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
{"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}
{"title":"Pathomechanisms of Antinephrin Antibody-Mediated Podocytopathy.","authors":"Carolin Eul, Britta George","doi":"10.1681/ASN.0000000882","DOIUrl":"https://doi.org/10.1681/ASN.0000000882","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239083","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":"Novel Role of Tryptophan Metabolic Pathway in Mediating Peroxisomal Dysfunction in High-Dose Voclosporin-Induced Acute Kidney Injury.","authors":"Prabhleen Singh","doi":"10.1681/asn.0000000883","DOIUrl":"https://doi.org/10.1681/asn.0000000883","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"106 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235857","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":"Ethical Challenges in International Trials.","authors":"Valerie A Luyckx, Maria M Guraiib","doi":"10.1681/ASN.0000000891","DOIUrl":"10.1681/ASN.0000000891","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015689","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":"Inflammation and Cyst Expansion in Polycystic Kidney Disease.","authors":"Vijayakumar R Kakade,Lloyd G Cantley","doi":"10.1681/asn.0000000879","DOIUrl":"https://doi.org/10.1681/asn.0000000879","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"56 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235858","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}
Raj D Pandya,Emily M Lackner,C Shan Xu,Christopher Zugates,Mariia Burdyniuk,Andrea Reyna-Neyra,Vraj D Pandya,Wei-Ping Li,Song Pang,Ora A Weisz,Michael J Caplan
{"title":"Illuminating Renal Proximal Tubule Architecture through High-Resolution Volume EM and Machine Learning Analysis.","authors":"Raj D Pandya,Emily M Lackner,C Shan Xu,Christopher Zugates,Mariia Burdyniuk,Andrea Reyna-Neyra,Vraj D Pandya,Wei-Ping Li,Song Pang,Ora A Weisz,Michael J Caplan","doi":"10.1681/asn.0000000884","DOIUrl":"https://doi.org/10.1681/asn.0000000884","url":null,"abstract":"BACKGROUNDKidney epithelial cells perform complex vectorial fluid and solute transport at high volumes and rapid rates. Their structural organization both reflects and enables these sophisticated physiological functions. However, our understanding of the nanoscale spatial organization and intracellular ultrastructure that underlies these crucial cellular functions remains limited.METHODSTo address this knowledge gap, we generated and reconstructed an extensive electron microscopic dataset of renal proximal tubule (PT) epithelial cells at isotropic resolutions down to 4nm. We employed artificial intelligence-based segmentation tools to identify, trace, and measure all major subcellular components. We complemented this analysis with immunofluorescence microscopy to connect subcellular architecture to biochemical function.RESULTSOur ultrastructural analysis revealed complex organization of membrane-bound compartments in proximal tubule cells. The apical endocytic system featured deep invaginations connected to an anastomosing meshwork of dense apical tubules, rather than discrete structures. The endoplasmic reticulum displayed distinct structural domains: fenestrated sheets in the basolateral region and smaller, disconnected clusters in the subapical region. We identified, quantified, and visualized membrane contact sites between endoplasmic reticulum, plasma membrane, mitochondria, and apical endocytic compartments. Immunofluorescence microscopy demonstrated distinct localization patterns for endoplasmic reticulum resident proteins at mitochondrial and plasma membrane interfaces.CONCLUSIONSThis study provides novel insights into proximal tubule cell organization, revealing specialized compartmentalization and unexpected connections between membrane-bound organelles. We identified previously uncharacterized structures, including mitochondria-plasma membrane bridges and an interconnected endocytic meshwork, suggesting mechanisms for efficient energy distribution, cargo processing and structural support. Morphological differences between 4nm and 8nm datasets indicate subsegment-specific specializations within the proximal tubule. This comprehensive open-source dataset provides a foundation for understanding how subcellular architecture supports specialized epithelial function in health and disease.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"16 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235859","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}
Yu Feng,Yanmiao Qi,Yang Yang,Stephen I Alexander,Yin Xia,Xiangjian Zheng
{"title":"Hmx2 and Dmrt2 Coordinate the Differentiation of Intercalated Cell Subtypes in Kidney.","authors":"Yu Feng,Yanmiao Qi,Yang Yang,Stephen I Alexander,Yin Xia,Xiangjian Zheng","doi":"10.1681/asn.0000000885","DOIUrl":"https://doi.org/10.1681/asn.0000000885","url":null,"abstract":"BACKGROUNDIntercalated cells in the kidney collecting ducts are essential for maintaining systemic acid-base homeostasis. Based on gene expression profiles and functional characteristics, intercalated cells are classified into type A, type B, non-A/non-B. While several transcription factors have been reported to regulate intercalated cells differentiation, how the fates of intercalated cell subtypes are established remains unclear.METHODSTo investigate the roles of Dmrt2 and Hmx2 in intercalated cell subtype differentiation, we generated mice with single or double conditional deletion and knock-in of these transcription factors specifically in distal nephron segments and analyzed their effects on urine acidification. We also performed single-cell RNA sequencing analysis on mouse and human kidney datasets to trace intercalated cell progenitor fate trajectories.RESULTSLoss of Hmx2 in the distal nephron prevented type-B intercalated cell differentiation, whereas simultaneous deletion of Hmx2 and Dmrt2 compromised type-A intercalated cell differentiation, with a concomitant increase in Hmx3 expression and type-B intercalated cell differentiation. Dmrt2 knock-in mice exhibited a modest increase in type-A intercalated cell differentiation and a marked reduction in type-B intercalated cells. Notably, Dmrt2 knockin did not rescue the intercalated cell differentiation defects observed in Foxp1 deficient mice. Analysis of mouse and human single cell RNA sequencing data further confirmed the mutually exclusive expression patterns of Hmx2 and Dmrt2 in the kidney.CONCLUSIONSHmx2 and Dmrt2 were essential, mutually exclusive transcription factors that govern intercalated cell subtype differentiation in the kidney, with Hmx2 specifying type-B intercalated cell fate and Dmrt2 promoting type-A intercalated cell differentiation. Dmrt2 supressed the expression of Hmx2 and Hmx3. In the absence of Dmrt2 and Hmx2, Hmx3 expression was activated to promote type-B intercalated cell differentiation.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"21 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235860","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":"N-of-1 Trials in Nephrology: Moving beyond Case Series.","authors":"Joyce P Samuel","doi":"10.1681/asn.0000000906","DOIUrl":"https://doi.org/10.1681/asn.0000000906","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"348 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235862","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}
Augusto Cama-Olivares, Chloe Braun, Tomonori Takeuchi, Emma C O'Hagan, Kathryn A Kaiser, Lama Ghazi, Jin Chen, Lui G Forni, Sandra L Kane-Gill, Marlies Ostermann, Benjamin Shickel, Jacob Ninan, Javier A Neyra
{"title":"Systematic Review and Meta-Analysis of Machine Learning Models for Acute Kidney Injury Risk Classification.","authors":"Augusto Cama-Olivares, Chloe Braun, Tomonori Takeuchi, Emma C O'Hagan, Kathryn A Kaiser, Lama Ghazi, Jin Chen, Lui G Forni, Sandra L Kane-Gill, Marlies Ostermann, Benjamin Shickel, Jacob Ninan, Javier A Neyra","doi":"10.1681/ASN.0000000702","DOIUrl":"10.1681/ASN.0000000702","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1969-1983"},"PeriodicalIF":9.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12499627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735996","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}
Hwang Chan Yu, Byeoung Hoon Chung, Yoejin Kim, Yoonji Lee, Hyunchae Sim, Sangkyu Lee, Hong Pil Hwang, Hee Chul Yu, Seunggyu Jeon, Han-Joo Maeng, Dongyun Shin, Kyung Pyo Kang, Seung-Yong Seo, Eun Ju Bae, Byung-Hyun Park
{"title":"Correction to: p21-Activated Kinase 4 and Ischemic Acute Kidney Injury in Mice and Humans.","authors":"Hwang Chan Yu, Byeoung Hoon Chung, Yoejin Kim, Yoonji Lee, Hyunchae Sim, Sangkyu Lee, Hong Pil Hwang, Hee Chul Yu, Seunggyu Jeon, Han-Joo Maeng, Dongyun Shin, Kyung Pyo Kang, Seung-Yong Seo, Eun Ju Bae, Byung-Hyun Park","doi":"10.1681/ASN.0000000818","DOIUrl":"10.1681/ASN.0000000818","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"2085-2088"},"PeriodicalIF":9.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12499618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144612188","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}