{"title":"Isoaspartate Repair of TGF-β Receptor 2: A Novel Checkpoint in Kidney Fibrosis.","authors":"Christoph Kuppe","doi":"10.1681/ASN.0000000757","DOIUrl":"10.1681/ASN.0000000757","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225826","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}
Madhumitha Rajagopal, Justin Kauffman, Girish N Nadkarni
{"title":"Geometric Deep Learning for Multimodal Data in CKD.","authors":"Madhumitha Rajagopal, Justin Kauffman, Girish N Nadkarni","doi":"10.1681/ASN.0000000778","DOIUrl":"https://doi.org/10.1681/ASN.0000000778","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216184","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":"Cdc42 Activation in Anti-nephrin Antibody-Induced Nephropathy.","authors":"Ying Zhang, Yoshiyasu Fukusumi, Hidenori Yasuda, Guoqing Chang, Mutsumi Kayaba, Hiroshi Kawachi","doi":"10.1681/ASN.0000000728","DOIUrl":"https://doi.org/10.1681/ASN.0000000728","url":null,"abstract":"<p><strong>Background: </strong>A subset of minimal change nephrotic syndrome was reported to be induced by autoantibodies against nephrin. We have reported that rats injected with murine anti-nephrin antibody showed proteinuria. However, its precise pathogenic mechanisms remain unclear.</p><p><strong>Methods: </strong>The initiation events of podocyte disturbance caused by anti-nephrin antibodies were analyzed using an in vivo rat model and in vitro assays with rat isolated glomeruli and human cultured podocytes. To elucidate the role of ephrin-B1 at the slit diaphragm, podocyte-specific ephrin-B1 knockout mice were analyzed.</p><p><strong>Results: </strong>Nephrin-binding ephrin-B1 at slit diaphragm interacted with Par6 and interfered with the binding of Par6 with cdc42. Anti-nephrin antibodies caused the phosphorylations of nephrin and ephrin-B1 in a TRPC6-mediated Ca2+ influx-dependent manner. Phosphorylated ephrin-B1 was dissociated from nephrin and also from Par6. Par6, released by ephrin-B1, interacted with cdc42. The binding of Par6 stabilized cdc42 and consequently promoted cdc42 activity. Elevated cdc42 activity increased calcineurin activity and consequently activated Snail. The activated Snail negatively regulated the mRNA expressions of the slit diaphragm functional molecules, nephrin and ephrin-B1. Elevated cdc42 activity activated Stat3 independently of calcineurin. The activated Stat3 brought on the expression of claudin1, a tight junction molecule. The altered expressions of these molecules at the protein level were observed in the rat anti-nephrin antibody-induced nephropathy when the rats showed proteinuria.</p><p><strong>Conclusions: </strong>Ephrin-B1 at slit diaphragm suppresses cdc42 activity by preventing the interaction of Par6 with cdc42 and functions to keep the specialized phenotype of podocytes. Elevated cdc42 activity induced by the binding of Par6, released by the phosphorylated ephrin-B1, is a critical initiation event leading to proteinuria in the anti-nephrin antibody-induced nephropathy.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216183","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}
Zhang Li, Raksha P Hombal, Jun Wang, Sreelakshmi Cherakara, Timothy C Howton, Kurt A Zimmerman, James F Collawn, Reagan S Andersen, Courtney J Haycraft, Mandy J Croyle, John M Parant, Brittany N Lasseigne, Bradley K Yoder
{"title":"Macrophage Accumulation and Cyst Expansion in Pkd2, Ift88, and Double Mutant Mouse Models.","authors":"Zhang Li, Raksha P Hombal, Jun Wang, Sreelakshmi Cherakara, Timothy C Howton, Kurt A Zimmerman, James F Collawn, Reagan S Andersen, Courtney J Haycraft, Mandy J Croyle, John M Parant, Brittany N Lasseigne, Bradley K Yoder","doi":"10.1681/ASN.0000000746","DOIUrl":"https://doi.org/10.1681/ASN.0000000746","url":null,"abstract":"<p><strong>Background: </strong>Kidney cyst formation occurs due to loss of cilia localized polycystin proteins (e.g., Pkd1 or Pkd2) or ciliary structure (e.g., Ift88 or Kif3a). However, cyst progression is more rapid in polycystin mutant mice compared to cilia mutant mice, and loss of cilia in the polycystin mutant background (e.g., Pkd2 and Kif3a mutation) greatly attenuates cyst development. This led to the proposal that the polycystins function to repress a cyst promoting pathway that is dependent on an intact cilium, this is referred to as the Cilia-Dependent Cyst Activating (CDCA) pathway. Renal macrophages are also involved in regulating cyst progression, but it is unknown whether this occurs through the CDCA or separate pathway.</p><p><strong>Methods: </strong>To examine whether macrophage accumulation was regulated through a cilia-dependent pathway, we compared macrophage accumulation and cytokine expression levels in Pkd2 mutant kidneys with or without intact cilia (Ift88 mutants). To avoid the impact of cyst induced damage on macrophage accumulation, we conducted comparisons after standardizing the samples for cystic indices between the Pkd2, Ift88, and Pkd2;Ift88 double mutants.</p><p><strong>Results: </strong>Disruption of Ift88 in Pkd2 mutants reduced cyst burden and attenuated macrophage accumulation and cytokine expression levels. However, when the mutants were standardized based on cystic indices, no significant differences in macrophage number or cytokine expression were evident between the Pkd2, Ift88, and Pkd2;Ift88 double mutants at either early or advanced stage of cyst progression and pathway analysis revealed the macrophage populations were similar between groups based on single-cell RNAseq data.</p><p><strong>Conclusions: </strong>These data indicated that macrophage accumulation and cytokine expression did not drive cyst initiation but rather paralleled cyst expansion regardless of the genotype or rate of disease progression through a cilia independent pathway.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208858","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}
McKenzie Zellers, Kaushal Solanki, Melissa A Kelly, Karyn M Murphy, Kyle Retterer, H Lester Kirchner, Ion Dan Bucaloiu, Bryn Moore, Tooraj Mirshahi, Alexander R Chang
{"title":"Genotype-First Analysis in an Unselected Health System-Based Population and Phenotypic Severity of COL4A5 Variants.","authors":"McKenzie Zellers, Kaushal Solanki, Melissa A Kelly, Karyn M Murphy, Kyle Retterer, H Lester Kirchner, Ion Dan Bucaloiu, Bryn Moore, Tooraj Mirshahi, Alexander R Chang","doi":"10.1681/ASN.0000000580","DOIUrl":"10.1681/ASN.0000000580","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1138-1151"},"PeriodicalIF":10.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770104","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}
Benjamin Lazarus, Simon J Davies, Kevan R Polkinghorne
{"title":"Volume Assessment in Patients Undergoing Long-Term Dialysis.","authors":"Benjamin Lazarus, Simon J Davies, Kevan R Polkinghorne","doi":"10.1681/ASN.0000000724","DOIUrl":"10.1681/ASN.0000000724","url":null,"abstract":"<p><p>Accurate assessment of fluid status is a priority for patients with kidney failure undergoing long-term dialysis. There is wide variation in current volume-related practices between dialysis units and an urgent need to develop better evidence to guide practice. Clinical decisions relating to volume management are implicitly based on assessment of volume status, and there are numerous different but imperfect methods of assessment. Isotope-based dilutions are impractical for clinical use and may not be a gold standard for patients with kidney failure. Individual trends in body weight and BP have been used as a pragmatic surrogate marker for volume status. Probing the target weight based on BP is still widely practiced but may pose risks related to volume depletion and accelerated loss of residual kidney function. Clinical signs, such as elevated jugular venous pressure and leg edema, are readily accessible but have poor diagnostic accuracy and wide interobserver variability that limit their reproducibility for volume assessment in clinical trials. Lung ultrasound and bioelectrical impedance analysis have a sound scientific rationale for the assessment of extracellular volume and are appropriately associated with clinical outcomes, but neither approach has demonstrated convincingly favorable clinical outcomes in clinical trials. Other technologies for volume assessment exist but require further assessment in clinical trials. Advancements in clinical care can be made with existing technologies through comparative effectiveness trials of different fluid management strategies, routine and standardized measurement of volumetric parameters and individual patient preferences, and innovative integration of existing volume assessment methods. A systematic and globally coordinated approach to improving volume assessment and management is required to improve outcomes in patients receiving long-term dialysis.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1184-1196"},"PeriodicalIF":10.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795947","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}
Nina Himmerkus, Catarina Quintanova, Harneet Bhullar, Wouter H van Megen, Amanda Lima Deluque, Karsten Skjødt, Milos Bogdanovic, Markus Bleich, R Todd Alexander, Henrik Dimke
{"title":"Calcium-Sensing Receptor in the Thick Ascending Limb and Renal Response to Hypercalcemia.","authors":"Nina Himmerkus, Catarina Quintanova, Harneet Bhullar, Wouter H van Megen, Amanda Lima Deluque, Karsten Skjødt, Milos Bogdanovic, Markus Bleich, R Todd Alexander, Henrik Dimke","doi":"10.1681/ASN.0000000612","DOIUrl":"10.1681/ASN.0000000612","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1028-1039"},"PeriodicalIF":10.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007455","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}
Ning Shi, Ji-Wen Wang, Gengchen Su, Gaoxiang Ma, Feng-Qing Huang, Si-Jia Jin, Hua-Mei Xie, Wen-Xin Ge, Jiang-Ping Song, Xiaodong Luan, Lei Zhang, Lian-Wen Qi
{"title":"N -Acetyl-Tryptophan in Acute Kidney Injury after Cardiac Surgery.","authors":"Ning Shi, Ji-Wen Wang, Gengchen Su, Gaoxiang Ma, Feng-Qing Huang, Si-Jia Jin, Hua-Mei Xie, Wen-Xin Ge, Jiang-Ping Song, Xiaodong Luan, Lei Zhang, Lian-Wen Qi","doi":"10.1681/ASN.0000000626","DOIUrl":"10.1681/ASN.0000000626","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1040-1055"},"PeriodicalIF":10.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023941","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}
Gabriela Accetta Rojas, Charles E McCulloch, Timothy P Copeland, Adrian M Whelan, Alexandra C Bicki, Sophia Giang, Barbara A Grimes, Elaine Ku
{"title":"Pediatric Nephrology Workforce and Access of Children with Kidney Failure to Transplantation in the United States.","authors":"Gabriela Accetta Rojas, Charles E McCulloch, Timothy P Copeland, Adrian M Whelan, Alexandra C Bicki, Sophia Giang, Barbara A Grimes, Elaine Ku","doi":"10.1681/ASN.0000000586","DOIUrl":"10.1681/ASN.0000000586","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1164-1172"},"PeriodicalIF":10.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142789600","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}
Jordan B Strom, Brandon M Herbert, Marnie Bertolet, Maria M Brooks, Shahbaz A Malik, Gilles Lemesle, Mina Madan, Philippe Gabriel Steg, Paul C Hebert, Jay H Traverse, Harvey D White, Caroline Alsweiler, Rajesh Gupta, Luiz Eduardo F Ritt, Mark A Menegus, John H Alexander, Renato D Lopes, Bernard R Chaitman, Jeffrey L Carson
{"title":"Restrictive or Liberal Blood Transfusion in Patients with Myocardial Infarction and CKD.","authors":"Jordan B Strom, Brandon M Herbert, Marnie Bertolet, Maria M Brooks, Shahbaz A Malik, Gilles Lemesle, Mina Madan, Philippe Gabriel Steg, Paul C Hebert, Jay H Traverse, Harvey D White, Caroline Alsweiler, Rajesh Gupta, Luiz Eduardo F Ritt, Mark A Menegus, John H Alexander, Renato D Lopes, Bernard R Chaitman, Jeffrey L Carson","doi":"10.1681/ASN.0000000595","DOIUrl":"10.1681/ASN.0000000595","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1116-1125"},"PeriodicalIF":10.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950721","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}