Kidney international最新文献

{"title":"Lupus nephritis treat to target normalizing anti-dsDNA, C3, and C4 is a bridge too far","authors":"H. Michael Belmont","doi":"10.1016/j.kint.2025.01.031","DOIUrl":"10.1016/j.kint.2025.01.031","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 5","pages":"Page 937"},"PeriodicalIF":14.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844860","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":"Clarifying the interpretation of semaglutide’s impact in the FLOW study","authors":"Maxime Ingwiller","doi":"10.1016/j.kint.2025.01.028","DOIUrl":"10.1016/j.kint.2025.01.028","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 5","pages":"Pages 939-940"},"PeriodicalIF":14.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844864","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":"Genetic studies on metabolic disorder associated kidney diseases.","authors":"Minako Imamura,Takashi Kadowaki,Maeda Shiro","doi":"10.1016/j.kint.2025.01.042","DOIUrl":"https://doi.org/10.1016/j.kint.2025.01.042","url":null,"abstract":"Diabetic kidney disease (DKD) and obesity-related kidney diseases are the representative chronic kidney diseases related to metabolic disorders. Genome-wide association studies (GWAS) have been extensively performed, and a substantial number of confirmed loci have been identified to be associated with many common diseases or quantitative traits, including type 2 diabetes, obesity, and chronic kidney diseases. By contrast, GWAS for DKD have identified limited number of susceptible loci, and the robust replication of these loci in independent studies has not yet been accomplished. As of 2024, no GWAS have been reported on obesity-related kidney diseases. Therefore, the genetic studies on DKD or obesity-related kidney diseases have not provided satisfiable results. However, by genetic correlation studies and Mendelian Randomization studies, that were performed using multi-traits GWAS data suggested that DKD, obesity-related kidney diseases, and obesity share common genetic mechanisms. Since obesity or overweight is a reversible condition, the effective interventions to reduce body weights might contribute to the prevention of the development of not only obesity-related kidney diseases, but also DKD or other types of chronic kidney diseases. Further genetic studies are necessary to understand the genetic architecture of DKD and obesity-related kidney diseases, and should be expanded.","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"267 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853090","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 stratification of metabolic disorder–associated kidney disease","authors":"Xin Xu ,&nbsp;Xian Shao ,&nbsp;Fan Fan Hou","doi":"10.1016/j.kint.2025.01.041","DOIUrl":"10.1016/j.kint.2025.01.041","url":null,"abstract":"<div><div>During the last 20 years, the disease burden attributable to metabolic disorders increased by 49.4%. Metabolic disorders are established risk factors for both chronic kidney disease (CKD) and cardiovascular disease (CVD). A concept of cardiovascular-kidney-metabolic (CKM) syndrome has recently been proposed to underscore the pathophysiological interrelatedness of the metabolic risk factors, CKD, and CVD. Two major adverse outcomes of the metabolic disorder–associated kidney disease are cardiovascular disease and, to a less extent, kidney failure. This review aims to briefly summarize the traditional metabolic risk factors for kidney disease; to introduce the concept of CKM health; to present the methods for risk assessment for CKD progression and CVD, with focus on validated and clinically applicable prediction tools; and to discuss the key gaps in the current tools for the risk stratification. In summary, in general clinical settings, the CKM health and associated risk in patients with the metabolic disorder–associated kidney disease can be assessed by combining the CKM staging model, the CKD Prognosis Consortium equations for CKD progression, and the Predicting Risk of CVD Events (PREVENT) equations for CVD. More efficient risk prediction tools, potentially incorporating multimodal data, are needed for more accurate and early identification of individuals at high risk and better personalized management of the disease.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 6","pages":"Pages 1002-1010"},"PeriodicalIF":14.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743588","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 population-based cohort study defined estimated glomerular filtration rate decline and kidney failure among Canadian immigrants","authors":"Ida-Ehosa Olaye ,&nbsp;Chengchun Yu ,&nbsp;Meltem Tuna ,&nbsp;Ayub Akbari ,&nbsp;Tim Ramsay ,&nbsp;Peter Tanuseputro ,&nbsp;Istvan Mucsi ,&nbsp;Greg A. Knoll ,&nbsp;Manish M. Sood ,&nbsp;Gregory L. Hundemer","doi":"10.1016/j.kint.2025.02.029","DOIUrl":"10.1016/j.kint.2025.02.029","url":null,"abstract":"<div><div>The link between immigrant status, a key social determinant of health, and kidney disease remains uncertain. To evaluate this, we compared incident adverse kidney outcomes between immigrants and non-immigrants using Canadian provincial health administrative data. We conducted a population-based observational cohort study of all adult Ontario residents (immigrants and non-immigrants) with normal baseline kidney function (estimated glomerular filtration rate (eGFR) 70 mL/min/1.73m² or more). Multivariable Cox proportional hazard regression modeling was used to evaluate the relationship between immigrant status and the composite adverse kidney outcome of 40% eGFR decline or kidney failure. The study cohort included 10,440,210 individuals with 22% immigrants and 78% non-immigrants. The mean (Standard Deviation) age and eGFR were 45 (17) years and 102 (16) mL/min/1.73m², respectively. Immigrants experienced a 27% lower hazard for the composite adverse kidney outcome (adjusted hazard ratio 0.73 [95% Confidence Interval 0.72-0.74]) compared to non-immigrants which was primarily driven by 40% eGFR decline. However, immigrants also experienced a 12% lower hazard for incident kidney failure (0.88 [0.84-0.93]) compared to non-immigrants. Results were consistent upon accounting for the competing risk of death and adjusting for baseline albuminuria. As has been demonstrated with other chronic diseases, these novel findings suggest that a “healthy immigrant effect” also extends to kidney disease. Differential kidney disease outcomes were identified among immigrants based on refugee status and world region of origin which may inform health policy decision-making toward targeted screening strategies and more cost-effective resource allocation for immigrant populations.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 6","pages":"Pages 1088-1098"},"PeriodicalIF":14.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743567","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 in adult Chinese patients with minimal change disease and primary focal segmental glomerulosclerosis.","authors":"Yue Shu, Jing Huang, Lei Jiang, Yi-Miao Zhang, Fang Wang, Xin Wang, Li-Qiang Meng, Xu-Yang Cheng, Gang Liu, Su-Xia Wang, Ming-Hui Zhao, Pierre Ronco, Zhao Cui","doi":"10.1016/j.kint.2025.02.028","DOIUrl":"10.1016/j.kint.2025.02.028","url":null,"abstract":"<p><p>Anti-nephrin autoantibodies have been discovered in patients with minimal change disease (MCD) and primary focal segmental glomerulosclerosis (FSGS), especially in those with active nephrotic syndrome. Here, we investigated the prevalence and clinical significance of anti-nephrin antibodies in 596 adult Chinese patients (436 with MCD and 160 with primary FSGS) diagnosed by kidney biopsy. Anti-nephrin IgG and IgM were detected using ELISA, with validation through antigen-inhibition ELISA and Western blotting. Clinical data at biopsy and during the follow-up period were analyzed. Anti-nephrin antibodies were detected in 43% of all patients, with 30% testing positive for anti-nephrin IgG, 26% for anti-nephrin IgM, and 13.1% for both antibodies. The prevalence of anti-nephrin antibodies was higher in patients with nephrotic-range proteinuria who were not receiving steroids or immunosuppressants (51.1%). Patients with positive anti-nephrin antibodies exhibited more severe nephrotic syndrome, higher rates of relapse, and a shorter relapse-free period compared to those negative for these antibodies. Clinical features were similar between those with IgG and IgM. Notably, patients with both anti-nephrin IgG and IgM had the most severe proteinuria and the highest relapse frequency, suggesting a dose-dependent effect. Longitudinal analysis revealed that anti-nephrin antibodies significantly decreased during clinical remission, while they reappeared preceding proteinuria relapse. Our study shows that anti-nephrin antibodies, including IgG and IgM, are detectable in adult patients with MCD and primary FSGS and are associated with active nephrotic syndrome and frequent relapse. These antibodies may serve as valuable biomarkers and potential therapeutic targets.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730666","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":"Contribution of the glomerular filtration rate slope to the kidney hierarchical composite endpoint","authors":"Dustin J. Little ,&nbsp;Niels Jongs ,&nbsp;Meike Brinker ,&nbsp;Samvel B. Gasparyan ,&nbsp;Patrick Schloemer ,&nbsp;Hiddo J.L. Heerspink","doi":"10.1016/j.kint.2025.03.011","DOIUrl":"10.1016/j.kint.2025.03.011","url":null,"abstract":"<div><h3>Introduction</h3><div>A recent chronic kidney disease (CKD) progression hierarchical composite endpoint (HCE) utilizes the glomerular filtration rate (GFR) slope for participants without a dichotomous event. Here, we evaluated clinical interpretations when HCE analyses are driven by GFR slope comparisons.</div></div><div><h3>Methods</h3><div>Using CKD trial data, we calculated win odds using only GFR slope; dichotomous kidney events and GFR slope; all-cause mortality, dichotomous kidney events, and GFR slope; and all-cause mortality with dichotomous kidney events.</div></div><div><h3>Results</h3><div>Win odds (95% confidence interval) calculated from pairwise GFR slope only comparisons were 1.44 (1.34–1.55), 1.60 (1.49–1.72), 1.19 (1.10–1.28), and 0.82 (0.78–0.86) in the DAPA-CKD, CREDENCE, SONAR, and ALTITUDE trials, respectively. Win odds were similar for the GFR slope only and full kidney HCE with and without mortality.</div></div><div><h3>Conclusions</h3><div>These results support incorporation of GFR slope into the CKD progression HCE and help to interpret the magnitude of treatment effect on kidney HCE estimated with win odds.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 6","pages":"Pages 1104-1107"},"PeriodicalIF":14.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730623","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 new era in nephrology: the role of super-resolution microscopy in research, medical diagnostic, and drug discovery","authors":"Florian Siegerist ,&nbsp;Kirk N. Campbell ,&nbsp;Nicole Endlich","doi":"10.1016/j.kint.2025.01.040","DOIUrl":"10.1016/j.kint.2025.01.040","url":null,"abstract":"<div><div>For decades, electron microscopy has been the primary method to visualize ultrastructural details of the kidney, including podocyte foot processes and the slit diaphragm. Despite its status as the gold standard, electron microscopy has significant limitations: it requires laborious sample preparation, works only with very small samples, is mainly qualitative, and is prone to misinterpretation because of section angle bias. In addition, combining imaging and protein staining with antibodies poses a challenge, limiting electron microscopy’s integration into routine research and diagnostic workflows. As imaging technology advances, super-resolution microscopy, with an optical resolution below 100 nm, presents a promising alternative for detailed insights into glomerular ultrastructure. This review explores various super-resolution techniques, particularly 3-dimensional structured illumination microscopy, and demonstrates how they can be applied to standard histological sections. The 3-dimensional structured illumination microscopy–based measurement procedure—podocyte exact morphology measurement procedure—offers a novel approach to quantifying podocyte foot process morphology and can detect podocyte foot process changes even before proteinuria is present. Furthermore, the podocyte exact morphology measurement procedure can be combined with mRNA detection, multiplex staining, and deep learning algorithms, making it a powerful tool for kidney research, preclinical studies, and personalized diagnostics. This advancement has the potential to accelerate drug development and enhance therapeutic precision, heralding a new era of high-precision nephrology.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 6","pages":"Pages 994-1001"},"PeriodicalIF":14.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730652","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":"Endothelial but not systemic ferroptosis inhibition protects from antineutrophil cytoplasmic antibody–induced crescentic glomerulonephritis","authors":"Anthony Rousselle ,&nbsp;Dörte Lodka ,&nbsp;Janis Sonnemann ,&nbsp;Lovis Kling ,&nbsp;Ralph Kettritz ,&nbsp;Adrian Schreiber","doi":"10.1016/j.kint.2025.02.023","DOIUrl":"10.1016/j.kint.2025.02.023","url":null,"abstract":"<div><div>Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are systemic autoimmune diseases featuring small blood vessel inflammation and organ damage, including necrotizing crescentic glomerulonephritis (NCGN). Persistent vascular inflammation leads to endothelial and kidney cell necrosis. Ferroptosis is a regulated cell death pathway executed by reactive oxygen species and iron-dependent lipid peroxidation culminating in cell membrane rupture. Here we show that ANCA-activated neutrophils induced endothelial cell (EC) death <em>in vitro</em> that was prevented by ferroptosis inhibition with Ferrostatin-1, Liproxstatin-1 and small inhibiting RNA against the enzyme AcylCoA Synthetase Long Chain Family Member 4 (ACSL4). In contrast, neither necroptosis nor apoptosis inhibition affected EC death. Moreover, both ferroptosis inhibitors alleviated lipid peroxide accumulation in EC. Increased lipid peroxidation was detected in kidney sections of AAV mice by immunohistochemistry. We generated MPO^–/– ACSL4^flox Tie2-Cre⁺ mice lacking ACSL4 specifically in EC (ACSL4^ΔEC) to study the significance of endothelial ferroptosis <em>in vivo</em>. ACSL4^ΔEC chimeric mice, but not control mice (ACSL4^WT), were protected from NCGN in an MPO-AAV bone-marrow transplantation model. These data establish that EC ferroptosis contributes to ANCA-induced glomerulonephritis. However, systemic pharmacological ferroptosis inhibition with Ferrostatin-1 or Liproxstatin-1 did not protect from NCGN in a murine AAV model. Ferrostatin-1 treatment both directly activated T-cell proliferation and indirectly myeloid-mediated T-cell proliferation and polarization <em>in vitro</em>. Conceivably, both effects may cancel the beneficial effect of endothelial ferroptosis inhibition. Mechanistically, we describe the importance of EC ferroptosis for the development of AAV. However, the lack of protection with systemic pharmacological ferroptosis inhibition should discourage clinicians from evaluating this treatment strategy in clinical AAV studies.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 6","pages":"Pages 1037-1050"},"PeriodicalIF":14.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692685","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":"Transplantation of human kidney organoids elicited a robust allogeneic response in a humanized mouse model","authors":"Samuel Mon-Wei Yu ,&nbsp;John Yongjoon Choi ,&nbsp;Jamie Kady ,&nbsp;Marina De Cos ,&nbsp;Jenny S. Wong ,&nbsp;Emily King ,&nbsp;Nour Younis ,&nbsp;Nadim Al Rahy ,&nbsp;Soltan Al Chaar ,&nbsp;Houda Djebli ,&nbsp;Siawosh Eskandari ,&nbsp;Stephen Samuel ,&nbsp;Tamara Merhej ,&nbsp;Nivedha Sukumar ,&nbsp;Jia-Ren Lin ,&nbsp;Jia-Yun Chen ,&nbsp;Yilin Xu ,&nbsp;Sandro Santagata ,&nbsp;Astrid Weins ,&nbsp;Melissa Yeung ,&nbsp;Jamil Azzi","doi":"10.1016/j.kint.2025.02.027","DOIUrl":"10.1016/j.kint.2025.02.027","url":null,"abstract":"<div><div>Human kidney organoids derived from embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) have become novel tools for studying various kidney pathologies. Here, we transplanted ESC-derived kidney organoids into humanized mice with a mature human adaptive immune system developed through thymic education. As judged by histology and immunophenotyping, the transplanted HLA-mismatched kidney organoids trigged a robust alloimmune response, characterized by a dense immune cell infiltrate and enhanced memory T cell phenotype in the allograft 30 days post-transplantation. Multiplexed immunofluorescence revealed expression of functional markers of various immune cell infiltrates in response to organoid allografts, mimicking the T cell-mediated rejection process in humans. This validated our model as a novel platform to study various therapeutic strategies to control alloimmunity. Splenocytes isolated from organoid-transplanted hosts showed an alloantigen-specific memory response against 2D kidney organoids <em>ex vivo</em>. Overall, our study indicates that transplanting kidney organoids in humanized mice may be a valuable tool for studying human allogeneic immunity.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 6","pages":"Pages 1011-1016"},"PeriodicalIF":14.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699567","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}