Journal of The American Society of Nephrology最新文献

{"title":"TRPML-1 Dysfunction and Renal Tubulopathy in Mucolipidosis Type IV.","authors":"Giuseppina Grieco, Sandro Montefusco, Edoardo Nusco, Antonella Capuozzo, Francesca Cervellini, Elena Polishchuk, Martha Bishop, Antonio Miele, Luciano D'Apolito, Claudia La Vecchia, Miriam Aurilia, Michela Schiavo, Leopoldo Staiano, Marcella Cesana, Rebecca Oberman, Anna V Lynch, Patricia Musolino, Francesco Trepiccione, Yulia Grishchuk, Diego Luis Medina","doi":"10.1681/ASN.0000000567","DOIUrl":"https://doi.org/10.1681/ASN.0000000567","url":null,"abstract":"<p><strong>Background: </strong>Loss-of-function mutations in the lysosomal channel transient receptor potential cation channel (TRPML-1) cause mucolipidosis type IV (MLIV), a rare lysosomal storage disease characterized by neurological defects, progressive vision loss, and achlorhydria. Recent reports have highlighted kidney disease and kidney failure in patients with MLIV during the second to third decade of life; however, the molecular mechanisms driving kidney dysfunction remain poorly understood.</p><p><strong>Methods: </strong>A cross-sectional review of medical records from 21 patients with MLIV (ages 3–43 years) was conducted to assess kidney function impairment. In addition, we examined the kidney phenotype of MLIV mice at various ages, along with human kidney cells silenced for TRPML-1 and primary tubular cells from wild-type and MLIV mice. Immunohistology and cell biology approaches were used to phenotype nephron structure, the endolysosomal compartment, and inflammation. Kidney function was assessed through proteomic analysis of mouse urine and in vivo kidney filtration measurements.</p><p><strong>Results: </strong>Of the 21 patients with MLIV, only adults were diagnosed with stage 2–3 CKD. Laboratory abnormalities included lower eGFR and higher levels BUN/creatine in blood and proteinuria. In MLIV mice, we observed significant alterations in endolysosomal morphology, function, and impaired autophagy in proximal and distal tubules. This led to the accumulation of megalin (LRP2) in the subapical region of proximal tubular cells, indicating a block in apical receptor–mediated endocytosis. In vivo and in vitro experiments confirmed reduced fluid-phase endocytosis and impaired uptake of ligands, including β-lactoglobulin, transferrin, and albumin in MLIV proximal tubular cells. Urine analysis revealed tubular proteinuria and enzymuria in mice with MLIV. In addition, early-stage disease was marked by increased inflammatory markers, fibrosis, and activation of the proinflammatory transcription factor NF-κB, coinciding with endolysosomal defects. Importantly, adeno-associated viral–mediated TRPML-1 gene delivery reversed key pathological phenotypes in MLIV mice, underscoring TRPML-1's critical role in kidney function.</p><p><strong>Conclusions: </strong>Our findings link TRPML-1 dysfunction to the development of kidney disease in MLIV.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"36 4","pages":"587-601"},"PeriodicalIF":10.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764262","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":"Misprocessing of α -Galactosidase A, Endoplasmic Reticulum Stress, and the Unfolded Protein Response.","authors":"Martina Živná, Gabriela Dostálová, Veronika Barešová, Dita Mušálková, Klára Svojšová, Doria Meiseles, Sara Kinstlinger, Ladislav Kuchař, Befekadu Asfaw, Helena Poupětová, Hana Vlášková, Tereza Kmochová, Petr Vyleťal, Hana Hartmannová, Kateřina Hodaňová, Viktor Stránecký, Lenka Steiner-Mrázová, Aleš Hnízda, Jan Živný, Martin Radina, Miroslav Votruba, Jana Sovová, Helena Trešlová, Larisa Stolnaja, Petra Reková, Lenka Roblová, Eva Honsová, Ivan Rychlík, Moran Dvela-Levitt, Anthony J Bleyer, Aleš Linhart, Jakub Sikora, Stanislav Kmoch","doi":"10.1681/ASN.0000000535","DOIUrl":"10.1681/ASN.0000000535","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"628-644"},"PeriodicalIF":10.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864708","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":"Long-Term Outcomes of Rituximab-Treated Adult Patients with Podocytopathies.","authors":"Philipp Gauckler, Anna Matyjek, Seleni Kapsia, Smaragdi Marinaki, Luis F Quintana, Montserrat M Diaz, Catherine King, Siân Griffin, Raja Ramachandran, Balazs Odler, Kathrin Eller, Ayşe Serra Artan, Safak Mirioglu, Martin Busch, Maxi Schaepe, Kultigin Turkmen, Chee Kay Cheung, Ruth J Pepper, Gema Fernandez Juarez, Julio Pascual, Pilar Auñón, Clara García-Carro, Antolina Rodriguez, Federico Alberici, Leonella Luzardo, Natalia Chebotareva, Ulf Schönermarck, Loreto Fernández, Jai Radhakrishnan, Karina Guaman, Yonatan Peleg, Léa Hoisnard, Vincent Audard, Marios Papasotiriou, Nina Krnanska, Vladimir Tesar, Zdenka Hruskova, Annette Bruchfeld, Maria Stangou, Georgios Lioulios, Stanislas Faguer, David Ribes, Sofiane Salhi, Martin Windpessl, Krešimir Galešić, Matija Crnogorac, Nikola Zagorec, Gert Mayer, Andreas Kronbichler","doi":"10.1681/ASN.0000000520","DOIUrl":"10.1681/ASN.0000000520","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"668-678"},"PeriodicalIF":10.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468646","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":"Combination Therapy with SGLT2 Inhibitors and GLP-1 Receptor Agonists for Diabetic Kidney Disease.","authors":"Mengyao Tang, Mario Luca Morieri, Sahir Kalim, Alessandro Doria","doi":"10.1681/ASN.0000000620","DOIUrl":"10.1681/ASN.0000000620","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"726-729"},"PeriodicalIF":10.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950717","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":"Unlocking the Potential of SC0062: A New Horizon in IgA Nephropathy Treatment?","authors":"Jiachuan Xiong, Jinghong Zhao","doi":"10.1681/ASN.0000000656","DOIUrl":"10.1681/ASN.0000000656","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"744-745"},"PeriodicalIF":10.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515889","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":"Postembryonic Maintenance of Nephron Progenitor Cells with Low Translational Activity in the Chondrichthyan Scyliorhinus canicula.","authors":"Yasmine Lund-Ricard, Julien Calloch, Virginie Glippa, Sam Vandenplas, Ann Huysseune, P Eckhard Witten, Julia Morales, Agnès Boutet","doi":"10.1681/ASN.0000000558","DOIUrl":"10.1681/ASN.0000000558","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"571-586"},"PeriodicalIF":10.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854379","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":"Mechanisms of Cyst Expansion in Polycystic Kidney Disease.","authors":"Kai M Schmidt-Ott","doi":"10.1681/ASN.0000000643","DOIUrl":"10.1681/ASN.0000000643","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"533-535"},"PeriodicalIF":10.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527858","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":"Efficacy and Safety of Ravulizumab in IgA Nephropathy: A Phase 2 Randomized Double-Blind Placebo-Controlled Trial.","authors":"Richard Lafayette, James Tumlin, Roberta Fenoglio, Jessica Kaufeld, Miguel Ángel Pérez Valdivia, Mai-Szu Wu, Shih-Han Susan Huang, Eric Alamartine, Sung Gyun Kim, Min Yee, Andreas Kateifides, Kara Rice, Katherine Garlo, Jonathan Barratt","doi":"10.1681/ASN.0000000534","DOIUrl":"10.1681/ASN.0000000534","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"645-656"},"PeriodicalIF":10.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502829","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":"Adamts1 and Cyst Expansion in Polycystic Kidney Disease.","authors":"Vijayakumar R Kakade, Zafer Akman, Manga Motrapu, Marcelo F Cassini, Leyuan Xu, Gilbert Moeckel, Stefan Somlo, Lloyd G Cantley","doi":"10.1681/ASN.0000000557","DOIUrl":"10.1681/ASN.0000000557","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"559-570"},"PeriodicalIF":10.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605167","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":"ATP-Gated P2X7-Ion Channel on Kidney-Resident Natural Killer T Cells and Memory T Cells in Intrarenal Inflammation.","authors":"Marten Junge, Nastassia Liaukouskaya, Nicole Schwarz, Carolina Pinto-Espinoza, Alessa Z Schaffrath, Björn Rissiek, Christian F Krebs, Guido Rattay, Hans-Willi Mittrücker, Nicola M Tomas, Annette Nicke, Friedrich Haag, Tobias B Huber, Catherine Meyer-Schwesinger, Friedrich Koch-Nolte, Nicola Wanner","doi":"10.1681/ASN.0000000564","DOIUrl":"10.1681/ASN.0000000564","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"602-613"},"PeriodicalIF":10.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829173","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}