Dotinurad是一种新型尿酸盐重吸收抑制剂,可延长Alport小鼠的生存期。

IF 3 Q1 UROLOGY & NEPHROLOGY
Kidney360 Pub Date : 2025-08-08 DOI:10.34067/KID.0000000910
Ryosuke Saiki, Kan Katayama, Mutsuki Mori, Lupiya Kimena, Keiko Oda, Yasuo Suzuki, Tomohiro Murata, Ryuji Okamoto, Kaoru Dohi
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引用次数: 0

摘要

背景:高尿酸血症可导致炎性疾病,如痛风,并与肝功能障碍、心血管疾病和免疫细胞激活有关。虽然降尿酸治疗对慢性肾脏疾病(CKD)患者的益处仍不确定,但选择性尿酸转运蛋白1 (URAT1)抑制剂多替努德(dotinurad)可能通过减少过多的尿酸重吸收而对肾脏有益。本研究探讨了多丁尿酸对慢性肾病遗传模型Alport综合征小鼠肾功能的影响。方法:采用小鼠Alport综合征模型,观察多丁纽德对肾脏功能的影响。用多丁尿酸治疗小鼠,评估其寿命、尿白蛋白与肌酐比值、血清肌酐水平、尿尿酸与肌酐比值和血清尿酸水平。组织学分析评估肾小球硬化和小管间质纤维化。此外,进行RNA测序以鉴定基因表达变化,并使用实时逆转录聚合酶链反应(RT-PCR)验证关键发现。结果:dotinurad处理小鼠的寿命明显长于对照组小鼠。他们也表现出较低的尿白蛋白与肌酐比率和血清肌酐水平,而尿尿酸与肌酐比率和血清尿酸水平保持不变。组织学分析显示,多丁努拉德治疗小鼠的肾小球硬化和小管间质纤维化减轻。RNA测序显示炎症细胞因子下调,RT-PCR进一步验证了这一点。结论:这些发现提示多替努拉德可能在CKD中发挥肾脏保护作用。需要进一步的研究来证实这些在临床环境中的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dotinurad, a novel urate reabsorption inhibitor, prolongs survival in Alport mice.

Background: 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-lowering therapy in patients with chronic kidney disease (CKD) remain uncertain, dotinurad, a selective urate transporter 1 (URAT1) inhibitor, may provide renal benefits by reducing excessive uric acid reabsorption. This study investigates the effects of dotinurad on kidney function in a mouse model of Alport syndrome, a genetic model of CKD.

Methods: A mouse model of Alport syndrome was used to evaluate the effects of dotinurad on kidney function. Mice were treated with dotinurad, and their lifespan, urinary albumin-to-creatinine ratios, serum creatinine levels, urinary uric acid-to-creatinine ratios, and serum uric acid levels were assessed. Histological analysis was performed to evaluate glomerulosclerosis and tubulointerstitial fibrosis. Additionally, RNA sequencing was conducted to identify gene expression changes, with real-time reverse transcription polymerase chain reaction (RT-PCR) used to validate key findings.

Results: Dotinurad-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 uric acid levels remained unchanged. Histological analysis demonstrated reduced glomerulosclerosis and tubulointerstitial fibrosis in dotinurad-treated mice. RNA sequencing revealed a downregulation of inflammatory cytokines, which was further validated by RT-PCR.

Conclusions: These findings suggest that dotinurad may exert renoprotective effects in CKD. Further research is needed to confirm these effects in clinical settings.

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来源期刊
Kidney360
Kidney360 UROLOGY & NEPHROLOGY-
CiteScore
3.90
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