Journal of The American Society of Nephrology最新文献

{"title":"Considerations for using eGFR Slope as an End Point in Clinical Trials.","authors":"Tom Greene, ","doi":"10.1681/asn.0000000919","DOIUrl":"https://doi.org/10.1681/asn.0000000919","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"33 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145296207","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":"Podocyte Metabolic Reprogramming and Targeted Therapy.","authors":"Hongtu Hu,Wei Liang,Guohua Ding","doi":"10.1681/asn.0000000917","DOIUrl":"https://doi.org/10.1681/asn.0000000917","url":null,"abstract":"Podocytes, highly specialized glomerular epithelial cells, are essential for maintaining the filtration barrier integrity, yet they are particularly susceptible to metabolic stress. Recent advances have identified metabolic reprogramming as a central driver of podocyte injury in diverse glomerular diseases, including diabetic kidney disease and focal segmental glomerulosclerosis. Pathological stimuli, such as hyperglycemia, lipotoxicity, oxidative stress, and inflammatory cytokines, lead to profound alterations in podocyte metabolism, encompassing dysregulation of lipid, glucose, amino acid, and ion handling, as well as activation of immunometabolic pathways. These maladaptive changes result in mitochondrial dysfunction, cytoskeletal disorganization, and inflammatory forms of cell death including pyroptosis and ferroptosis. Mechanistic studies have elucidated the roles of nutrient-sensing pathways (AMPK, mTOR, SIRT1), innate immune sensors (NLRP3, cGAS-STING), and metabolic enzymes (CerS6, GLS2, ODC1) in orchestrating this reprogramming. Emerging evidence supports the therapeutic potential of modulating podocyte metabolism, as exemplified by the renoprotective effects of SGLT2 inhibitors, GLP-1 receptor agonists, PPAR agonists, and targeted inhibitors of inflammasome or lipid pathways. This Review synthesizes recent insights into the structural-metabolic coupling in podocytes, dissects the mechanisms of metabolic derangement in disease contexts, and discusses promising therapeutic strategies aimed at restoring metabolic homeostasis. Understanding the intersection between podocyte metabolism and injury response offers novel avenues for the prevention and treatment of chronic glomerular diseases.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"13 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283691","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":"Spatial Transcriptomics Reveals Injured Cells, Signature Genes, and Communication Patterns in the Cyst Microenvironment of Polycystic Kidney Disease.","authors":"Sevtap A Yasinoglu,Claudio Novella-Rausell,Lisanne E Wisse,Kyra L Dijkstra,Ahmed Mahfouz,Hans J Baelde,Dorien J M Peters","doi":"10.1681/asn.0000000894","DOIUrl":"https://doi.org/10.1681/asn.0000000894","url":null,"abstract":"BACKGROUNDChanges in the cyst microenvironment in Polycystic Kidney Disease (PKD) may drive progressive cyst formation. Bulk- and single-cell RNA sequencing have advanced our understanding of altered signaling; however, the lack of spatial information has limited our insights into local gene expression and cellular communication near cysts.METHODSWe used wild-type and Pkd1-deficient mouse kidneys to generate 10x Genomics Visium Spatial Gene Expression datasets. Utilizing our single-cell mouse kidney atlas and single cell sequencing data for spot deconvolution, we enhanced resolution and estimated enriched cell types. We analyzed spatial gene expression patterns and used a cyst-centered analysis to identify cyst-associated gene signature. Cell communication near cysts was investigated, identifying key ligand-receptors. Prioritized key factors were validated in tissues.RESULTSWe observed enrichment of fibroblasts, injury-repair-related cell types, and diverse immune populations in PKD. Injury-repair-related cells were exclusively observed in PKD, predominantly localized within immune cell-dense regions near cysts. These cells collectively contributed to the altered gene expression profile in PKD, including cyst-associated signature genes related to inflammatory processes. Analysis of cellular communication in less-inflamed regions around cysts revealed the involvement of multiple cell types. Key ligand-receptor interactions were associated with cytokine signaling, fibrosis, cellular development, and repair. These included Angpt2, C3, Csf1, Cxcl12, Il34, Gas6, Il16, Mdk, Mif, Ptn, Sfrp2, Spp1, Sdc1, Tnc, Tnfsf12, Wnt5a. In addition, ECM proteins implicated in immune response, ECM remodeling, cell adhesion, and cell signaling were identified, such as Adam9, Adam10, Col1a1, Col3a1, Col4a2, Lamb2, Lamc1, Efnb1, Efnb2, Thbs1, Thbs2, and Vcam1. IHC confirmed expression of Syndecan-1-Collagen IV, Midkine-Integrin β1, CSF-1, Pleiotrophin, and Tenascin-C in cystic kidneys.CONCLUSIONSSpatial transcriptomics in PKD revealed enrichment of (myo)fibroblasts, immune, and injury-repair-related cells near cysts, creating a (pro)inflammatory and (pro)fibrotic niche. Key ligand-receptor and ECM interactions were identified and validated.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"114 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261430","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":"Further Considerations on the Clinical Evaluation of Sotagliflozin in Type 1 Diabetes with CKD.","authors":"Rui Wang,Jiarun Xie,Ming Wang","doi":"10.1681/asn.0000000867","DOIUrl":"https://doi.org/10.1681/asn.0000000867","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"18 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261404","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":"Authors' Reply: Further Considerations on the Clinical Evaluation of Sotagliflozin in Type 1 Diabetes with CKD.","authors":"Vikas S Sridhar,Ayodele Odutayo,Michael J Davies,David Z I Cherney","doi":"10.1681/asn.0000000868","DOIUrl":"https://doi.org/10.1681/asn.0000000868","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"72 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261403","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":"How to Cure Autoimmune Glomerulonephritis and Podocytopathies.","authors":"Hans-Joachim Anders,Stefanie Steiger,Paola Romagnani","doi":"10.1681/asn.0000000912","DOIUrl":"https://doi.org/10.1681/asn.0000000912","url":null,"abstract":"Autoimmune glomerulonephritis (GN) and podocytopathies are immune-mediated kidney diseases with different clinical presentations and histotypes. Traditionally, proteinuria and histotypes are used for prognosis prediction and hence define intensity of immunotherapy. Renin-angiotensin system and sodium-glucose transporter 2 inhibitors are considered as \"supportive care\" and control of proteinuria, seems a primary treatment goal without reasoning the cause of proteinuria. We propose to refine these concepts based on the shared pathophysiology of these diseases: 1. Disease acuity as the primary determinant of therapy. Rapidly progressive GN, relapsing GN, and chronic GN require different priorities. Rapidly progressive GN depends on the level and nephrotoxicity of the involved antibodies and complement activation, and may require immediate complement inhibition and antibody removal from the circulation before a B cell-targeting therapy is initiated to control de novo autoantibody production. 2. Relapsing or chronically active disease need long-term control of immunological activity with a B cell-targeting monotherapy, in case of single autoreactive lymphocyte clones, e.g., in ANCA vasculitis or anti-nephrin/anti-PLA2R-nephrotic syndrome. In contrast, diseases with numerous autoantigens/clones, i.e., lupus nephritis or anti-phospholipid syndrome should benefit from combination therapies, similar to kidney transplantation. 3. All forms of GN and most relapsing podocytopathies lead to glomerulosclerosis and nephron loss, i.e., CKD. This implies CKD management following the latest KDIGO CKD risk matrix and treatment recommendations. In relapsing GN/podocytopathies, CKD care is the second treatment priority; in chronic GNs it becomes the first treatment priority in contrast to \"supportive care\". In relapsing and chronic disease, proteinuria levels may represent either activity, CKD or both; hence, proteinuria alone does not inform treatment choices. This review aims to overcome existing hurdles by redefining treatment pritorities in GNs and podocytopathies based on the underlying autoimmune pathomechanisms to define immunotherapy and by implementing CKD care for conceptual clarity and better long-term outcomes.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"26 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261210","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":"Obesity, Treatment, and Kidney Function Assessment.","authors":"Holly J Kramer","doi":"10.1681/asn.0000000880","DOIUrl":"https://doi.org/10.1681/asn.0000000880","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"3 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254484","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":"Computational Characterization of Lymphocyte Topology on Whole Slide Images of Glomerular Diseases.","authors":"Xiang Li, Manav Shah, Qian Liu, Jin Zhou, Gina Sotolongo, Jeffrey B Hodgin, Laura Mariani, Lawrence Holzman, Andrew R Janowczyk, Jarcy Zee, Kyle J Lafata, Laura Barisoni","doi":"10.1681/ASN.0000000889","DOIUrl":"10.1681/ASN.0000000889","url":null,"abstract":"<p><strong>Background: </strong>The distribution of inflammation in the kidney and its clinical relevance is understudied. This study aims to computationally quantify lymphocyte topology and test its prediction of disease progression.</p><p><strong>Methods: </strong>N=333 NEPTUNE/CureGN participants (N=155 focal segmental glomerulosclerosis, N=178 minimal change disease) with available clinical/demographic data and 1 Hematoxylin & Eosin-stained whole slide image were included. Cortex and lymphocytes were automatically segmented. A novel graph-based clustering algorithm was applied to identify dense versus sparse lymphocytic habitats, from which 26 pathomic features were extracted to capture cell density, connectivity, clustering, and centrality. The association of these pathomic features with disease progression (40% eGFR decline or kidney replacement therapy) was assessed using ElasticNet-regularized Cox proportional hazards models. Clinical and demographic characteristics and percent of interstitial fibrosis and inflammation were added as potential confounders. Kaplan-Meier survival analysis with log-rank test was used to evaluate risk stratification. Two validation strategies were applied: (i) training on NEPTUNE with external validation on CureGN data, and (ii) using an 80/20 data partition of the combined datasets for training and validation, respectively.</p><p><strong>Results: </strong>Unadjusted analysis: 17 features (65%) retained significance after adjustment for standard clinico-demographic variables, Number of K-core in sparse habitat maintained significance (HR=1.29, 95% CI: 1.04-1.61) even after adjustment for lymphocyte density, and Average Degree in dense habitat had borderline significance (HR=1.25, 95% CI: 1.00-1.57) after adjustment for interstitial fibrosis. Multivariable models (clinical/demographic + graph features) achieved validation concordance index of 0.78±0.15 in the CureGN external validation and 0.77±0.06 in the combined internal validation dataset. Time-dependent discrimination showed consistent performance at 3- (AUC: 0.78 vs. 0.76) and 5-year timepoints (AUC: 0.74 vs. 0.76) across validation strategies. Sparse habitat clustering patterns (Maximum of K-core × Number of K-core in sparse habitat: 88% selection frequency) and dense habitat connectivity (Average Degree in dense habitat: 47% selection frequency) were consistently identified as robust predictors alongside clinical variables.</p><p><strong>Conclusions: </strong>The topological characterization of lymphocytic inflammation identified immune habitats, capturing the complexity of patterns of inflammation.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251702","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 Story of Aldosterone Escape.","authors":"Dillan Prasad, Austin Drysch, Deep Upadhyay, Eric G Neilson","doi":"10.1681/ASN.0000000908","DOIUrl":"https://doi.org/10.1681/ASN.0000000908","url":null,"abstract":"<p><strong>Abstract: </strong>Aldosterone escape refers to the spontaneous and compensatory diuresis that occurs in primary aldosteronism to correct and rebalance fluid homeostasis during conditions of sodium retention. Though widely observed in humans and animals, the precise mechanisms underpinning aldosterone escape remain unclear. The escape phenomenon is clinically relevant as primary aldosteronism affects nearly one in ten hypertensive adults and doubles the risk of stroke and atrial fibrillation. Studying the phenomenon provides additional insights into the intricate physiology of renal sodium handling that may inform future development of novel therapeutics. This perspective is a modern account of the complex interplay of renal hemodynamics, hormonal signaling, paracrine modulation, and tubular adaptations underlying aldosterone escape. By reexamining classical and emerging mechanisms, including the WNK system as a potassium-sensitive distal homeostasis mechanism, we suggest a general framework for this remarkable phenomenon.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244876","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":"Class 1 Indications for Coronary Revascularization Identified in Prekidney Transplant Screening.","authors":"Avantika Israni,Bronya L Sandorffy,Celina S Liu,Daniela I Fraticelli Ortiz,Haley M Gross,Joey Nicholson,Miri Cazes,Qandeel H Soomro,Xinyi Zhang,Wenbo Wu,David M Charytan","doi":"10.1681/asn.0000000890","DOIUrl":"https://doi.org/10.1681/asn.0000000890","url":null,"abstract":"BACKGROUNDCardiovascular disease is the most common cause of morbidity and mortality in kidney transplant recipients. Screening for coronary disease is frequently required prior to kidney transplantation, but coronary intervention has not been shown to be beneficial except in complex coronary artery disease. The likelihood of finding significant coronary artery disease and the benefits of routine pre-transplant screening are uncertain.METHODSWe performed a systematic review and meta-analysis. Medline & Embase were searched to identify manuscripts published between 1998 and 2024 reporting the results of pre-transplant screening. The primary endpoints were the frequency of detecting significant coronary lesions for which there are AHA class 1 indications for revascularization: a) >50% left main stenosis; or b) multi-vessel disease with ejection fraction < 35% during pre-kidney transplant screening. Secondary endpoints included frequency of detecting multivessel disease, proximal left anterior descending artery (LAD) disease, and number of patients who underwent invasive coronary angiography. Meta-regression was used to explore outcome heterogeneity according to the presence of hypertension, diabetes, and age.RESULTSWe identified 1273 studies out of which 44 met eligibility criteria. The mean prevalence of class 1 indications was 2%, although the heterogeneity was high with estimates ranging from 0% to 17%. Estimated prevalence of proximal LAD disease was 2% and left main stenosis was 1%, whereas 10% of patients had multi-vessel coronary artery disease, and 35% were referred for invasive angiography. There was no evidence of significant heterogeneity according to sex of the population or prevalence of diabetes or hypertension.CONCLUSIONSIdentification of class I indications for revascularization during pre-transplant coronary screening was rare.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"279 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240897","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}