Journal of The American Society of Nephrology最新文献

{"title":"What Are Baskets, Umbrellas, and Platforms Doing in Nephrology Clinical Trials?","authors":"Julie Lin, Jai Radhakrishnan","doi":"10.1681/ASN.0000000648","DOIUrl":"10.1681/ASN.0000000648","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123089","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":"Characterization of the Cystic Phenotype Associated with Monoallelic ALG8 and ALG9 Pathogenic Variants.","authors":"Tabinda Jawaid, Doaa E Elbarougy, Sravanthi Lavu, Guillaume Buia, Sarah R Senum, Eric Olinger, Hana Yang, Shannon K McDonnell, Joshua T Bublitz, Jun Ma, Marie-Pierre Audrézet, Charles D Madsen, Rachel S Schauer, Tracy A Baker, Adriana V Gregory, Sarah G Orr, Miguel Barroso-Gil, Ruxandra Neatu, Giancarlo Joli, Neera K Dahl, Timothy L Kline, Valentine Gillion, Karin Dahan, Francois Jouret, Ronald D Perrone, Theodore I Steinman, Dorien J M Peters, Berenice Y Gitomer, Terry J Watnick, Eliecer Coto, Fouad T Chebib, Marie C Hogan, Janet E Olson, Nicholas B Larson, Elisabet Ars, Jan Halbritter, Nathalie Demoulin, Vicente E Torres, John A Sayer, Emilie Cornec-Le Gall, Peter C Harris","doi":"10.1681/ASN.0000000613","DOIUrl":"10.1681/ASN.0000000613","url":null,"abstract":"<p><strong>Background: </strong>Autosomal dominant polycystic kidney disease (ADPKD) is a common, inherited nephropathy often resulting in kidney failure. It is genetically heterogeneous; along with the major genes, PKD1 and PKD2, at least 8 others have been suggested. ALG8 pathogenic variants have been associated with autosomal dominant polycystic liver disease and implicated in ADPKD, while ALG9 has been suggested as an ADPKD gene, but details of the phenotypes and penetrance are unclear.</p><p><strong>Methods: </strong>We screened >3900 families with cystic kidneys and/or livers using global approaches to detect ALG8 or ALG9 pathogenic variants. In addition, population cohorts with sequence data (Genomics England 100kGP (100kGP), UK Biobank (UKBB), and Mayo Clinic Biobank (MCBB)), were screened for ALG8/ALG9 pathogenic variants.</p><p><strong>Results: </strong>Multicenter screening of individuals with polycystic kidney and/or liver disease identified 51 (1.3%) ALG8 (7 multiplex) and 23 (0.6%) ALG9 (5 multiplex) families; frequencies that were ∼10x and ∼24x greater than non-polycystic kidney disease (PKD) controls. Analysis of individuals with PKD phenotypes in 100kGP, UKBB, and MCBB identified 9 ALG8 (0.39%) and 9 ALG9 (0.39%) families, an enriched frequency over controls. Two individuals had PKD1 and ALG8 pathogenic changes. Eighty-nine percent of individuals with ALG8 mutations with imaging in the entire MCBB had kidney cysts (56%, >10 cysts), with greater median kidney and liver cyst numbers than controls. For ALG9, 78% had kidney cysts (27%, >10 cysts). Individuals with ALG8 mutations typically had mild cystic kidneys with limited enlargement. Liver cysts were common (71%) with enlarged livers (>2L) found in 11/62 patients although surgical intervention was rare. The ALG9 kidney phenotype was also of mild cystic kidneys but enlarged livers were rare; for both genes chronic kidney disease or kidney failure were rare.</p><p><strong>Conclusions: </strong>ALG8 and ALG9 are defined as cystic kidney/liver genes but with limited penetrance for lower eGFR.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123087","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":"Genotype-Based Molecular Mechanisms in Alport Syndrome.","authors":"Emine Bilge Caparali, Vanessa De Gregorio, Moumita Barua","doi":"10.1681/ASN.0000000647","DOIUrl":"10.1681/ASN.0000000647","url":null,"abstract":"<p><p>Alport syndrome is an inherited disorder characterized by kidney disease, sensorineural hearing loss, and ocular abnormalities. Alport syndrome is caused by pathogenic variants in COL4A3 , COL4A4 , or COL4A5 , which encode the α 3, α 4, and α 5 chains of type 4 collagen that forms a heterotrimer expressed in the glomerular basement membrane. Knowledge of its genetic basis has informed the development of different models in dogs, mice, and rats that reflect its autosomal and X-linked inheritance patterns as well as different mutation types, including protein-truncating and missense variants. A key difference between these two types is the synthesis of α 3 α 4 α 5(IV), which is not made in autosomal Alport syndrome (two pathogenic variants in trans or biallelic) or male patients with X-linked Alport syndrome due to protein-truncating variants. By contrast, α 3 α 4 α 5(IV) is synthesized in Alport syndrome because of missense variants. For missense variants, in vitro studies suggest that these cause impaired type 4 collagen trafficking and endoplasmic reticulum stress. For protein-truncating variants, knockout models suggest that persistence of an immature α 1 α 1 α 2(IV) network is associated with biomechanical strain, which activates endothelin-A receptors leading to mesangial filopodia formation. Moreover, studies suggest that activation of collagen receptors, integrins and discoidin domain receptor 1, play a role in disease propagation. In this review, we provide an overview of how these genotype-phenotype mechanisms are key for a precision medicine-based approach in the future.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123088","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":"Harnessing Evolution and Biomimetics to Enhance Planetary Health: Kidney Insights.","authors":"Peter Stenvinkel, Paul G Shiels, Peter Kotanko, Pieter Evenepoel, Richard J Johnson","doi":"10.1681/ASN.0000000582","DOIUrl":"10.1681/ASN.0000000582","url":null,"abstract":"<p><p>Planetary health encompasses the understanding that the long-term well-being of humanity is intrinsically linked to the health of global ecological systems. Unfortunately, current practices often overlook this principle, leading to a human-oriented (anthropocentric) worldview that has resulted in heightened greenhouse gas emissions, increased heat stress, lack of access to clean water, and pollution, threatening both the environment and health and survival of Homo sapiens and countless other species. One significant consequence of these environmental changes is the exacerbation of inflammatory and oxidative stressors, which not only contributes to common lifestyle diseases but also accelerates the aging process. We advocate for a shift away from our current anthropocentric frameworks to an approach that focuses on nature's solutions that developed from natural selection over the eons. This approach, which encompasses the field of biomimicry, may provide insights that can help protect against an inflammatory phenotype to mitigate physiological and cellular senescence and provide a buffer against environmental stressors. Gaining insights from how animals have developed ingenious approaches to combat adversity through the evolutionary process of natural selection not only provides solutions for climate change but also confronts the rising burden of lifestyle diseases that accumulate with age.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"311-321"},"PeriodicalIF":10.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739744","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}

{"title":"When a NeF Is Not Enough: Improving Assays in C3 Glomerulopathy.","authors":"Pietro Canetta","doi":"10.1681/ASN.0000000604","DOIUrl":"10.1681/ASN.0000000604","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"174-176"},"PeriodicalIF":10.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950722","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}

{"title":"Targeting Krüppel-Like Factor 2 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":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"193-204"},"PeriodicalIF":10.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801754/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Megalin: A Sidekick or Nemesis of the Kidney?","authors":"Kalyani Kulkarni, Tahir Hussain","doi":"10.1681/ASN.0000000572","DOIUrl":"10.1681/ASN.0000000572","url":null,"abstract":"<p><p>Megalin is an endocytic receptor in the proximal tubules that reabsorbs filtered proteins in the kidneys. Recycling of megalin after endocytosis and its expression on the apical plasma membrane of the proximal tubule are critical for its function. The expression of megalin in the kidney undergoes dynamic changes under physiologic and pathophysiologic conditions. Receptors and various effector signaling components regulate megalin expression and, potentially, function. Genetic manipulation and rare mutations in megalin suggest that a lack of or deficiency in megalin expression/function promotes tubular proteinuria and albuminuria. However, the role of megalin in kidney diseases associated with obesity, diabetes, hypertension, and nephrotoxicity remains unclear. To address these questions, animal and human studies have indicated megalin as a protective, injurious, and potentially urinary marker of nephropathy. This article reviews the literature on the regulation of megalin expression and the role of megalin in the pathophysiology of the kidney under experimental and clinical conditions. Moreover, this review articulates the need for studies that can clarify whether megalin can serve as a therapeutic target, in one way or the other, to treat kidney disease.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"293-300"},"PeriodicalIF":10.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739760","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}

{"title":"Advancing Understanding of Cardiovascular Risk in CKD.","authors":"Vikas S Sridhar, Ayodele Odutayo","doi":"10.1681/ASN.0000000606","DOIUrl":"10.1681/ASN.0000000606","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"36 2","pages":"171-173"},"PeriodicalIF":10.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123090","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}

{"title":"Authors' Reply: Effects of Zibotentan and Dapagliflozin on Fluid Retention in Patients with CKD: Need More Evidence.","authors":"Hiddo J L Heerspink, Johannes David Smeijer","doi":"10.1681/ASN.0000000553","DOIUrl":"10.1681/ASN.0000000553","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"324"},"PeriodicalIF":10.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962301","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}

{"title":"Numerical Flow Simulations of the Shear Stress Forces Arising in Filtration Slits during Glomerular Filtration in Rat Kidney.","authors":"Alexander Fuhrmann, Balazs Pritz, Karlhans Endlich, Wilhelm Kriz","doi":"10.1681/ASN.0000000513","DOIUrl":"10.1681/ASN.0000000513","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"219-230"},"PeriodicalIF":10.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349098","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}