Journal of The American Society of Nephrology最新文献

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Characterization of the Cystic Phenotype Associated with Monoallelic ALG8 and ALG9 Pathogenic Variants. 与单等位基因ALG8和ALG9致病变异相关的囊性表型特征
IF 10.3 1区 医学
Journal of The American Society of Nephrology Pub Date : 2025-06-01 Epub Date: 2025-02-03 DOI: 10.1681/ASN.0000000613
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 E 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
{"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 E 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":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1056-1071"},"PeriodicalIF":10.3,"publicationDate":"2025-06-01","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}
引用次数: 0
Genotype-Based Molecular Mechanisms in Alport Syndrome. 基于基因型的Alport综合征分子机制。
IF 10.3 1区 医学
Journal of The American Society of Nephrology Pub Date : 2025-06-01 Epub Date: 2025-02-03 DOI: 10.1681/ASN.0000000647
Emine Bilge Caparali, Vanessa De Gregorio, Moumita Barua
{"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":"1176-1183"},"PeriodicalIF":10.3,"publicationDate":"2025-06-01","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}
引用次数: 0
Implications of Increased Medicare Advantage Enrollment for Access to Kidney Transplant Waitlisting. 增加医疗保险优势登记对获得肾移植等候名单的影响。
IF 10.3 1区 医学
Journal of The American Society of Nephrology Pub Date : 2025-06-01 Epub Date: 2025-02-20 DOI: 10.1681/ASN.0000000667
Joel T Adler, Arnold E Kuk, Kelsey M Drewry, Kevin H Nguyen, Adam S Wilk
{"title":"Implications of Increased Medicare Advantage Enrollment for Access to Kidney Transplant Waitlisting.","authors":"Joel T Adler, Arnold E Kuk, Kelsey M Drewry, Kevin H Nguyen, Adam S Wilk","doi":"10.1681/ASN.0000000667","DOIUrl":"10.1681/ASN.0000000667","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1173-1175"},"PeriodicalIF":10.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468351","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}
引用次数: 0
Clinical Trial End Points for Childhood CKD. 儿童CKD的临床试验终点。
IF 10.3 1区 医学
Journal of The American Society of Nephrology Pub Date : 2025-06-01 Epub Date: 2025-03-14 DOI: 10.1681/ASN.0000000701
Louise Oni, Jennifer McKenzie, Svenja Seide, William E Smoyer, Howard Trachtman
{"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":"10.1681/ASN.0000000701","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1204-1207"},"PeriodicalIF":10.3,"publicationDate":"2025-06-01","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}
引用次数: 0
Authors' Reply: Association between CKD and Kidney Stones: A Reliable Relationship? 作者回复:CKD与肾结石的关联:可靠的关系?
IF 10.3 1区 医学
Journal of The American Society of Nephrology Pub Date : 2025-06-01 Epub Date: 2025-03-26 DOI: 10.1681/ASN.0000000679
Le-Ting Zhou, Muthuvel Jayachandran, Nicholas B Larson, John C Lieske
{"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":"10.1681/ASN.0000000679","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1229"},"PeriodicalIF":10.3,"publicationDate":"2025-06-01","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}
引用次数: 0
Correction: Autoimmune Tubulopathies. 纠正:自身免疫性小管病。
IF 10.3 1区 医学
Journal of The American Society of Nephrology Pub Date : 2025-06-01 Epub Date: 2025-04-07 DOI: 10.1681/ASN.0000000723
Pascal Houillier, Caroline Prot-Bertoye
{"title":"Correction: Autoimmune Tubulopathies.","authors":"Pascal Houillier, Caroline Prot-Bertoye","doi":"10.1681/ASN.0000000723","DOIUrl":"10.1681/ASN.0000000723","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1233"},"PeriodicalIF":10.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795943","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}
引用次数: 0
Questions and Caveats in Antigen-Defined Membranous Nephropathy. 抗原定义膜性肾病的问题和注意事项。
IF 10.3 1区 医学
Journal of The American Society of Nephrology Pub Date : 2025-05-27 DOI: 10.1681/ASN.0000000769
Nicole K Andeen, Vanderlene L Kung, Rupali S Avasare, Sean Barbour, Megan Griffith, Mei Lin Z Bissonnette, Candice Roufosse
{"title":"Questions and Caveats in Antigen-Defined Membranous Nephropathy.","authors":"Nicole K Andeen, Vanderlene L Kung, Rupali S Avasare, Sean Barbour, Megan Griffith, Mei Lin Z Bissonnette, Candice Roufosse","doi":"10.1681/ASN.0000000769","DOIUrl":"https://doi.org/10.1681/ASN.0000000769","url":null,"abstract":"<p><strong>Abstract: </strong>Remarkable progress has been made in the discovery of autoantigens in membranous nephropathy. With increasing testing for membranous antigens in daily practice, it is important to consider the varying strength of association between certain antigens and underlying conditions. This review explores questions and caveats which arise when assessing results of membranous antigen testing. Specifically, we will discuss: 1) discrepancy between tissue antigen and clinical scenario, focusing on PLA2R; 2) one antigen ≠ one clinical condition, i.e., the heterogeneity of membranous antigens seen in one clinical condition (such as in sarcoidosis), and conversely, heterogeneity of conditions associated with one antigen (such as for neural epidermal growth factor-like 1 (NELL1)); 3) rare presence of multiple membranous associated antigens in tissue or blood (such as with anti-protocadherin 7); and 4) lupus membranous nephritis related antigens and their influence on diagnosis or treatment.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159858","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}
引用次数: 0
Alternative Splicing in Mechanically Stretched Podocytes as a Model of Glomerular Hypertension. 机械拉伸足细胞的选择性剪接作为肾小球高血压的模型。
IF 10.3 1区 医学
Journal of The American Society of Nephrology Pub Date : 2025-05-26 DOI: 10.1681/ASN.0000000706
Francescapaola Mattias, Olga Tsoy, Elke Hammer, Alexander Gress, Stefan Simm, Chit Tong Lio, Sabine Ameling, Kerstin Amann, Leonie Dreher, Ulrich Wenzel, Tim Kacprowski, Markus List, Olga Kalinina, Karlhans Endlich, Jan Baumbach, Uwe Völker, Nicole Endlich, Felix Kliewe
{"title":"Alternative Splicing in Mechanically Stretched Podocytes as a Model of Glomerular Hypertension.","authors":"Francescapaola Mattias, Olga Tsoy, Elke Hammer, Alexander Gress, Stefan Simm, Chit Tong Lio, Sabine Ameling, Kerstin Amann, Leonie Dreher, Ulrich Wenzel, Tim Kacprowski, Markus List, Olga Kalinina, Karlhans Endlich, Jan Baumbach, Uwe Völker, Nicole Endlich, Felix Kliewe","doi":"10.1681/ASN.0000000706","DOIUrl":"https://doi.org/10.1681/ASN.0000000706","url":null,"abstract":"<p><strong>Background: </strong>Alterations in pre-mRNA splicing are crucial to the pathophysiology of various diseases. However, the effects of alternative splicing of mRNA on podocytes in hypertensive nephropathy are still unknown. The Sys_CARE project aimed to identify alternative splicing events involved in the development and progression of glomerular hypertension.</p><p><strong>Methods: </strong>Murine podocytes were exposed to mechanical stretch, after which proteins and mRNA were analyzed by proteomics, RNA sequencing and several bioinformatic alternative splicing tools.</p><p><strong>Results: </strong>Using transcriptomic and proteomic analysis, we identified significant changes in gene expression and protein abundance due to mechanical stretch. RNA-Seq identified over 3,000 alternative spliced genes after mechanical stretch, including all types of alternative splicing events. Among these, 17 genes exhibited an alternative splicing event across four different splicing analysis tools. From this group, we focused on Myl6, a component of the myosin protein complex, and Shroom3, an actin-binding protein essential for podocyte function. We identified two Shroom3 isoforms with significant expression changes under mechanical stretch, which was validated by qRT-PCR and in situ hybridization. Additionally, we observed an expression switch of two Myl6 isoforms after mechanical stretch, accompanied by an alteration in the C-terminal amino acid sequence.</p><p><strong>Conclusions: </strong>A comprehensive RNA-Seq analysis of mechanically stretched podocytes identified novel potential podocyte-specific biomarkers and highlighted significant alternative splicing events, notably in the mRNA of Shroom3 and Myl6.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150939","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}
引用次数: 0
mTOR Inhibitors and Vaccine Response in Kidney Transplant Recipients. 肾移植受者mTOR抑制剂和疫苗反应
IF 13.6 1区 医学
Journal of The American Society of Nephrology Pub Date : 2025-05-22 DOI: 10.1681/asn.0000000716
Griffith B Perkins,Matthew J Tunbridge,Cheng Sheng Chai,Christopher M Hope,Arthur Eng Lip Yeow,Tania Salehi,Julian Singer,Bree Shi,Makutiro G Masavuli,Zelalem Addis Mekonnen,Pablo Garcia-Valtanen,Svjetlana Kireta,Julie K Johnston,Christopher J Drogemuller,Beatrice Z Sim,Shane M Spencer,Benedetta C Sallustio,Iain Comerford,George Bouras,Daniela Weiskopf,Alessandro Sette,Anupriya Aggarwal,Vanessa Milogiannakis,Anouschka Akerman,Stuart Turville,Plinio R Hurtado,Tracey Ying,Pravin Hissaria,Simon C Barry,Steven J Chadban,Branka Grubor-Bauk,P Toby Coates
{"title":"mTOR Inhibitors and Vaccine Response in Kidney Transplant Recipients.","authors":"Griffith B Perkins,Matthew J Tunbridge,Cheng Sheng Chai,Christopher M Hope,Arthur Eng Lip Yeow,Tania Salehi,Julian Singer,Bree Shi,Makutiro G Masavuli,Zelalem Addis Mekonnen,Pablo Garcia-Valtanen,Svjetlana Kireta,Julie K Johnston,Christopher J Drogemuller,Beatrice Z Sim,Shane M Spencer,Benedetta C Sallustio,Iain Comerford,George Bouras,Daniela Weiskopf,Alessandro Sette,Anupriya Aggarwal,Vanessa Milogiannakis,Anouschka Akerman,Stuart Turville,Plinio R Hurtado,Tracey Ying,Pravin Hissaria,Simon C Barry,Steven J Chadban,Branka Grubor-Bauk,P Toby Coates","doi":"10.1681/asn.0000000716","DOIUrl":"https://doi.org/10.1681/asn.0000000716","url":null,"abstract":"BACKGROUNDFailure to develop protective immunity in response to vaccination is common among kidney transplant recipients, rendering them susceptible to severe infection. Novel strategies are required. Here, we investigated the potential of mechanistic-target-of-rapamycin (mTOR) inhibitors to improve vaccine responses.METHODSHumoral and cellular responses to primary COVID-19 vaccination (ChAdOx1 or BNT162b2) were assessed for kidney transplant recipients receiving mTOR inhibitor-based (mTOR inhibitor, mycophenolate, prednisolone, N=15) and standard-of-care (tacrolimus, mycophenolate, prednisolone, N=40) immunosuppression, and healthy cohabitants (N=71), in a prospective observational study. Findings were validated and mechanisms explored in mice. Low/non-responding kidney transplant recipients receiving standard-of-care immunosuppression (N=54) were then randomized 1:1 to switch from mycophenolate to sirolimus, or remain on standard-of-care, for 4 weeks prior to receiving COVID-19 booster vaccination. Augmentation of immunity to COVID-19 was assessed as the primary outcome measure.RESULTSA 12-fold greater IFNγ-T cell response to primary vaccination was observed in kidney transplant recipients receiving mTOR inhibitor-based versus standard-of-care immunosuppression (520 vs 43 spot-forming units/106 cells, p < 0.001). A greater frequency of functional memory T cells in the mTOR inhibitor group was observed for both the CD4+ (0.20% vs. 0.05%, p < 0.001) and CD8+ (0.35% vs. 0.07%, p = 0.006) compartments by flow cytometry, and kidney transplant recipients receiving mTOR inhibitor-based immunosuppression produced greater frequencies of SARS-CoV-2-specific CD4+ T cells than healthy cohabitants (1.17% vs 0.48%, p = 0.03). In mice, sirolimus treatment enhanced both recall and de novo T cell responses to homologous and Omicron-specific booster vaccines. Switch from mycophenolate to sirolimus was well tolerated, however no significant difference was observed in the proportion of kidney transplant recipients in the intervention and control arms that achieved protective virus neutralization (10/25 [40%] vs 9/21 [43%] respectively, p = 0.85), nor in T cell response to vaccination (p = 0.89).Conclusions: mTOR inhibition was associated with improved T cell memory formation in kidney transplant recipients, however this effect was not reproduced by a short-term mycophenolate to sirolimus switch strategy.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"33 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122022","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}
引用次数: 0
Expanding the Implications of Proximal Tubular Function Assessment. 扩大近端肾小管功能评估的意义。
IF 13.6 1区 医学
Journal of The American Society of Nephrology Pub Date : 2025-05-21 DOI: 10.1681/asn.0000000743
Chia-Ter Chao
{"title":"Expanding the Implications of Proximal Tubular Function Assessment.","authors":"Chia-Ter Chao","doi":"10.1681/asn.0000000743","DOIUrl":"https://doi.org/10.1681/asn.0000000743","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"18 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144114230","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}
引用次数: 0
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