Kidney international最新文献

{"title":"A MEF2C transcription factor network regulates proliferation of glomerular endothelial cells in diabetic kidney disease","authors":"Ricardo Melo Ferreira ,&nbsp;Debora L. Gisch ,&nbsp;Carrie L. Phillips ,&nbsp;Ying-Hua Cheng ,&nbsp;Nicholas Lucarelli ,&nbsp;Soumya Yennapureddy ,&nbsp;Maansi Asthana ,&nbsp;Blue B. Lake ,&nbsp;William S. Bowen ,&nbsp;Fang Fang ,&nbsp;Mahla Asghari ,&nbsp;Angela Sabo ,&nbsp;Daria Barwinska ,&nbsp;Michael J. Ferkowicz ,&nbsp;Robert D. Toto ,&nbsp;John R. Sedor ,&nbsp;Sylvia E. Rosas ,&nbsp;Petter Bjornstad ,&nbsp;Jeffrey B. Hodgin ,&nbsp;Charles E. Alpers ,&nbsp;Michael T. Eadon","doi":"10.1016/j.kint.2026.03.020","DOIUrl":"10.1016/j.kint.2026.03.020","url":null,"abstract":"<div><h3>Introduction</h3><div>The maintenance of a healthy epithelial-endothelial juxtaposition requires crosstalk within glomerular cellular niches. Here, we sought to understand the spatially anchored regulation and transition of endothelial and mesangial cells from health to injury in DKD.</div></div><div><h3>Methods</h3><div>From 132 human kidney samples, an integrated multiomics approach was leveraged to identify cellular niches, cell-cell communication, cell injury trajectories, and regulatory transcription factor networks in glomerular capillary endothelial (EC-GC) and mesangial cells. Data were culled from single nucleus RNA, ATAC-sequencing and four orthogonal spatial transcriptomic technologies for correlation with histopathological and clinical trial data.</div></div><div><h3>Results</h3><div>We identified a cellular niche in diabetic glomeruli enriched in a proliferative endothelial cell subtype (prEC) and altered vascular smooth muscle cells (VSMCs). Cellular communication within this niche maintained pro-angiogenic signaling with loss of anti-angiogenic factors. We identified a transcription factor network of MEF2C, MEF2A, and TRPS1 which regulated SEMA6A and PLXNA2, a receptor-ligand pair opposing angiogenesis. <em>In silico</em> knockout of the transcription factor network accelerated the transition from healthy EC-GCs toward a degenerative injured endothelial phenotype, with concomitant disruption of EC-GC and prEC expression patterns. Glomeruli enriched in the prEC niche had histologic evidence of neovascularization. MEF2C activity was increased in diabetic glomeruli with nodular mesangial sclerosis. The gene regulatory network (GRN) of MEF2C was dysregulated in EC-GCs of patients with DKD, but sodium glucose transporter-2 inhibitor (SGLT2i) treatment reversed the MEF2C GRN effects of DKD.</div></div><div><h3>Conclusions</h3><div>The MEF2C, MEF2A, and TRPS1 transcription factor network carefully balances the fate of the EC-GC in DKD. When the transcription factor network is “on” or over-expressed in DKD, EC-GCs may progress to a prEC state, while transcription factor suppression leads to cell death. SGLT2i therapy may restore the balance of MEF2C activity.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"110 1","pages":"Pages 227-244"},"PeriodicalIF":21.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775533","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":"Intercalated cell subtype identity is controlled by reciprocal suppression of transcription factors","authors":"Jonathan M. Barasch,&nbsp;Qais Al-Awqati","doi":"10.1016/j.kint.2026.02.008","DOIUrl":"10.1016/j.kint.2026.02.008","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"110 1","pages":"Pages 26-28"},"PeriodicalIF":21.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147359012","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 testing in kidney transplantation and living kidney donor risk assessment","authors":"Clara Schott,&nbsp;Sydney Relouw,&nbsp;Monica Arnaldi,&nbsp;Cadence Baker,&nbsp;Gabriela Offerni-Almada,&nbsp;Jian Wang,&nbsp;Adam D. McIntyre,&nbsp;Surim Son,&nbsp;Meaghan Cuerden,&nbsp;Jennifer B. Arnold,&nbsp;Nikita Burman,&nbsp;Samantha Colaiacovo,&nbsp;Karla Solo,&nbsp;Neil Boudville,&nbsp;Christine Dipchand,&nbsp;Liane S. Feldman,&nbsp;John Gill,&nbsp;Lakshman Gunaratnam,&nbsp;Andrew A. House,&nbsp;Hariharan Iyer,&nbsp;Dervla M. Connaughton","doi":"10.1016/j.kint.2026.02.033","DOIUrl":"10.1016/j.kint.2026.02.033","url":null,"abstract":"<div><h3>Introduction</h3><div>The cause of kidney failure in kidney transplant recipients remains unknown in 20–45% of cases. Outcomes for living kidney donors (LKDs) are generally excellent, with only 8% experiencing complications post-donation. Here, we hypothesize that genetic testing could identify a genetic etiology in at least 20% of recipients and inform risk stratification in LKDs.</div></div><div><h3>Methods</h3><div>Genetic testing was performed in 231 transplant recipients and 46 prospective LKDs by means of exome sequencing of 409 chronic kidney disease (CKD)-associated genes. We also assessed 122 retrospective LKDs who developed adverse kidney outcomes post-donation which were defined by at least two of the three criteria: hypertension, a glomerular filtration rate under 60 mL/min/1.73m², or a urine albumin to creatinine ratio of 3 mg/mmol or more.</div></div><div><h3>Results</h3><div>Pathogenic or likely pathogenic (P/LP) variants were identified in 23% of recipients, most commonly involving genes associated with cystic kidney disease and glomerulopathies. Among the recipients with a genetic diagnosis, there was a 37% rate of reclassification to a different phenotype post genetic testing. Among prospective LKDs, 4% had P/LP variants. In the retrospective cohort of LKDs with adverse kidney outcomes post donation, 19% carried P/LP variants.</div></div><div><h3>Conclusions</h3><div>Genetic testing yielded a high diagnostic rate and frequently reclassified CKD etiology in transplant recipients, underscoring its diagnostic utility. Universal genetic testing of asymptomatic LKDs had a yield of 4%, although our prospective LKD cohort had limited sample size. In contrast, high proportion of LKDs with adverse kidney outcome post-donation were found to carry P/LP variants in CKD-associated genes. Our findings suggest that targeted genetic testing of high-risk donors may be a preferred over universal testing strategy to optimize donor selection in LKDs. However, further evaluation is warranted to ensure this approach appropriately balances donor safety with equitable access.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"110 1","pages":"Pages 190-205"},"PeriodicalIF":21.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147535720","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":"What does it mean to win? Interpreting hierarchical kidney outcomes in hypertension trials","authors":"Amélie Bernier-Jean","doi":"10.1016/j.kint.2026.04.012","DOIUrl":"10.1016/j.kint.2026.04.012","url":null,"abstract":"<div><div>Hierarchical composite kidney outcomes analyzed using win statistics prioritize important events while avoiding some limitations of traditional composite end points. Liu <em>et al.</em> apply this approach to 4 large hypertension trials. Their analysis illustrates how hierarchical comparisons behave when major kidney events are uncommon and most comparisons are resolved by lower-tier outcomes, in this case estimated glomerular filtration rate slope. In these settings, the win statistic largely reflects kidney function trajectories, making interpretation dependent on how slope is measured and defined.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"110 1","pages":"Pages 35-38"},"PeriodicalIF":21.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148277836","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":"Light chain crystalline podocytopathy and tubulopathy","authors":"Jing Xu ,&nbsp;Chenyang Qi ,&nbsp;Hao Shi ,&nbsp;Xiaoxia Pan","doi":"10.1016/j.kint.2025.12.030","DOIUrl":"10.1016/j.kint.2025.12.030","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"110 1","pages":"Page 263"},"PeriodicalIF":21.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446967","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":"Unique aspects of acute kidney injury associated with infections in the tropics: presentation, challenges, and opportunities","authors":"Mythri Shankar ,&nbsp;Sabine Karam ,&nbsp;Sola Aoun Bahous ,&nbsp;Bianca Davidson ,&nbsp;Vivek Kumar ,&nbsp;Sourabh Sharma ,&nbsp;Kornchanok Vareesangthip ,&nbsp;Mitchell H. Rosner ,&nbsp;Eranga Wijewickrama","doi":"10.1016/j.kint.2026.02.025","DOIUrl":"10.1016/j.kint.2026.02.025","url":null,"abstract":"<div><div>“The tropics” currently account for around 40% of the world’s population and face unique environmental challenges, with limited resources, a deficient health system, and a rudimentary sanitary infrastructure, in addition to a lack of adequate preventive measures and poor surveillance programs. Cases of acute kidney injury in the tropics are to a very large extent driven by infections such as leptospirosis, scrub typhus, dengue, malaria, Ebola virus, yellow fever, and HIV, with a pathogenesis driven by volume depletion, hypotension, and immune-mediated mechanisms. Many of these infections also lead to multiorgan failure and significant morbidity and mortality. Delayed diagnosis and limited access to kidney replacement therapy can further worsen the prognosis. Investment in preventive measures such as vector control, clean water access, robust vaccination programs, and health system strengthening is vital to reduce the incidence and severity of infection-associated acute kidney injury in the tropics.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"110 1","pages":"Pages 61-69"},"PeriodicalIF":21.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147495192","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":"Proteinase 3 drives murine diabetic kidney disease by mediating caspase-3-dependent apoptosis of podocytes","authors":"Fangyu Wan,&nbsp;Bei Yang,&nbsp;Jufei Li,&nbsp;Lin Lin,&nbsp;Mengjie Kong,&nbsp;Zheng Ni,&nbsp;Zhikang Cen,&nbsp;Mengqi Fan,&nbsp;Wen Zhang,&nbsp;Shuangxin Liu,&nbsp;Yang Xiao,&nbsp;Xuejing Zhu,&nbsp;Zixuan Yi,&nbsp;Ranyao Yang,&nbsp;Jie Chen,&nbsp;Yuying Zhang,&nbsp;Haiyong Chen,&nbsp;Yuewei Ge,&nbsp;Shufei Zang,&nbsp;Guozhi Jiang,&nbsp;Dewei Ye","doi":"10.1016/j.kint.2026.02.020","DOIUrl":"10.1016/j.kint.2026.02.020","url":null,"abstract":"<div><h3>Introduction</h3><div>Podocytes play a pivotal role in maintaining homeostasis of the glomerular filtration barrier. Podocyte loss represents a critical event that contributes to the development of diabetic kidney disease (DKD). Nonetheless the key mediators and mechanisms underlying DKD-associated podocyte death remain poorly characterized. Proteinase 3 (PR3) is a serine protease with selective high abundance in myeloid cells and pleiotropic effects on the regulation of innate immunity.</div></div><div><h3>Methods</h3><div>An experimental DKD model was induced by a combination strategy of uninephrectomy, intraperitoneal injection of streptozocin, and feeding of a high-fat diet in global or podocyte-specific PR3 knockout mice and their controls. Mouse primary podocytes lacking PR3 or conditionally immortalized murine podocytes overexpressing PR3 were incubated with high glucose to trigger apoptosis. Adeno-associated viruses expressing the serine protease inhibitor elafin were injected locally into mouse kidney to inhibit kidney PR3.</div></div><div><h3>Results</h3><div>PR3 abundance in the kidney was markedly increased, predominantly in podocytes, in mouse models of DKD. Global or podocyte-specific genetic ablation of PR3 significantly attenuated severe proteinuria, mesangial matrix expansion, and podocyte injury in diabetic mice. Mechanistically, the lysates from mouse primary podocytes with high glucose-elicited PR3 enrichment and enhanced enzymatic activity induced cleavage of procaspase-3 and triggered podocyte apoptosis that was substantially alleviated in the presence of genetic ablation or pharmacological inhibition of PR3. Adenovirus-mediated overexpression of PR3 markedly potentiated caspase-3 cleavage and cell apoptosis in conditionally immortalized murine podocytes. In contrast, a lack of PR3 protected against adriamycin-induced podocytopathy in mice, further confirming PR3 as a driving force of podocyte injury. Therapeutically, kidney overexpression of elafin significantly attenuated podocyte loss and other DKD-like traits in mice.</div></div><div><h3>Conclusions</h3><div>Our results demonstrate that podocyte-derived PR3 induces caspase-3 cleavage to mediate podocyte apoptosis, thereby potentiating DKD progression, suggesting that pharmacological intervention of podocyte-derived PR3 may represent a promising therapeutic strategy for DKD.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"110 1","pages":"Pages 115-129"},"PeriodicalIF":21.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147448361","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":"Subscription Information","authors":"","doi":"10.1016/S0085-2538(26)00343-1","DOIUrl":"10.1016/S0085-2538(26)00343-1","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"110 1","pages":"Page A3"},"PeriodicalIF":21.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148571578","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 prospective multicenter randomized controlled trial pre-emptive increase in immunosuppression for asymptomatic serological reactivation in patients with lupus nephritis in clinical remission","authors":"Desmond Y.H. Yap,&nbsp;Shirley C.W. Chan,&nbsp;Patrick Y.H. Wong,&nbsp;Sunny Wong,&nbsp;Danting Zhang,&nbsp;Susan Yung,&nbsp;Joseph M.W. Lo,&nbsp;Chak Sing Lau,&nbsp;Colin Tang,&nbsp;Tak Mao Chan","doi":"10.1016/j.kint.2026.02.037","DOIUrl":"10.1016/j.kint.2026.02.037","url":null,"abstract":"<div><h3>Introduction</h3><div>The management of patients with lupus nephritis (LN) in clinical remission who demonstrate asymptomatic serological reactivation remains uncertain. Results from our previous study suggested that a pre-emptive moderate increase of immunosuppressive treatment might reduce disease flares.</div></div><div><h3>Methods</h3><div>Here, we conducted a prospective multicenter randomized controlled trial to compare pre-emptive treatment (PT) against observant management (Control) in clinically stable patients with LN and asymptomatic serological reactivation who were receiving low-dose glucocorticoid and mycophenolate or azathioprine as maintenance immunosuppression. PT included an increase in prednisolone dose from ≤5 mg/d to 0.4-0.5 mg/kg/d and an increase in mycophenolate or azathioprine dose to 1.5 g/d and 100 mg/d, respectively, followed by tapering of prednisolone dose to the original level by 12 weeks. Patients were followed for 24 months from randomization. The primary outcome was 24-month survival free of kidney flares. Secondary outcomes included survival free of extra-kidney flares, change in kidney and immunological parameters, and adverse events.</div></div><div><h3>Results</h3><div>Forty-nine patients were randomized (24 PT and 25 Control). No kidney flare occurred in PT while five kidney flares occurred at 6.0 (interquartile range: 3.0-10.0) months in Controls. PT patients had superior 24-month survival free of kidney, extra-kidney, and overall flares than Controls (100% vs. 80%, 91% vs. 72%, and 91% vs. 52%, respectively, significant for all). PT patients showed improved anti-dsDNA and C3 compared to baseline, but not patients in the Control arm. Adverse events were few and similar, and kidney function remained stable in both groups.</div></div><div><h3>Conclusions</h3><div>A pre-emptive moderate increase of immunosuppression was effective in preventing kidney flares in patients with LN and with asymptomatic serological reactivation and was well tolerated.</div></div><div><h3>Trial Registration</h3><div>Registered at <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> with study number <span><span>NCT04870359</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"110 1","pages":"Pages 245-254"},"PeriodicalIF":21.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147536503","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":"Advances in survival analyses: machine learning methods and model comparison","authors":"Ryan Gately,&nbsp;Dharshana Sabanayagam,&nbsp;Wai H. Lim,&nbsp;Lin Zhu,&nbsp;Farzaneh Boroumand,&nbsp;Shuvo Bakar,&nbsp;Armando Teixeira-Pinto,&nbsp;Germaine Wong","doi":"10.1016/j.kint.2026.02.041","DOIUrl":"10.1016/j.kint.2026.02.041","url":null,"abstract":"<div><div>This is the second article in a 2-part series on survival analysis. In part 1, we discussed the core concepts and traditional methods used in survival analysis. Part 2 explores the novel approaches to predict survival outcomes and evaluate model performance. To facilitate hands-on learning and practical implementation, the R code used in these analyses is provided in the supplementary materials, along with instructions to help readers apply these methods to their data.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"110 1","pages":"Pages 78-88"},"PeriodicalIF":21.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816800","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}