Journal of The American Society of Nephrology最新文献

{"title":"LAPTM5: A Novel Target in an Old Fight against Tubular Senescence.","authors":"Michael S Balzer","doi":"10.1681/ASN.0000000524","DOIUrl":"https://doi.org/10.1681/ASN.0000000524","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546152","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 Association of Outdoor Temperature with Severe Hyponatremia: A Study Based on the Stockholm Sodium Cohort.","authors":"Issa Issa,Jakob Skov,Henrik Falhammar,Jonatan Lindh,Buster Mannheimer","doi":"10.1681/asn.0000000519","DOIUrl":"https://doi.org/10.1681/asn.0000000519","url":null,"abstract":"BACKGROUNDHyponatremia is a common condition with unspecific symptoms and a complicated etiology. The impact of outdoor temperature on hyponatremia is not well-studied and varies depending on the climate and location. This study aimed to investigate the association between outdoor temperature and the prevalence of severe hyponatremia.METHODSThis retrospective register-based cohort study based on the Stockholm Sodium Cohort investigated the association between ambient temperatures and severe hyponatremia (<125 mmol/L) in adults. Prevalence rates of severe hyponatremia were calculated as the number of days of severe hyponatremia divided by person-days at risk for the same temperature, using mean daily temperatures at the area of residence of each study participant to calculate exposure time. A prediction model incorporating changes in demographics and climate was used to estimate the burden of severe hyponatremia in Stockholm by 2050.RESULTSWe identified 51,143 episodes of severe hyponatremia in 21,924 adults. A near linear modest increase in prevalence with rising temperatures was observed up to 20°C, followed by rapidly increasing rates at higher temperatures. The prevalence was higher with older age, reaching >100 days of hyponatremia per million person-days among +80-years-olds at temperatures over 22°C. Women experienced twice the rate observed in men. Temperature rises of 1°C or 2°C by the year 2050 are expected to be associated with higher prevalence rates by 66% and 73%, respectively.CONCLUSIONSThere was a strong association between high temperatures and severe hyponatremia. The higher prevalence of severe hyponatremia was most pronounced among elderly.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"8 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439360","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":"Circadian Clock Disruption and Growth of Kidney Cysts in Autosomal Dominant Polycystic Kidney Disease.","authors":"Abeda Jamadar, Christopher J Ward, Viji Remadevi, Meekha M Varghese, Navjot S Pabla, Michelle L Gumz, Reena Rao","doi":"10.1681/ASN.0000000528","DOIUrl":"10.1681/ASN.0000000528","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468645","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":"Premature Conclusion that Sodium-Glucose Cotransporter-2 Inhibitors Improve Kidney Outcomes in Patients with Heart Failure.","authors":"Fan Zhang,Xianwen Zhang,Yifei Zhong","doi":"10.1681/asn.0000000527","DOIUrl":"https://doi.org/10.1681/asn.0000000527","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"17 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439239","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":"Safety and Efficacy of Avacopan in Patients with C3 Glomerulopathy: Randomized, Double-Blind Clinical Trial.","authors":"Andrew S Bomback, Leal C Herlitz, Priyanka Punit Kedia, Jeffrey Petersen, Huibin Yue, Richard A Lafayette","doi":"10.1681/ASN.0000000526","DOIUrl":"https://doi.org/10.1681/ASN.0000000526","url":null,"abstract":"<p><strong>Background: </strong>Complement 3 (C3) glomerulopathy is a rare autoimmune disorder characterized by activation of the alternative complement pathway with isolated or dominant C3 deposition in glomeruli. Patients with C3 glomerulopathy may develop progressive deterioration in kidney function and kidney failure.</p><p><strong>Methods: </strong>We studied the safety and efficacy of avacopan 30 mg twice daily in patients with C3 glomerulopathy (N=57) with elevated (> 244 ng/mL) and normal (≤ 244 ng/mL) levels of C5b-9 in a randomized, double-blind, placebo-controlled, phase 2 trial, with kidney biopsies performed pre-randomization and at 26 and 52 weeks. The primary outcome was the percent change from baseline to week 26 in C3 glomerulopathy histologic index for disease activity.</p><p><strong>Results: </strong>The study was conducted in patients with C3 glomerulopathy, including C3 glomerulonephritis and DDD. The median study duration was 60.0 weeks (interquartile range 59.9 to 61.0). There were no significant differences in the primary outcome between the avacopan and the placebo group; least square mean treatment difference (95% CI) = -0.0 (-1.9 to 1.8). The secondary measures of efficacy including C3 Glomerulopathy Histological Index for disease chronicity, urine protein:creatinine ratio (UPCR), and estimated glomerular filtration rate (eGFR) were not different between treatment groups. The overall incidence and type of adverse events for both treatment groups were comparable. No deaths were reported during the study, and no new safety signals were detected.</p><p><strong>Conclusions: </strong>The primary end point for the study was not met; other clinical effects of avacopan to improve certain key kidney function parameters and slow disease progression were variable and require further evaluation.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406561","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":"Urinary Cytokeratin 20 as a Biomarker for AKI-CKD Transition among Patients with Acute Decompensated Heart Failure and Acute Kidney Injury.","authors":"Han Ouyang, Rui Ma, Xiaobing Yang, Chunbo Chen, Xin Xu, Jianwei Tian, Jun Liu, Yan Zha, Huafeng Liu, Tiecheng Yang, Fan Fan Hou","doi":"10.1681/ASN.0000000518","DOIUrl":"10.1681/ASN.0000000518","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502833","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":"Targeting KLF2 as a Novel Therapy for Glomerular Endothelial Cell Injury in Diabetic Kidney Disease.","authors":"Lulin Min, Yixin Chen, Ruijie Liu, Zhengzhe Li, Leyi Gu, Sandeep Mallipattu, Bhaskar Das, Kyung Lee, John Cijiang He, Fang Zhong","doi":"10.1681/ASN.0000000000000498","DOIUrl":"10.1681/ASN.0000000000000498","url":null,"abstract":"<p><strong>Background: </strong>DKD is a microvascular disease, and glomerular endothelial cell injury is a key pathological event in DKD development. Through unbiased screening of glomerular transcriptomes, we previously identified KLF2 as a highly regulated gene in diabetic kidneys. KLF2 exhibits protective effects in endothelial cells by inhibiting inflammation, thrombotic activation, and angiogenesis, all of which are protective for cardiovascular disease. We previously demonstrated that endothelial cell-specific ablation of Klf2 exacerbated diabetes-induced glomerular endothelial cell injury and DKD in mice. Therefore in this study, we sought to assess the therapeutic potential of KLF2 activation in murine models of DKD.</p><p><strong>Methods: </strong>We first examined the effects of endothelial cell-specific inducible overexpression of KLF2 (KLF2ov) in streptozotocin-induced diabetic mice. We developed small molecule KLF2 activators and tested whether increased KLF2 activity could impede DKD progression in type 2 diabetic db/db and BTBR ob/ob mice.</p><p><strong>Results: </strong>Diabetic KLF2ov mice had attenuated albuminuria, glomerular endothelial cell injury, and diabetic glomerulopathy compared to control diabetic mice. Novel KLF2 activator, compound 6 (C-6) effectively induced downstream Nos3 expression and suppressed NF-kB activation in glomerular endothelial cells. The administration of C-6 improved albuminuria and glomerulopathy in db/db and BTBR ob/ob mice, which was associated with improved glomerular endothelial cell and podocyte injury.</p><p><strong>Conclusions: </strong>These results validate KLF2 as a potential drug target and KLF2 activators such as C-6 as a novel therapy for DKD.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391499","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":"Self-Supervised Learning for Feature Extraction from Glomerular Images and Disease Classification with Minimal Annotations.","authors":"Masatoshi Abe, Hirohiko Niioka, Ayumi Matsumoto, Yusuke Katsuma, Atsuhiro Imai, Hiroki Okushima, Shingo Ozaki, Naohiko Fujii, Kazumasa Oka, Yusuke Sakaguchi, Kazunori Inoue, Yoshitaka Isaka, Isao Matsui","doi":"10.1681/ASN.0000000514","DOIUrl":"https://doi.org/10.1681/ASN.0000000514","url":null,"abstract":"<p><strong>Background: </strong>Deep learning has great potential in digital kidney pathology. However, its effectiveness depends heavily on the availability of extensively labeled datasets, which are often limited due to the specialized knowledge and time required for their creation. This limitation hinders the widespread application of deep learning for the analysis of kidney biopsy images.</p><p><strong>Methods: </strong>We applied self-distillation with no labels (DINO), a self-supervised learning method, to a dataset of 10,423 glomerular images obtained from 384 PAS-stained kidney biopsy slides. Glomerular features extracted from the DINO-pretrained backbone were visualized using principal component analysis (PCA). We then performed classification tasks by adding either k-nearest neighbor (kNN) classifiers or linear head layers to the DINO-pretrained or ImageNet-pretrained backbones. These models were trained on our labeled classification dataset. Performance was evaluated using metrics such as the area under the receiver operating characteristic curve (ROC-AUC). The classification tasks encompassed four disease categories (minimal change disease, mesangial proliferative glomerulonephritis, membranous nephropathy, and diabetic nephropathy) as well as clinical parameters such as hypertension, proteinuria, and hematuria.</p><p><strong>Results: </strong>PCA visualization revealed distinct principal components corresponding to different glomerular structures, demonstrating the capability of the DINO-pretrained backbone to capture morphological features. In disease classification, the DINO-pretrained transferred model (ROC-AUC = 0.93) outperformed the ImageNet-pretrained fine-tuned model (ROC-AUC = 0.89). When the labeled data were limited, the ImageNet-pretrained fine-tuned model's ROC-AUC dropped to 0.76 (95% confidence interval [CI], 0.72-0.80), whereas the DINO-pretrained transferred model maintained superior performance (ROC-AUC 0.88, 95% CI 0.86-0.90). The DINO-pretrained transferred model also exhibited higher AUCs for the classification of several clinical parameters. External validation using two independent datasets confirmed DINO pre-training's superiority, particularly when labeled data were limited.</p><p><strong>Conclusions: </strong>The application of DINO to unlabeled PAS-stained glomerular images facilitated the extraction of histological features that can be effectively utilized for disease classification.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391498","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":"Autoantibodies Targeting Proteasome Subunit Alpha Type 1 in Autoimmune Podocytopathies.","authors":"Huihui Liu, Chao Zhou, Dongjie Wang, Hanyan Meng, Shifan Zhu, Jiayu Zhang, Jianhua Mao, Qing Ye","doi":"10.1681/ASN.0000000525","DOIUrl":"https://doi.org/10.1681/ASN.0000000525","url":null,"abstract":"<p><strong>Background: </strong>The antibody against proteasome subunit alpha type 1 (PSMA1) is a podocyte autoantibody in idiopathic nephrotic syndrome (INS) children identified in our previous study. The aim of this study was to explore the characteristics of INS in children and the mechanism underlying its involvement in the development of INS.</p><p><strong>Methods: </strong>The levels of serum anti-PSMA1 autoantibodies in children were detected via protein microarray and compared among different disease groups. The recombinant PSMA1 protein was injected subcutaneously and intraperitoneally into mice to observe glomerular morphology and function. The PSMA1-knockdown and PSMA1-overexpressing cell lines were constructed from mouse podocytes, and their cytoskeleton and function were analyzed. Homozygous zebrafish with psma1 knockout were observed.</p><p><strong>Results: </strong>The levels of serum anti-PSMA1 autoantibodies were higher in INS children and varied with urinary protein. In mice immunized with PSMA1, the presence of serum anti-PSMA1 autoantibody caused albuminuria and damage to the glomerular filtration membrane. Deficiency of PSMA1 impaired the podocyte cytoskeleton and physiological function. Complete deletion of psma1 caused edema, abnormal glomerular morphology and effacement of foot processes in zebrafish.</p><p><strong>Conclusions: </strong>PSMA1 played an important role in the maintenance of podocyte morphology and function.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391497","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":"Acetazolamide Therapy and Kidney Function in Persons with Nonalbuminuric Diabetes Mellitus Type 1.","authors":"Charles Ginsberg, Jesse C Seegmiller, Volker Vallon, Sami SeungMi Jin, Robert L Thomas, Schafer C Boeder, Jeremy Pettus, Joachim H Ix","doi":"10.1681/ASN.0000000515","DOIUrl":"10.1681/ASN.0000000515","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502828","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}