone, more closely tracked fibrotic responses and was linked to reduced pentose phosphate pathway-associated redox capacity in peritoneal fibrosis.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874409","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":"Recurrent Antibiotic-Treated Pyelonephritis Depletes Renal Functional Reserve Despite Preserved Basal GFR in a Reflux-Prone Mouse Model.","authors":"Evan A Rajadhyaksha, Samuel Arregui, Vijay Saxena, Alleé Shaw, Jennifer L Anderson, Sayeh Gholampoor, Gokul Achayaraj, Rose Odom, Danielle E Soranno, David S Hains, Andrew L Schwaderer","doi":"10.1681/ASN.0000001166","DOIUrl":"10.1681/ASN.0000001166","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"2027-2029"},"PeriodicalIF":9.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13567891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148176135","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":"Clarifying Crossover Interpretation and Volume-Signal Assessment in ASSIST.","authors":"Dongmei Cheng, Lin Zhan, Huan Zhou","doi":"10.1681/ASN.0000001141","DOIUrl":"10.1681/ASN.0000001141","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"2079-2080"},"PeriodicalIF":9.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13567889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148205224","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":"Correction to: HSP72 Inhibits Smad3 Activation and Nuclear Translocation in Renal Epithelial-to-Mesenchymal Transition.","authors":"Yi Zhou, Haiping Mao, Shu Li, Shirong Cao, Zhijian Li, Shougang Zhuang, Jinjin Fan, Xiuqing Dong, Steven C Borkan, Yihan Wang, Xueqing Yu","doi":"10.1681/ASN.0000001114","DOIUrl":"10.1681/ASN.0000001114","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"2082-2084"},"PeriodicalIF":9.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13567896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147616277","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":"Alport: Renaming an Extended Clinical Spectrum.","authors":"Rachel Lennon, Jeffrey H Miner, Judy Savige, B André Weinstock, Susie Gear","doi":"10.1681/ASN.0000001106","DOIUrl":"10.1681/ASN.0000001106","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"2062-2064"},"PeriodicalIF":9.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13567868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513159","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":"Tenascin C-Derived Peptide 6 Promotes De Novo Kidney Regeneration after Partial Nephrectomy in Axolotl.","authors":"Jianqing Liang, Liting Chen, Liuyan Xiao, Shihui Lin, Leilei Zhao, Xue Hong, Fan Fan Hou, Fujian Zhang, Youhua Liu","doi":"10.1681/ASN.0000001066","DOIUrl":"10.1681/ASN.0000001066","url":null,"abstract":"<p><strong>Key points: </strong>De novo nephron regeneration was achieved after partial nephrectomy in axolotls. Tenascin C induction peaked at 2-4 weeks postpartial nephrectomy and coincided with cell proliferation and extracellular matrix remodeling. Tenascin C-derived peptide 6, a tenascin C-derived matrikine, accelerated kidney regeneration by enhancing extracellular matrix remodeling and tenascin C expression.</p><p><strong>Background: </strong>Kidneys possess limited regenerative capacity. While renal tubules are capable of repair after injury, nephron loss resulting from renal mass ablation or disease is irreversible in mammals. In this study, we demonstrated de novo nephron regeneration after partial nephrectomy in axolotls, a model organism renowned for its remarkable regenerative ability.</p><p><strong>Methods: </strong>Kidney mass ablation was performed by using unilateral one-quarter partial nephrectomy in axolotls, and the regeneration process was assessed at multiple time points (0, 1, 2, 4, 8, 12, and 16 weeks) postsurgery.</p><p><strong>Results: </strong>We found that cells migrated into the wound sites and proliferated, beginning at 1 week postnephrectomy and nearly restoring the cell mass of the contralateral kidney by 4 weeks. Cell proliferation peaked between weeks 2 and 4 at the resected site and was accompanied by fibroblast activation, SOX9 expression, and induction of tenascin C. By 16 weeks after nephrectomy, new glomeruli had formed and renal tubules were de novo regenerated and functionally matured. Notably, tenascin C expression was transiently induced, peaking at 2-4 weeks postsurgery and rapidly declined as cell repopulation progressed. Knockdown of tenascin C expression reduced cell proliferation and impaired regenerative process. Conversely, administration of tenascin C-derived peptide 6 shifted tenascin C expression to an earlier stage and accelerated both new nephron formation and functional maturation.</p><p><strong>Conclusions: </strong>These studies demonstrate de novo nephron regeneration after partial nephrectomy in an animal model and identify tenascin C-derived peptide 6 as an accelerator of kidney regeneration in vivo .</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1936-1953"},"PeriodicalIF":9.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13567864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147616247","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}