Journal of The American Society of Nephrology最新文献

{"title":"Muscle Wasting and Arteriovenous Fistula Nonmaturation in Kidney Failure.","authors":"Srinivasan Beddhu, Yan-Ting Shiu","doi":"10.1681/ASN.0000000683","DOIUrl":"https://doi.org/10.1681/ASN.0000000683","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730680","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":"Transcriptional Regulators YAP and TAZ Have Distinct Abilities to Compensate for One Another in Podocytes.","authors":"Lioba Ester, Eva Wiesner, He Chen, Michel Ventzke, Paul Diefenhardt, Amrei M Mandel, Francesca Fabretti, Paul T Brinkkoetter, Thomas Benzing, Sandra Habbig, Martin Kann, Inês Cabrita, Bernhard Schermer","doi":"10.1681/ASN.0000000689","DOIUrl":"https://doi.org/10.1681/ASN.0000000689","url":null,"abstract":"<p><strong>Background: </strong>Kidney function depends on the filtration of enormous volumes of plasma, exposing the filtration barrier to mechanical forces. Podocytes must adapt to these forces for the lifetime of an organism as they cannot self-renew. The molecular mechanisms of podocyte adaptation to mechanical stress remain unclear. YAP and TAZ are key mechanotransducers that relay mechanical stimuli to control transcription.</p><p><strong>Methods: </strong>We made use of podocyte-specific knockout mouse models for Yap (YAPpKO), Taz (TAZpKO), or both (YAPpKO/ TAZpKO) and analyzed single-nucleus RNA sequencing (snRNA-seq) data of isolated glomeruli to delineate the distinct and shared roles of YAP and TAZ in podocyte homeostasis.</p><p><strong>Results: </strong>Here, we found that YAP and TAZ have only partially overlapping functions and compensatory potential in podocytes in vivo. YAPpKO mice displayed podocyte damage and progressive kidney failure. In contrast, TAZpKO animals did not develop any overt disease, while the combined deletion of Yap and Taz caused a neonatal lethal phenotype. snRNA-seq analysis revealed that in both YAPpKO or TAZpKO mice, a subpopulation of podocytes showed a similar stress response driven by AP1, revealing a protective compensatory mechanism. However, TAZ failed to compensate sufficiently for the loss of YAP, resulting in dysregulation of Rho-GTPases and subsequently the actin cytoskeleton in diseased YAPpKO. Furthermore, we observed loss of ERBB4 expression exclusively in YAPpKO, underscoring the role of ERBB4-signaling as additional layer of YAP-specific regulation in maintaining podocyte survival.</p><p><strong>Conclusions: </strong>In summary, we identified common and distinct roles for the two transcriptional regulators in podocyte homeostasis. YAP and TAZ can compensate for the loss of the other in podocytes to preserve viability. Still, while YAP can entirely compensate for the loss of TAZ securing podocyte health, TAZ fails to maintain all the YAP-specific functions leading to podocyte injury.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730681","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":"Association between CKD and Kidney Stones: A Reliable Relationship?","authors":"Guanghao Zheng, Tao Zeng","doi":"10.1681/ASN.0000000678","DOIUrl":"https://doi.org/10.1681/ASN.0000000678","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730635","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: Association between CKD and Kidney Stones: A Reliable Relationship?","authors":"Le-Ting Zhou, Muthuvel Jayachandran, Nicholas B Larson, John C Lieske","doi":"10.1681/ASN.0000000679","DOIUrl":"https://doi.org/10.1681/ASN.0000000679","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730650","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":"Anticoagulation for Atrial Fibrillation in Kidney Failure: A Call to Arms.","authors":"An S De Vriese","doi":"10.1681/ASN.0000000682","DOIUrl":"https://doi.org/10.1681/ASN.0000000682","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692596","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":"Estimation of Proximal Tubular Function by Stimulation of Organic Anion and Cation Transporters.","authors":"Magdalena Madero, Ana Karen Fernández-Yepez, Aldo Arturo Reséndiz-Albor, José Alberto Rivera Chávez, Jesse C Seegmiller, Bernardo Rodriguez-Iturbe","doi":"10.1681/ASN.0000000686","DOIUrl":"https://doi.org/10.1681/ASN.0000000686","url":null,"abstract":"<p><strong>Background: </strong>Tubular pathophysiology plays a critical role in the progression of chronic kidney disease (CKD). Exogenous stimulation of proximal tubule organic anion (OAT) and cation (OCT) transporters may be used to evaluate their responses independently of glomerular filtration rate (GFR) and their relation with clearance of protein-bound solutes and other biomarkers of tubular function.</p><p><strong>Methods: </strong>A proof of principle study was conducted in nine healthy volunteers and 22 patients with CKD classified by their GFR in KDIGO stages. They were studied hourly during 4 hours with water-induced diuresis, after the ingestion of 5g of creatinine and intravenous injection of 1-1.5mg/kg of furosemide, as means to stimulate OCTs and OATs, respectively. GFR determination (iohexol urinary clearance) was done in hours 2 to 3 and 3 to 4 of the study. Indoxyl sulfate, pCresol sulfate and urinary biomarkers of tubular function were studied in the first hour.</p><p><strong>Results: </strong>GFR was stable during the study. Maximal values of tubular secretion of creatinine (TScr) and furosemide (TSfuro) were obtained in the first hour. The KDIGO categories of GFR were widely distributed throughout the range of tubular secretory responses. One-hour stimulated response of organic anion transporters was negatively correlated with serum levels of Indoxyl sulfate (r=-0.59, p=0.005) and pCresol sulfate (r=-0.59, p=0.004). Urinary epidermal growth factor, ammonium, alpha 1 microglobulin, and uromodulin correlated with the increment of TScr and TSfuro. The urinary excretion rate of creatinine in the first hour after the ingestion of 5g of creatinine was strongly correlated with the TScr (r=0.836, p<0.001).</p><p><strong>Conclusions: </strong>The functions of OATs and OCTs of the proximal tubule varied considerably between patients with similar GFRs and their impaired response was associated with retention of protein-bound uremic solutes and urine biomarkers of tubular dysfunction. The response of OCTs may be estimated by the urinary excretion of creatinine 1-hour after the ingestion of 5g of creatinine.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692545","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":"Glycemia Assessed by Continuous Glucose Monitoring among People Treated with Maintenance Dialysis.","authors":"Ian H de Boer, Lisa D Anderson, Nathaniel K Ashford, Ernest Ayers, Nisha Bansal, Yoshio N Hall, Irl B Hirsch, Andrew N Hoofnagle, Simon Hsu, Evelin Jones, Benjamin Lidgard, Christine P Limonte, Lori J Linke, Chris C Marnell, Laura Mayeda, Elizabeth McNamara, Rajnish Mehrotra, Anne Pesenson, Julie M Porter, Matthew B Rivara, Glenda V Roberts, Beth Shanaman, Subbulaxmi Trikudanathan, Suzanne Watnick, Katy G Wilkens, Leila R Zelnick","doi":"10.1681/ASN.0000000693","DOIUrl":"10.1681/ASN.0000000693","url":null,"abstract":"<p><strong>Background: </strong>Kidney failure and its treatments disrupt glucose homeostasis in ways that may promote both hyperglycemia and hypoglycemia. Continuous glucose monitoring (CGM) delineates detailed glycemic profiles, but published studies in kidney failure are limited to small, select groups. We aimed to characterize the spectrum of glycemia and its determinants in a large, diverse maintenance dialysis population.</p><p><strong>Methods: </strong>We conducted a prospective community-based cohort study of people treated with maintenance dialysis. Each participant wore a Dexcom G6 Pro CGM for approximately 10 days. Outcomes ascertained by CGM included mean blood glucose, time in range (TIR, 70-180 mg/dL), and hypoglycemia events (sustained <70 mg/dL).</p><p><strong>Results: </strong>We enrolled 420 demographically diverse participants, including 263 with diabetes (of whom 88 were untreated with glucose-lowering medications) and 157 without diabetes. Peritoneal dialysis was used by 55. Outcomes varied by diabetes status and dialysis modality. Among participants without diabetes, mean blood glucose was higher with peritoneal dialysis vs hemodialysis (141 vs 121 mg/dL, p<0.001). Among participants with untreated diabetes, mean blood glucose was 162 mg/dL, mean TIR 71%, and only 64% of participants attained TIR ≥70%, while mean hemoglobin A1c was 5.7%. Among participants with treated diabetes, mean blood glucose was 214 mg/dL, mean TIR 43%, and only 22% of participants attained TIR ≥70%, while mean hemoglobin A1c was 7.0%. 714 unique sustained hypoglycemia events were observed, with highest rates for participants without diabetes. In addition to diabetes and dialysis modality, age, dialysis vintage, insulin use, hemoglobin A1c, and serum albumin were significantly associated with mean blood glucose, hypoglycemia, or both.</p><p><strong>Conclusions: </strong>In maintenance dialysis, CGM frequently identifies both hyperglycemia and hypoglycemia that may not be clinically evident. In particular, hyperglycemia is common with peritoneal dialysis, patients with untreated diabetes maintain a diabetic glycemic profile, and patients with treated diabetes rarely meet contemporary CGM-based treatment targets.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674263","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":"Toward Assessment of Tubular Function in Kidney Disease.","authors":"Sebastian B Beckmann, Madonna Salib, Robert A Fenton, Ewout J Hoorn","doi":"10.1681/ASN.0000000705","DOIUrl":"https://doi.org/10.1681/ASN.0000000705","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663500","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":"Deficiency of GADD45α-R-Loop Pathway and Kidney Injury in Diabetic Nephropathy.","authors":"Xue Qi Li, Jia Xiu Zhang, Liang Li, Qin Yi Wu, Xiong Zhong Ruan, Pei Pei Chen, Kun Ling Ma","doi":"10.1681/ASN.0000000681","DOIUrl":"https://doi.org/10.1681/ASN.0000000681","url":null,"abstract":"<p><strong>Background: </strong>Diabetic nephropathy is a primary cause of kidney failure. Persistent hyperglycemia causes metabolic perturbations epigenetically dysregulating gene expression in renal cells, thereby leading to diabetic nephropathy pathogenesis. On analyzing the GEO database by using machine learning algorithms, our preliminary results demonstrated that growth arrest and DNA damage-inducible 45α (GADD45α) might serve as key regulators in diabetic nephropathy. Furthermore, emerging evidence has shown that R-loops, the three-stranded DNA-RNA structures, are crucial to gene expression during diabetic nephropathy. Therefore, this study aimed to investigate the role of GADD45α in diabetic nephropathy by modulating epigenetic alterations through interaction with R-loops.</p><p><strong>Methods: </strong>A diabetic mouse model was established by injecting streptozotocin intraperitoneally into mice. Kidney histology and biochemical markers were analyzed in wild-type, GADD45α knockout, and renal tubule-specific GADD45α-overexpressing mice. The GADD45α lentivirus was used to induce the overexpression of GADD45α in HK-2 cells, while high-glucose treatment was applied to verify the mechanisms in vitro.</p><p><strong>Results: </strong>GADD45α expression was reduced in kidneys of diabetic nephropathy, correlating with kidney dysfunction. GADD45α knockout worsened kidney injuries, while overexpression mitigated them. Mechanistically, GADD45α interacted with R-loops on the STEAP4 promoter, recruiting TET1 to activate STEAP4 transcription. Deficiency in the GADD45α-R-loop pathway exacerbated mitochondrial injury, disrupted lipid metabolism, and increased oxidative stress in diabetic nephropathy.</p><p><strong>Conclusions: </strong>Deficiency of GADD45α exacerbates diabetic nephropathy by interacting with R-loops and inhibiting STEAP4 promoter demethylation. Targeting the GADD45α-R-loop pathway offers therapeutic potential against diabetic nephropathy.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657604","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":"Clinical Trial End Points for Childhood CKD.","authors":"Louise Oni, Jennifer McKenzie, Svenja Seide, William E Smoyer, Howard Trachtman","doi":"10.1681/ASN.0000000701","DOIUrl":"https://doi.org/10.1681/ASN.0000000701","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630532","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}