Key Points:
Dotinurad treatment slows the progression of kidney disease in a mouse model of Alport syndrome, a genetic model of CKD.
Dotinurad may represent a potential therapeutic strategy for CKD management.
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 (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.
Methods: 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-to-creatinine 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 real-time RT-PCR used to validate key findings.
Results: 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.
Conclusions: These findings suggest that DD may exert renoprotective effects in CKD. Further research is needed to confirm these effects in clinical settings.
Keywords: CKD; alport syndrome.