Journal of The American Society of Nephrology最新文献

{"title":"Association of Complement Factor D with Cardiovascular Mortality and Clot Lysis in CKD.","authors":"Martin Berger,Martin Reugels,Alexandra Heinzmann,Katharina Lysaja,Marta Rizk,Jaana-Sophia Kern,Michael Wolf,Stefan Wolfart,Vera Jankowski,Joachim Jankowski,Nikolaus Marx,Katharina Marx-Schütt","doi":"10.1681/asn.0000000870","DOIUrl":"https://doi.org/10.1681/asn.0000000870","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"66 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930173","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":"Differential Cell-Specific, Regulatory Roles of FcγRIIB through IgG in IgA Nephropathy.","authors":"Tzu-Yu Liu,Chia-Chao Wu,Xiaorui Chen,Chih-Chien Sung,Yu-Ling Chou,Feng-Cheng Liu,Dimitra Lamprinaki,Shun-Min Yang,Chih-Ying Wu,Yu-Ling Tsai,Wei-Ting Wong,Norihito Kawasaki,Kuo-Feng Hua,Cheng-Hsu Chen,Ann Chen,Shuk-Man Ka","doi":"10.1681/asn.0000000835","DOIUrl":"https://doi.org/10.1681/asn.0000000835","url":null,"abstract":"BACKGROUNDIgA nephropathy is the most common form of glomerulonephritis and a leading cause of kidney failure. Ample evidence confirms the deposition of IgA and IgG, as well as the infiltration of mononuclear leukocytes in kidney biopsy specimens from IgA nephropathy patients. Previously, we established an experimental IgA nephropathy model in B cell-deficient mice, implicating interactions between Fcγ receptors (FcγRs) in the pathogenesis of IgA nephropathy. It is generally accepted that FcγRIIB plays a regulatory role in humoral responses; we proposed that FcγRIIB might exert differential kidney-protective effects depending on cell-type specificity, thereby influencing the progression and severity of IgA nephropathy.METHODSUtilizing a mouse model of IgA nephropathy and three different cell types of FcγRIIB-deficient mice, including CEBP/α Cre (myeloid cells), CD11c Cre (dendritic cells) and CD19 Cre (B cells) in floxed FcγRIIB mice, as well as several specific cell models.RESULTSIn the present study, we observed a large increase in albuminuria, kidney function impairment, and kidney injury in FcγRIIB knockout mice with induced IgA nephropathy. We demonstrated that macrophage- and dendritic cell-specific FcγRIIB deficiency enhanced the activation of NLRP3 inflammasome and accelerated the development and severity of IgA nephropathy, whereas this effect was not observed in mice with B cell-specific FcγRIIB deficiency. Moreover, activation of the inflammasome was induced by IgA immune complexes dependent on TLR4/MyD88 signaling, potentially associated with crosstalk between Dectin-2.CONCLUSIONSWe found that FcγRIIB deficiency in macrophages and dendritic cells led to increased albuminuria, kidney dysfunction, and kidney injury in a mouse model of IgA nephropathy. FcγRIIB deficiency enhanced activation of NLRP3 inflammasome through IgA immune complexes in a TLR4/MyD88-dependent manner.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"11 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930176","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":"Enhanced Expression of the Female-Biased Gene Gsta2 in Male Proximal Tubule Cells Improves Renal Resilience to Ischemia-Reperfusion Injury.","authors":"Shun-Yang Cheng,Jinjin Guo,Taylor L Simonian,Paolo Caldarelli,Andrew P McMahon","doi":"10.1681/asn.0000000840","DOIUrl":"https://doi.org/10.1681/asn.0000000840","url":null,"abstract":"BACKGROUNDGenetic sex is an important determinant of kidney injury and repair, with female kidneys typically exhibiting greater resilience to acute kidney injury (AKI). Among the sexually dimorphic genes in mouse proximal tubule cells, Gsta2, encoding an NRF2-regulated antioxidant enzyme, is strongly enriched in females. Here, we hypothesized that augmenting Gsta2 expression in male proximal tubule cells will enhance resistance to ischemia-reperfusion injury (IRI).METHODSTo enable proximal tubule cell-specific expression of transgenes, we mapped and verified enhancer regions directing proximal tubule expression of human HNF4A. A synthetic HNF4A enhancer cassette driving Gsta2 was introduced into a safe harbor locus in transgenic mice thereby enhancing expression of Gsta2 in male mice. Following unilateral nephrectomy, transgenic and wild-type males were subjected to IRI. Post-IRI outcomes were assessed by examining kidney function, histological injury, and fibrotic progression for up to 28 days post-injury.RESULTSEnhancing Gsta2 expression in male proximal tubule cells lead to significantly higher glomerular filtration rates and attenuated fibrotic remodeling following IRI. Early-phase transcriptional analyses 4-hours post-injury showed reduced expression of immediate early genes (Jun, Fos, Egr1) suggesting a reduced stress response, diminished DNA double-strand DNA breaks (γH2AX incorporation into chomatin), and lower protein peroxidation. Later stage transgenic kidneys exhibited a reduction in fibrosis-associated transcripts (Acta2, Col1a1, Col3a1) and markers of failed proximal tubule cells repair (Havcr1, Vcam1, Ccl2).CONCLUSIONSEctopic expression of Gsta2 in male proximal tubule cells reduced oxidative injury, injury associated fibrosis and maladaptive stress signaling following ischemia reperfusion injury.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"16 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930178","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":"The KLF6-RPB1 Pathway: Setting the Transcriptional Stage for Failed Tubular Recovery.","authors":"Volker Vallon","doi":"10.1681/asn.0000000836","DOIUrl":"https://doi.org/10.1681/asn.0000000836","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"116 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930177","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":"Calciprotein Particles and the Mineral Buffering System of Blood: Preventing the Toxicity of Mineral Stress.","authors":"Daniel Cejka, Mathias Haarhaus, Andreas Pasch, Edward R Smith","doi":"10.1681/ASN.0000000863","DOIUrl":"https://doi.org/10.1681/ASN.0000000863","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054133","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":"Trends in Steroidal Mineralocorticoid Receptor Antagonist Prescriptions by Nephrologists after Approval of the Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone for CKD.","authors":"Daniel Edmonston, Benjamin Catanese, Matthew Sparks","doi":"10.1681/ASN.0000000854","DOIUrl":"10.1681/ASN.0000000854","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873732","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":"Beyond Hyperfiltration: Comprehensive Morphometric Assessment of Nephrons and Podocytes.","authors":"Kotaro Haruhara,John F Bertram,Nobuo Tsuboi","doi":"10.1681/asn.0000000852","DOIUrl":"https://doi.org/10.1681/asn.0000000852","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"146 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144850850","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":"Circulating Mycobiota Signatures and Cardiovascular Mortality among Patients Undergoing Hemodialysis.","authors":"Keiichi Sumida,Yamini Mallisetty,Chi-Yang Chiu,Zhongji Han,Tahliyah S Mims,Cheng Chen,Robert Tyson Beach,Levente Dojcsak,Maki Sumida,Qi Zhao,Amandeep Bajwa,Brian M Peters,Jesse C Seegmiller,Amy B Karger,Peter Stenvinkel,Susmita Datta,Michael A Langston,Csaba P Kovesdy,Joseph F Pierre","doi":"10.1681/asn.0000000829","DOIUrl":"https://doi.org/10.1681/asn.0000000829","url":null,"abstract":"BACKGROUNDAlterations of the circulating microbiota have recently been implicated in the pathogenesis of cardiometabolic disease. However, the evidence is based primarily on bacterial DNA signatures, while the characteristics and roles of circulating fungal DNA signatures (mycobiota) remain unknown.METHODSIn a nationwide prospective cohort of 960 hemodialysis patients, we characterized circulating cell-free mycobiota signatures in baseline serum samples using internal transcribed spacer (ITS) ribosomal DNA (rDNA) sequencing and examined their associations with all-cause and cardiovascular mortality using Cox models with adjustment for potential confounders. The added predictive ability of circulating mycobiota signatures over known risk factors for premature mortality and the mediation effect of inflammation on their association with mortality were also examined.RESULTSIn this cohort, the mean patient age was 60±13 years, 53% of patients were male, 57% had diabetes mellitus, and the median (interquartile interval [IQI]) hemodialysis vintage was 3.1 (1.5, 5.8) years. After stringent quality controls, ITS rDNA was detected in 80% of these patients. Taxonomic analysis of the detected rDNA demonstrated a total of 397 fungal taxa, including 7 phyla, 149 families, and 241 genera. During a median (IQI) follow-up of 2.2 (1.7, 2.4) years, 205 and 75 patients experienced all-cause and cardiovascular death, respectively. While circulating mycobiota signatures were not associated with all-cause mortality, higher α diversity (adjusted HR [95% CI], 1.64 [1.14-2.39] per 1 unit higher) and the presence of specific genera (3.79 [2.20, 6.51], 2.72 [1.44, 5.12], and 2.21 [1.28, 3.81] for Wallemia, Cladosporium, and Fusarium, respectively) were significantly associated with higher cardiovascular mortality, without a significant mediation effect of inflammation. Adding these genera to models with known risk factors improved cardiovascular mortality prediction.CONCLUSIONSCirculating mycobiota signatures were associated with cardiovascular mortality in hemodialysis patients, highlighting their potential as prognostic biomarkers and warranting further mechanistic investigation.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"27 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819806","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":"Dysregulated Bone Marrow Contributes to Glomerular Injury through Soluble Factors.","authors":"Ryan Spear,Alexis P Jimenez-Uribe,Yanxia Cao,Steve Mangos,Ariana G Alcantar,Bong-Hyun Kim,Flavio Vincenti,Jochen Reiser,Eunsil Hahm","doi":"10.1681/asn.0000000828","DOIUrl":"https://doi.org/10.1681/asn.0000000828","url":null,"abstract":"BACKGROUNDImmune dysregulation and chronic inflammation have been implicated in the pathogenesis of CKD. Altered bone marrow hematopoiesis is commonly observed in CKD-associated conditions, such as diabetes, cardiovascular disease, and aging. However, the role of bone marrow dysfunction in CKD progression has not been thoroughly interrogated in humans. This study examines how inflammation-induced bone marrow alterations contribute to CKD progression.METHODSBone marrow aspirates were obtained from 10 CKD patients (8 with FSGS, 6 of whom were kidney transplant recipients) and from healthy donors. Samples were analyzed using ELISA, multiplex cytokine assays, multicolor flow cytometry, and scRNA sequencing. To mimic CKD patient bone marrow alterations, in vitro myelopoiesis assays were conducted under TNFα exposure. Cellular and molecular changes were assessed via ATAC-seq, RNA-seq, metabolic assays, flow cytometry, and cytokine analysis. We tested the in vivo effect of TNFα blockade and co-injection of TNFα with IFNγ in mice. We also measured TNFα levels in three different mouse models of proteinuria and in suPAR-deficient mice. The impact of secreted factors from TNFα-driven, functionally altered myeloid cells on kidney function was evaluated using high-throughput immunofluorescence assays on cultured podocytes and filtration function assays in zebrafish.RESULTSBone marrow from CKD patients exhibited elevated TNFα and suPAR levels, along with inflammatory transcriptomic profiles in monocytic cells. TNFα-driven myelopoiesis in vitro induced altered monocytic cells resembling those in CKD patients. These cells displayed increased metabolic activity, transcriptional and epigenetic reprogramming, and elevated secretion of proinflammatory cytokines and suPAR. In a cooperative manner, these secreted factors caused filtration dysfunction in zebrafish and led to cytoskeletal disarrangement in cultured podocytes. In mice, TNFα exposure during myelopoiesis resulted in increased suPAR levels and proteinuria.CONCLUSIONSTNFα-driven alterations in bone marrow monocytic cells contribute to glomerular dysfunction in CKD, suggesting bone marrow dysfunction as a central upstream driver of CKD.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"33 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144802597","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":"Glutathione Synthesis via the Cystine/Glutamate Transporter Promotes the Formation of Tertiary Lymphoid Structures in the Kidney.","authors":"Hiroyuki Arai,Yuki Sugiura,Shinya Yamamoto,Takahisa Yoshikawa,Yuta Matsuoka,Rae Maeda,Hiroyuki Neyama,Ryo Kamimatsuse,Shima Goto,Keisuke Taniguchi,Naoya Toriu,Makiko Kondo,Yuki Sato,Shingo Fukuma,Motoko Yanagita","doi":"10.1681/asn.0000000825","DOIUrl":"https://doi.org/10.1681/asn.0000000825","url":null,"abstract":"BACKGROUNDTertiary lymphoid structure, an ectopic lymphoid tissue induced under chronic inflammation, develops in various kidney diseases and is associated with poor prognosis. The immune system requires metabolic resources to support immune function and lymphocyte proliferation. Hence, dramatic metabolic alterations presumably occur during the formation of tertiary lymphoid structure. However, it remains unclear whether metabolic remodeling occurs during this formation and its underlying mechanism.METHODSIn a murine model of renal tertiary lymphoid structures, we used imaging mass spectrometry and metabolome analysis to investigate the metabolic pathway that characterizes tertiary lymphoid structures. We also performed in situ hybridization with immunofluorescence and pharmacological inhibition to explore the expression and function of the key molecules governing the pivotal metabolic pathway. We analyzed urine samples from mice and humans to explore the metabolites estimating the presence of renal tertiary lymphoid structures.RESULTSSignificant glutathione accumulation and depletion of cysteine, which is essential for glutathione synthesis, was observed specifically within tertiary lymphoid structures. The kidneys with tertiary lymphoid structures exhibited higher glutathione concentrations than healthy kidneys. Tertiary lymphoid structures also showed significant accumulation of 4-HNE and 8-OHdG, markers of oxidative stress. Dendritic cells and fibroblasts within tertiary lymphoid structures expressed the cystine/glutamate transporter, that regulates glutathione synthesis, and supplied synthesized glutathione to lymphocytes, which lacked its expression. Pharmacological inhibition of the cystine/glutamate transporter prevented tertiary lymphoid structure formation in the kidney. Furthermore, enhanced glutathione synthesis within tertiary lymphoid structures was reflected in elevated urinary glutathione concentrations both in mice and humans, which effectively detected the presence of tertiary lymphoid structures in the kidney in IgA nephropathy patients.CONCLUSIONSGlutathione significantly accumulated within tertiary lymphoid structures in the kidney. Inhibition of the cystine/glutamate transporter prevented the formation of tertiary lymphoid structures. Urinary glutathione served as a biomarker to detect tertiary lymphoid structures in the kidney.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"699 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144802511","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}