[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-452662-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-452662-en":131},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","dotinurad-a-novel-urate-reabsorption-inhibitor-prolongs-survival-in-alport-mice","Dotinurad, a Novel Urate Reabsorption Inhibitor, Prolongs Survival in Alport Mice","","Hyperuricemia drives inflammatory disorders such as gout and is linked to liver dysfunction, cardiovascular disease, and immune cell activation. Benefits of urate-lowering therapy in chronic kidney disease (CKD) remain uncertain. This study evaluates dotinurad, a selective URAT1 inhibitor, for renal effects in Alport syndrome mice. Treated animals were assessed for kidney function, urinary albumin and uric acid handling, histology, and inflammatory gene expression.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/dotinurad-a-novel-urate-reabsorption-inhibitor-prolongs-survival-in-alport-mice/452662/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/dotinurad-a-novel-urate-reabsorption-inhibitor-prolongs-survival-in-alport-mice/452662.png","ImageObject",300,407,{"name":42,"@type":43},"LangkahRina","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-09","2026-09-30",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",13,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is dotinurad and what role does URAT1 play in this study?","Question",{"text":63,"@type":64},"Dotinurad is a selective URAT1 inhibitor. URAT1 in kidney proximal tubules mediates urate reabsorption, so inhibiting URAT1 targets excessive uric acid reabsorption.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Which outcomes were used to evaluate kidney effects in the Alport mouse model?",{"text":68,"@type":64},"The study measured lifespan, urinary albumin-to-creatinine ratios, serum creatinine, urinary uric acid-to-creatinine ratios, serum uric acid levels, and performed histologic assessment of glomerulosclerosis and tubulointerstitial fibrosis.",{"name":70,"@type":61,"acceptedAnswer":71},"What did the study find about survival and kidney pathology after dotinurad treatment?",{"text":72,"@type":64},"Dotinurad-treated mice had a significantly longer lifespan and showed lower urinary albumin-to-creatinine ratios and serum creatinine. Histology demonstrated reduced glomerulosclerosis and tubulointerstitial fibrosis.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},452662,1790810716,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146,"preview_page_count":4},962090893776,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Basic Research  \nDotinurad, a Novel Urate Reabsorption Inhibitor, Prolongs Survival in Alport Mice  \nRyosuke Saiki  , Kan Katayama  , Mutsuki Mori, Lupiya Kimena  , Keiko Oda, Yasuo Suzuki  , Tomohiro Murata, Ryuji Okamoto  , and Kaoru Dohi   \nKey Points  \nc Dotinurad treatment slows the progression of kidney disease in a mouse model of Alport syndrome, a genetic model of CKD.  \nc Dotinurad may represent a potential therapeutic strategy for CKD management.  \nAbstract  \nBackground Hyperuricemia contributes to inflammatory conditions such as gout and is associated with liver dysfunction, cardiovascular disease, and immune cell activation. While the benefits of uric acid (UA)–lowering therapy in patients with CKD remain uncertain, dotinurad (DD), a selective urate transporter 1 (URAT1) inhibitor, may provide renal benefits by reducing excessive UA reabsorption. This study investigates the effects of DD on kidney function in a mouse model of Alport syndrome, a genetic model of CKD.  \nMethods A mouse model of Alport syndrome was used to evaluate the effects of DD on kidney function. Mice were treated with DD, and their lifespan, urinary albumin-to-creatinine ratios, serum creatinine levels, urinary uric acid-tocreatinine ratios, and serum UA levels were assessed. Histologic analysis was performed to evaluate glomerulosclerosis and tubulointerstitial fibrosis. In addition, RNA sequencing was conducted to identify gene expression changes, with realtime RT-PCR used to validate key findings.  \nResults DD-treated mice exhibited a significantly longer lifespan than control mice. They also showed lower urinary albumin-to-creatinine ratios and serum creatinine levels, while urinary uric acid-to-creatinine ratios and serum UA levels remained unchanged. Histologic analysis demonstrated reduced glomerulosclerosis and tubulointerstitial fibrosis in DD-treated mice. RNA sequencing revealed a downregulation of inflammatory cytokines, which was further validated by RT-PCR.  \nConclusions These findings suggest that DD may exert renoprotective effects in CKD. Further research is needed to confirm these effects in clinical settings.  \nKidney360 6: 1671–1681, 2025. doi: [https://doi.org/10.34067/KID.0000000910](https://doi.org/10.34067/KID.0000000910)  \nIntroduction  \nIndividuals with hyperuricemia may develop gout, a painful inflammatory arthritis characterized by monosodium urate crystal formation in joint tissues.1 Hyperuricemia leads to the infiltration of immune cells and an escalated overexpression of inflammatory cytokines by these immune cells.2 Possible mechanisms include regulation of uric acid (UA) in monocytes, inducing macrophages to create inflammatory cytokines, and activating macrophage phagocytosis.2  \nRegarding specific effects on organs, high serum UA level is related to liver enzymes activity and nonalcoholic fatty liver disease.3,4 There are also reports on the relationship between cardiovascular and serum UA levels.5,6 A systematic review of the association between UA levels and cardiovascular death has shown a positive correlation between elevated serum UA levels and increased risk of cardiovascular death.7  \nBy contrast, there is a paucity of conclusive evidence supporting the efficacy of UA-lowering therapy in the  \nDepartment of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan Correspondence: Dr. Kan Katayama, email: [katayamk@med.mie-u.ac.jp](katayamk@med.mie-u.ac.jp)  \n[Received:](Received: March 6)[ March 6](Received: March 6), 2025 Accepted: July 25, 2025  \nPublished Online Ahead of Print: August 8, 2025  \nCopyright © 2025 The Author(s) . Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used","cbCaiuY3d8CVH2JE","https://ap.wps.com/l/cbCaiuY3d8CVH2JE","pdf",1106961,11,"English","# Background\n# Methods\n## Animal experiments\n## RNA sequencing and validation\n# Results\n# Conclusions\n# Introduction","[{\"question\":\"What is dotinurad and what role does URAT1 play in this study?\",\"answer\":\"Dotinurad is a selective URAT1 inhibitor. URAT1 in kidney proximal tubules mediates urate reabsorption, so inhibiting URAT1 targets excessive uric acid reabsorption.\"},{\"question\":\"Which outcomes were used to evaluate kidney effects in the Alport mouse model?\",\"answer\":\"The study measured lifespan, urinary albumin-to-creatinine ratios, serum creatinine, urinary uric acid-to-creatinine ratios, serum uric acid levels, and performed histologic assessment of glomerulosclerosis and tubulointerstitial fibrosis.\"},{\"question\":\"What did the study find about survival and kidney pathology after dotinurad treatment?\",\"answer\":\"Dotinurad-treated mice had a significantly longer lifespan and showed lower urinary albumin-to-creatinine ratios and serum creatinine. Histology demonstrated reduced glomerulosclerosis and tubulointerstitial fibrosis.\"}]","Dotinurad, a Novel Urate Reabsorption Inhibitor, Prolongs Survival in Alport Mice | PDF",1790737543,28]