Kidney international最新文献

{"title":"The metabolite alpha-ketoglutarate inhibits vascular calcification partially through modulation of TET2/NLRP3 inflammasome signaling pathway.","authors":"Mingwei Fu,Zirong Lan,Yuanzhi Ye,Yuan Gong,Qingchun Liang,Mingxi Li,Liyun Feng,An Chen,Qianqian Dong,Yining Li,Siyi Wang,Xiaoyu Liu,Xiuli Zhang,Jing-Song Ou,Lihe Lu,Jianyun Yan","doi":"10.1016/j.kint.2025.04.016","DOIUrl":"https://doi.org/10.1016/j.kint.2025.04.016","url":null,"abstract":"INTRODUCTIONVascular calcification is prevalent in chronic kidney disease (CKD), but existing medical treatments fail to achieve satisfactory therapeutic effects. Vascular calcification is now recognized as an active multifactorial process involving diverse mechanisms. Alpha-ketoglutarate (AKG), an intermediate in tricarboxylic acid cycle, has been demonstrated to extend lifespan and ameliorate age-related osteoporosis. However, whether AKG inhibits vascular calcification remains unknown.METHODSHere, mineral deposition was studied with AKG treatment in rodent and human vascular smooth muscle cells (VSMCs) under osteogenic conditions in vivo and in vitro.RESULTSAKG treatment remarkably ameliorated calcification of rat and human arterial rings ex vivo and aortic calcification in CKD rats and mice. Mechanistically, AKG treatment upregulated DNA demethylase ten-eleven translocation 2 (TET2) expression during vascular calcification. Knockdown of TET2 by siRNA and pharmacological inhibition of TET2 by Bobcat339 promoted vascular calcification in rat VSMCs. Bobcat339 also enhanced rat aortic ring calcification. Conversely, TET2 overexpression ameliorated vascular calcification in rat VSMCs, rat aortic rings and CKD rats. Furthermore, VSMC-specific TET2 deficiency promoted aortic calcification in CKD mice. Both TET2 siRNA and Bobcat339 independently counteracted the inhibitory effect of AKG on vascular calcification of rat VSMCs. Inhibitory effect of AKG administration on vascular calcification was reduced in TET2 knockout mice. TET2 overexpression reduced the levels of the NLRP3 inflammasome pathway, cleaved Caspase-1 and IL-1β protein expression in VSMCs and NLRP3 agonist Nigericin-induced cell calcification.CONCLUSIONSOur study demonstrate that AKG attenuates vascular calcification partially via upregulation of TET2 and inhibition of NLRP3 inflammasome, indicating the critical role of epigenetic modifier in vascular calcification. Modulation of TET2 may become a promising strategy for the treatment of vascular calcification.","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"42 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087498","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":"Expanding the spectrum of genetic causes of DNA-specific exonucleaseTREX1 variants in thrombotic microangiopathy.","authors":"Jing-Yi Li,Ji-Cheng Lv,Hong Zhang,Xu-Jie Zhou","doi":"10.1016/j.kint.2025.04.014","DOIUrl":"https://doi.org/10.1016/j.kint.2025.04.014","url":null,"abstract":"INTRODUCTIONThrombotic microangiopathy (TMA) is a complex condition involving endothelial damage and microvascular thrombi. The International Society of Nephrology's HUS International Forum identified genetic variants as crucial for tailored therapies like plasma exchange and anti-complement therapy. Recent studies suggested that new pathogenic genes beyond complement, and coagulation pathways contribute to TMA including TREX1 variants. The protein TREX1, a DNA-specific exonuclease, maintains genome integrity and regulates immune responses by degrading damaged cytosolic DNA. Variants disrupting TREX1's endoplasmic reticulum anchoring can lead to vasculopathy.METHODSWe conducted retrospective in silico studies involving 53 patients with TMA, 94 with IgA nephropathy with microangiopathic lesions, 25 with C3G glomerulopathy and 20 with ANCA-associated vasculitis.RESULTSPathogenic variants of TREX1 were found in 5.7% of patients with TMA and 3.2% of patients with IgA nephropathy with microangiopathic lesions, but none in C3 glomerulopathy or ANCA-associated vasculitis.CONCLUSIONSOur study highlights the importance of TREX1 variants in microvascular diseases, particularly in thrombotic microangiopathy and IgA nephropathy. TREX1's critical role in genome integrity and immune regulation may offer new therapeutic avenues for treatment.","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"5 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087497","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":"Anti-nephrin antibodies guide living donor kidney transplantation in a pediatric patient with primary focal segmental glomerular sclerosis.","authors":"Sandra Habbig,Hanna Debiec,Malha Chedik,Dirk L Stippel,Florian Erger,Alexia Lourenço,Max C Liebau,Pierre Ronco","doi":"10.1016/j.kint.2025.04.015","DOIUrl":"https://doi.org/10.1016/j.kint.2025.04.015","url":null,"abstract":"INTRODUCTIONDisease recurrence after kidney transplantation (KTx) remains a major challenge in patients with primary focal segmental glomerulosclerosis (pFSGS). Antibodies targeting the slit diaphragm protein nephrin have been identified in patients with early disease recurrence. Here, we describe monitoring and effective pre-transplant elimination of anti-nephrin antibodies in an adolescent with pFSGS prior to living-donor KTx.METHODSAnti-nephrin antibodies were assessed in pre- and post-transplant serum samples by ELISA, Western blot and immunoprecipitation using three different nephrin proteins.RESULTSPre-transplant treatment including rituximab and repetitive therapeutic plasma exchanges resulted in effective and sustainable reduction of anti-nephrin antibodies. Allograft function has remained excellent without albuminuria over a follow-up of more than one year. Further analysis showed, that the antibodies were cross-reactive with NEPH3 (filtrin), another key slit diaphragm protein.CONCLUSIONSMonitoring and pre-transplant elimination of anti-slit diaphragm antibodies may become a standard, personalized approach in patients with pFSGS requiring KTx.","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"132 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087501","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 nationwide register-based cohort study examined the association between preeclampsia in mothers and the risk of kidney disease in their offspring.","authors":"Ida Lihme,Saima Basit,Frederikke Lihme,Mette B Damholt,Sarah Hjorth,Ellen A Nohr,Heather A Boyd","doi":"10.1016/j.kint.2025.04.017","DOIUrl":"https://doi.org/10.1016/j.kint.2025.04.017","url":null,"abstract":"INTRODUCTIONWomen with preeclampsia often deliver preterm (under37 weeks gestation). Preterm birth is associated with an increased risk of offspring kidney disease, but whether preeclampsia is independently associated with kidney disease risk is unknown. Here, we conducted a register-based cohort study to explore associations between maternal preeclampsia and offspring kidney disease after accounting for preterm birth.METHODSUsing Cox regression, we estimated hazard ratios (HRs) comparing kidney disease rates, overall and by subtype, in offspring with and without exposure to maternal preeclampsia.RESULTSThe study included 2,288,589 persons born in Denmark 1978-2017 of whom 63,191 were exposed to preeclampsia; 37,782 individuals developed kidney disease during 43,137,193 person-years of follow-up. Offspring exposed to preeclampsia and born at term (37 or more weeks' gestation) were 26% more likely than offspring born at term but not exposed to preeclampsia to develop kidney disease in infancy (HR 1.26, 95% confidence interval [1.09-1.46]), and had increased rates of all kidney disease subtypes except acute kidney disease after one year of age (HR range 1.11 to 1.88). Associations between term preeclampsia and offspring chronic, and unspecified and diabetic kidney disease were strongest after 25 years of age (HRs 1.36, 1.70 and 2.85, respectively). Conversely, there was little evidence that exposure to preeclampsia with preterm delivery was associated with increased rates of offspring kidney disease beyond the first year of life (under 1 year: 1.41, [1.05-1.90]; one year or more: 0.94, [ 0.79- 1.11]).CONCLUSIONSAssociations of maternal term preeclampsia with offspring kidney disease hint at underlying mechanisms different from those potentially explaining established associations with preterm birth.","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"126 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087499","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":"Metabolic Dysfunction Associated Kidney Disease: Pathogenesis and Clinical Manifestations.","authors":"Anip Bansal,Michel Chonchol","doi":"10.1016/j.kint.2025.01.044","DOIUrl":"https://doi.org/10.1016/j.kint.2025.01.044","url":null,"abstract":"In recent years, there have been significant changes in the lifestyle and eating behaviors of the population characterized by increased intake of high-calories food and a sedentary lifestyle without physical activity. The increased prevalence of overweight and obesity has led to metabolic dysfunction and their related complications, such as cardiovascular disease and chronic kidney disease (CKD). The purpose of this review is to highlight the importance, clinical features and pathogenesis of metabolic dysfunction-associated kidney disease (MDAKD). MDAKD is a term that describes kidney disease arising from metabolic dysfunction, often in the context of metabolic syndrome (MetS) and is characterized by the presence of CKD in individuals with metabolic abnormalities such as obesity, insulin resistance, diabetes mellitus, dyslipidemia, and hypertension. MDAKD includes diabetic kidney disease (DKD), obesity-related kidney disease (ORKD) and with increasing recognition of other rarer kidney diseases where metabolic dysfunction may impact progression. MDAKD is part of the spectrum of diseases whose pathogenesis is driven by metabolic dysfunction and has recently led to the proposal of new nomenclature including metabolic dysfunction associated steatotic liver disease (MASLD) and Cardio-Kidney-Metabolic Syndrome (CKM Syndrome). The new terminology of MDAKD provides additional emphasis on the pathogenic role of metabolic dysfunction on kidney disease.","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"36 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083292","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":"Unexpected effect of dexamethasone on acute kidney injury.","authors":"Reiko Inoue,Hiroshi Nishi","doi":"10.1016/j.kint.2025.03.013","DOIUrl":"https://doi.org/10.1016/j.kint.2025.03.013","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"13 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915187","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":"Regulation of podocyte surface proteins by the enzyme A Disintegrin And Metalloproteinase 10 (ADAM10).","authors":"David Rosenbaum,Julia Reichelt,Simonas Gudaitis,Stine Kühne,Stephanie Zielinski,Desiree Loreth,Lukas Blume,Johannes Brand,Helga Vitzthum,Wiebke Sachs,Alina Lampert,Lisa Seipold,Matthias Voss,Catherine Meyer-Schwesinger,Paul Saftig","doi":"10.1016/j.kint.2025.04.010","DOIUrl":"https://doi.org/10.1016/j.kint.2025.04.010","url":null,"abstract":"INTRODUCTIONPodocytes are terminally differentiated cells of the kidney filtration barrier. Their network of interdigitating foot processes embraces the glomerular capillaries and are likely remodeled by cleavage of podocyte surface proteins. The metalloproteinase ADAM10 is a major regulator of such surface protein shedding and was recently implicated in the pathophysiology of antibody-mediated podocyte injury.METHODSHere, we studied the contribution of ADAM10 in podocyte biology in health and disease and analyzed prominently expressed and disease-relevant podocyte membrane proteins in detail. We used genetically deficient mice, ADAM 10 inhibited pig glomeruli, and various in vitro experimental systems where detailed biochemical and imaging techniques were performed.RESULTSWe found that thrombospondin type 1 domain containing 7A (THSD7A) and phospholipase A2 receptor 1 (PLA2R1), both of which are primary membranous nephropathy antigens, accumulated upon ADAM10 inhibition/deficiency. Moreover, increased proteins levels of the foot process adhesion protein β-dystroglycan (β-DG) were found. Detailed biochemical analyses in different experimental systems revealed that THSD7A, PLA2R1, and β-DG are true ADAM10 substrates and subject to γ-secretase-mediated intramembrane proteolysis. These substrates co-localize and interact with the protease in podocytes and their shedding regulates filopodogenesis (THSD7A and β-DG) and cell matrix adhesion (β-DG). ADAM10 substrate usage, but also the stability of the podocyte cell surface proteins, are regulated by tetraspanin (Tspan) 15, which is likewise present at podocyte foot processes. A tricomponent complex of THSD7A/ADAM10/Tspan15 was found, with THSD7A acting as both an ADAM10 substrate and regulator.CONCLUSIONSAltogether, our data emphasizes the importance of ADAM10/Tspan15-mediated regulation of podocyte foot process surface proteins that serve as antigens in primary membranous nephropathy and impact cytoskeletal dynamics.","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"110 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926475","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":"Transgenic human nephrin in Drosophila nephrocytes facilitates variant analysis.","authors":"Julia Melina Wolff,Konrad Lang,Mengmeng Chen,Julian Milosavljevic,Séverine Kayser,Martin Helmstädter,Gerd Walz,Ahmed Abed,Lea Gerstner,Sami Bahar,Maximilian H Ulbrich,Tobias Hermle","doi":"10.1016/j.kint.2025.03.030","DOIUrl":"https://doi.org/10.1016/j.kint.2025.03.030","url":null,"abstract":"INTRODUCTIONNephrin, the key structural protein of the slit diaphragm, is encoded by NPHS1. Pathogenic variants in this gene are the primary cause of congenital nephrotic syndrome. About 400 variants have been described but functional characterization in vitro is very limited.METHODSHere, we express human nephrin in Drosophila nephrocytes, which possess a molecularly conserved slit diaphragm to facilitate functional studies.RESULTSImmunofluorescence of the human transgene revealed assembly into a complex linear architecture after silencing of sns, the Drosophila nephrin. This pattern suggests lateral clustering of human nephrin into a macromolecular configuration which resembles nephrin in vivo but is absent in cultured cells. In Drosophila nephrocytes, transgenic nephrin colocalized with the endogenous slit diaphragm proteins Pyd and Kirre, indicating a hybrid multi-protein complex. Transmission electron microscopy with pre-embedding immunogold labeling revealed an atypical, tubular ultrastructure. The linear nephrin did not adequately restore membrane invaginations, endocytic function or cellular survival, suggesting that proper signaling function requires additional indispensable co-factors. Murine Neph1 alone was insufficient but associated with transgenic nephrin. Notably, the linear nephrin assembly provided a read-out for investigation of patient-derived variants. This distinct pattern was altered in transgenes reflecting patient variants with milder clinical presentation, including novel variant NPHS1-V1241G. The impact on the pattern largely correlated with the age of onset of nephrotic syndrome of the respective variant, as demonstrated by automated image annotation for quantitative evaluation.CONCLUSIONOur findings demonstrate that transgenesis of NPHS1 in nephrocytes is a viable approach for investigation of slit diaphragm formation and precise functional characterization of patient variants.","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"2 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903115","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":"ILC1s drive tissue-aggressive macrophages in experimental lupus nephritis.","authors":"Lennard Ostendorf,Deepak A Rao","doi":"10.1016/j.kint.2025.02.030","DOIUrl":"https://doi.org/10.1016/j.kint.2025.02.030","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"95 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889326","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":"Renal Pathology Society/International Kidney and Monoclonal Gammopathy Research Group Consensus on Pathologic Definitions and Terminology of Monoclonal Gammopathy Associated Kidney Lesions.","authors":"Samih H Nasr,Virginie Royal,Alejandro Best Rocha,Maike Büttner-Herold,Candice Roufosse,Frank Bridoux,Wesam Ismail,Lihong Bu,Lynn D Cornell,Amélie Dendooven,Rajib K Gupta,Shigeo Hara,Vincent Javaugue,Nicolas Kozakowski,Satoru Kudose,Gonzalo P Méndez,Kimberley Oliver,Maria M Picken,Dominick Santoriello,Sanjeev Sethi,Akira Shimizu,Geetika Singh,M Barry Stokes,Su-Xia Wang,Nelson Leung,Glen S Markowitz,Vivette D D'Agati","doi":"10.1016/j.kint.2025.04.007","DOIUrl":"https://doi.org/10.1016/j.kint.2025.04.007","url":null,"abstract":"The spectrum of kidney lesions associated with monoclonal gammopathy has significantly expanded over the past 2 decades, with description of new entities and variants of old entities. Pathologic diagnosis is challenging due to lesional complexity, heterogeneity, and reliance on electron microscopy and ancillary techniques. A lack of precise pathologic definitions and uniform terminology has hampered diagnostic accuracy. To address these challenges, the Renal Pathology Society and International Kidney and Monoclonal Gammopathy Research Group jointly tasked a working group of nephropathologists and nephrologists to establish consensus-based terminology and definitions for monoclonal gammopathy-associated kidney lesions. Participants included experts in the field with international representation. This report presents their recommendations. For each lesion, prerequisite (mandatory) diagnostic criteria and supportive (non-mandatory) features are proposed. New terminology is provided for some lesions. Application of standardized terminology and definitions should help harmonize kidney biopsy diagnosis with precision therapy in the monoclonal gammopathy-associated kidney disorders.","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"18 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885075","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}