Kidney international最新文献

{"title":"Automated chemiluminescence immunoassay for the detection of anti-nephrin autoantibodies.","authors":"Rui Gu, Jiayu Zhang, Chungen Qian, Gang Wang, Mingyu Lai, Jiayi Shen, Jianhua Mao, Qing Ye","doi":"10.1016/j.kint.2026.07.036","DOIUrl":"10.1016/j.kint.2026.07.036","url":null,"abstract":"<p><strong>Introduction: </strong>Circulating anti-nephrin autoantibodies are being increasingly recognized in autoimmune podocytopathies, particularly minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). However, circulating anti-nephrin reactivity is often low, and currently available assays differ substantially in design, antigen production, and analytical performance. This methodological heterogeneity highlights the need for standardized and quantitative assays for clinical application.</p><p><strong>Methods: </strong>Recombinant human nephrin ectodomain-coated magnetic microparticles were used to establish an automated chemiluminescence immunoassay (CLIA). Serum anti-nephrin IgG was measured in 121 children with biopsy-confirmed MCD (n=103) or primary FSGS (n=18), together with disease controls (genetically confirmed MCD/FSGS, IgA nephropathy, IgA vasculitis with nephritis, lupus nephritis, and ANCA-associated glomerulonephritis) and healthy individuals. Samples were tested in parallel by immunoprecipitation-Western blot (IP-WB). Antigen inhibition assays and cohort-based clinical analyses were performed.</p><p><strong>Results: </strong>The CLIA met predefined analytical performance criteria and showed substantial agreement with IP-WB, with an overall concordance of 86.8% and Cohen's kappa coefficient of 0.714. CLIA detected anti-nephrin IgG more frequently than IP-WB in patients with MCD or FSGS (41.3% vs. 28.1%), including additional low-level positive samples. Antigen inhibition assays showed dose-dependent inhibition in CLIA-positive samples. Among patients with baseline nephrotic-range proteinuria, antibody positivity was associated with greater proteinuria, lower serum albumin, and steroid-sensitive nephrotic syndrome. Patients with elevated anti-nephrin IgG levels had significantly shorter relapse-free survival. During complete remission, anti-nephrin IgG positivity was associated with relapse within three months, with relapse risk increasing according to antibody level.</p><p><strong>Conclusions: </strong>Together, our automated CLIA may help move anti-nephrin IgG testing from specialized research workflows toward standardized clinical application, supporting future use in disease stratification and longitudinal monitoring.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017198","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":"Whole-genome sequencing characterizes monogenic and polygenic contributions to structural kidney and urinary tract malformations.","authors":"Melanie M Y Chan, Omid Sadeghi-Alavijeh, Seth du Preez, Catalin D Voinescu, Loes F M van der Zanden, Sander Groen In 't Woud, Michiel F Schreuder, Wout Feitz, Enrico Mingardo, Alina C Hilger, Heiko Reutter, Lisanne M Vendrig, Rik Westland, Glenda M Beaman, William G Newman, Adrian S Woolf, Horia C Stanescu, Adam P Levine, Detlef Böckenhauer, Daniel P Gale","doi":"10.1016/j.kint.2026.07.037","DOIUrl":"10.1016/j.kint.2026.07.037","url":null,"abstract":"<p><strong>Introduction: </strong>Congenital anomalies of the kidneys and urinary tract (CAKUT) are the commonest cause of kidney failure in children and young adults. Over 50 monogenic causes have been identified. However, fewer than 20% of patients have a genetic diagnosis identified using targeted or whole exome sequencing. Here, we characterize the genomic architecture of CAKUT using whole genome sequencing (WGS).</p><p><strong>Methods: </strong>Based on WGS data from 1,052 unrelated individuals with CAKUT recruited to the UK's 100,000 Genomes Project, we used a panel-based framework to determine diagnostic yield and looked for gene-based enrichment of rare variants exome-wide. We performed sequencing-based genome-wide association studies (seqGWAS) and estimated the heritability attributable to common and low frequency variants.</p><p><strong>Results: </strong>The overall diagnostic yield was 4.9%, increasing to 7.4% in those with kidney agenesis/hypodysplasia and 11.1% in cystic kidney dysplasia. Family history (odds ratio (OR) 2.2; 95% confidence interval (CI) 1.1-4.4), consanguinity (OR 3.0; 95%CI 1.2-6.9) and extra-renal features (OR 3.1; 95% CI 1.7-5.7) independently predicted a monogenic diagnosis. Exome-wide rare variant and genome-wide common and low-frequency variant (minor allele frequency [MAF] 0.5% or more) association testing in a subset of 813 patients and 25,205 ancestry-matched control individuals identified a genome-wide significant association at 6q16.3 (rs117473527; OR 3.13; 95% CI 2.08-4.72; P = 4.8x10^-8; MAF 0.01) requiring replication. Common and low-frequency variants were estimated to explain 23% (95% CI 1-45%) of the phenotypic variance observed in CAKUT although the confidence intervals were wide. A polygenic risk score for posterior urethral valves was constructed and validated in an independent European cohort of 77 cases and 2746 controls.</p><p><strong>Conclusions: </strong>The diagnostic yield for monogenic kidney disease was only 4.9% in this cohort, with common and low frequency variants potentially accounting for some of the missing heritability of CAKUT.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017152","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":"Androgens drive SOX9 upregulation in injured proximal tubular cells.","authors":"Corynne Vermillion Allison, Prisha S Patel, Qiao Xuanyuan, Amanda Stayton, Milon Mondal, Josie A Silvaroli, Isaac Z Karel, Victoria C Thorson, Gabriella Sloane, Helena Joseph Thailammanal, Yogesh Scindia, Christopher C Coss, Diana Zepeda-Orozco, Reena Rao, Subhashini Bolisetty, Sandeep K Mallipattu, Benjamin D Humphreys, Amandeep Bajwa, Navjot S Pabla, Jiyoung Kim","doi":"10.1016/j.kint.2026.07.038","DOIUrl":"10.1016/j.kint.2026.07.038","url":null,"abstract":"<p><strong>Introduction: </strong>Sex influences susceptibility, recovery, and long-term outcomes after acute kidney injury (AKI) in humans. Rodent models have been invaluable for elucidating AKI mechanisms. However, most studies have focused on males, assuming direct applicability to females, an assumption that remains largely untested. In males, the transcription factor SOX9 regulates injury-associated proximal tubule cell states, promoting adaptive repair and survival in the early phase while contributing to fibrosis in later phases. Given the well-described role of SOX9 in sex determination during development and its emerging importance in AKI, we investigated whether it mediates sex-specific tubular responses in the adult kidney.</p><p><strong>Methods: </strong>We first optimized differential ischemic and cisplatin conditions in males and females to generate injury-matched models. We then used these models to ask whether proximal tubular cell responses, particularly Sox9 upregulation, are sex dependent. Tubule-specific knockout models of Sox9, Sox4, Sox11, Vgf, Zfp24, and the androgen receptor (Ar), along with gonadectomy and hormone replacement studies, combined with gene and protein analyses, were used to define regulatory networks.</p><p><strong>Results: </strong>Under injury-matched conditions, biomarkers such as NGAL and KIM1 were equally induced in the kidneys of both sexes. However, Sox9 and its downstream target Vgf showed markedly blunted induction in females. Consistent with male-specific Sox9 induction, the upstream transcription factor Zfp24 was dephosphorylated and activated only in males. Deletion of Sox9, Zfp24, or Vgf worsened injury in males but not in females. In contrast, Sox4 and Sox11 were equally upregulated and protective in both sexes. Castration or proximal tubule-specific deletion of Ar in males abolished Sox9 induction, establishing a testosterone-dependent regulatory axis.</p><p><strong>Conclusions: </strong>Our findings define a hormone-driven, male-specific tubular repair program and demonstrate that injury and recovery pathways differ fundamentally between sexes, underscoring the need for sex-inclusive therapeutic strategies for AKI.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017184","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 Renal Iohexol Clearance Survey examined whether testosterone is a risk factor for age-related measured glomerular filtration rate decline in males.","authors":"Vetle Saastad, Ludvig B Rinde, Inger T Enoksen, Guri Grimnes, Bjørn O Eriksen, Toralf Melsom","doi":"10.1016/j.kint.2026.07.030","DOIUrl":"10.1016/j.kint.2026.07.030","url":null,"abstract":"<p><strong>Introduction: </strong>Testosterone has been hypothesized to contribute to glomerular filtration rate (GFR) decline in males through its effects on kidney cells and the renin-angiotensin system. However, prior research relied on creatinine-based estimated GFR (eGFR), which may be biased by the association between testosterone and muscle mass, as increased muscle mass raises serum creatinine independently of true GFR. Here, we investigate the association between serum levels of total testosterone (TT), free testosterone (FT), and sex hormone-binding globulin (SHBG) and age-related decline in measured GFR (mGFR).</p><p><strong>Methods: </strong>We included a representative sample of 800 males aged 50-62 years old from the general population without self-reported cardiovascular disease, diabetes, or kidney disease. All participants underwent plasma iohexol clearance measurements between 2007-2009, with follow-ups in 2013-2015 (656 individuals) and 2018-2020 (578 individuals). The association of FT, TT, and SHBG with mGFR decline and accelerated mGFR decline, defined as the 10% with the steepest GFR decline (-1.64 mL/min per 1.73 m² or more per year), was assessed using linear mixed models and logistic regression.</p><p><strong>Results: </strong>Both TT and SHBG were associated with a higher mGFR at baseline (0.27 ml/min/1.73 m² [95% confidence interval: 0.09-0.45] per 1 nmol/L higher TT and 0.79 ml/min per 1.73 m² [0.18- 1.41] per 10 nmol/L higher SHBG). Neither TT, FT, nor SHBG were associated with mGFR decline in the multivariable-adjusted linear mixed model analyses (-0.02 [-0.04 to 0.01] and -0.03 [-0.15 to 0.08] ml/min per 1.73 m² per year for each nmol/L increase in TT and FT, respectively, and -0.04 [-0.12 to 0.05] ml/min per 1.73 m² per year for each 10 nmol/L increase in SHBG).</p><p><strong>Conclusions: </strong>Testosterone was not associated with age-related GFR decline in males aged 50 to 62 years at baseline in the general population over a median follow-up of 10.9 years.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982922","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 randomized cross-over trial of pre-and post-filter hemodiafiltration modalities in children on maintenance dialysis -- effects on solute removal and blood pressure","authors":"Ayse Agbas, Nur Canpolat, Bruno Ranchin, Claus Peter Schmitt, Sacha Flammier, Miriam Scwetlick, Lynsey Stronach, Kathryn Waters, Seha Saygili, Evelien Snauwaert, Sunny Eloot, Fabio Paglialonga, Flavia Prodam, Sabrina Tini, Salim Çalıskan, Rukshana Shroff","doi":"10.1016/j.kint.2026.07.032","DOIUrl":"https://doi.org/10.1016/j.kint.2026.07.032","url":null,"abstract":"Children on post-filter hemodiafiltration (post-HDF) have reduced cardiovascular damage and improved growth compared to conventional hemodialysis. High convection volumes in post-HDF are associated with improved outcomes. Even higher convection volumes can be reached with pre-filter HDF (pre-HDF). However, data is limited. Here, we compare the effect of pre- vs post-HDF on solute removal, inflammation, nutrition markers and blood pressure in a randomized, multicenter cross-over trial.","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"22 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148979376","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":"Resident immune cell neighborhoods associate with protein kinase pRIPK3 and fatty acid ligase FACL4 expression during cell injury in ANCA associated vasculitis and lupus nephritis.","authors":"Marlene Weiß, Megan L Baker, Tifanny Budiman, Gabriel Lerner, Ashish Shelar, Dennis G Moledina, Vijayakumar R Kakade, Lloyd G Cantley","doi":"10.1016/j.kint.2026.07.031","DOIUrl":"10.1016/j.kint.2026.07.031","url":null,"abstract":"<p><strong>Introduction: </strong>Tubulointerstitial injury is a key determinant of kidney prognosis and progression to chronic kidney disease in both antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and lupus nephritis (LN). Identification of immune cell-induced injury of cells outside the glomerulus in vasculitic kidney diseases may inform potential targets for therapeutic interventions.</p><p><strong>Methods: </strong>To identify these cells, kidney biopsy samples from 15 patients (5 AAV, 5 class III and IV LN, 5 reference) were analyzed at single cell resolution using Imaging Mass Cytometry.</p><p><strong>Results: </strong>Unbiased clustering of all 106,455 cells identified the expected resident tubule, endothelial, vascular and stromal cells, along with a marked increase in interstitial immune cells. Quantification of cell marker expression in resident cell clusters revealed downregulation of cell differentiation markers and upregulation of phosphorylated protein kinase RIPK3 and fatty acid ligase FACL4 in multiple tubule segments and endothelial cells in both AAV and LN compared to reference samples (non-tumor regions of nephrectomy samples). Spatially, these injury markers were increased in resident cells that were immediately adjacent to immune cells and in particular T cells.</p><p><strong>Conclusions: </strong>Our hypothesis-generating study shows that distinct immune cells are spatially associated with specific cell injury responses in the tubulointerstitium and identify pRIPK3 and FACL4 expression as potential integral components of that injury and cell death response.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977198","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 Disease: Improving Global Outcomes (KDIGO) response to the retraction of the ADVOCATE trial publication on avacopan for the treatment of ANCA-associated vasculitis.","authors":"Brad H Rovin, David R W Jayne, Jan-Stephan F Sanders, Vladimír Tesar, Jürgen Floege","doi":"10.1016/j.kint.2026.08.012","DOIUrl":"10.1016/j.kint.2026.08.012","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912652","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":"Skeletal oxalosis in a child on maintenance hemodialysis.","authors":"Zhengwen Xing, Ping Wang, Xiaoe Zhang, Liyin Zhang, Yulin Kang, Weihua Zheng, Shaojun Liu, Ying Wu","doi":"10.1016/j.kint.2026.08.009","DOIUrl":"10.1016/j.kint.2026.08.009","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881068","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":"An invisible bladder stone causing silent obstructive kidney failure.","authors":"Jing-Huan Liao, Chin-Li Chen, Shun-Neng Hsu","doi":"10.1016/j.kint.2026.08.011","DOIUrl":"10.1016/j.kint.2026.08.011","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881016","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 polycystic kidney as a staphylococcal reservoir.","authors":"Juliette Leon, Pauline Brocard, Clara Tescher, Guillaume Reichert, Antoine Troger, Dany Anglicheau, Aurélie Hummel, Dominique Joly","doi":"10.1016/j.kint.2026.08.010","DOIUrl":"10.1016/j.kint.2026.08.010","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881051","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}