The Long-Term Effects of the Selective Inhibitor of Urate Transporter 1, Dotinurad, on <span style="mso-fareast-font-family: 'Yu Mincho'; mso-fareast-language: JA;">Metabolic Parameters and Renal Function in Patients<span style="mso-fareast-font-

Background/Objectives: A great number of epidemiological studies have reported that hyperuricemia is associated with the development of hypertension, dyslipidemia, type 2 diabetes, chronic kidney disease (CKD), in addition to metabolic syndrome and insulin resistance. We investigated the effects of long-term treatment with the novel uricosuric drug, a highly selective inhibitor of urate transporter 1 (URAT1), on metabolic parameters and renal function. Methods: We retrospectively picked up patients who had taken dotinurad for the treatment of asymptomatic hyperuricemia, for more than 2 years. We compared metabolic parameters and renal function at baseline with the data at 6, 12, 18, and 24 months after the start of dotinurad. Results: Pharmacologically, dotinurad decreases serum uric acid (UA), by selectively inhibiting URAT1 and decreasing renal reabsorption of UA, which was supported by our result that dotinurad significantly increased urine UA and reduced serum UA. In addition to UA-lowering, dotinurad significantly improved body weight, liver function, serum lipids, and urine albumin. The ATP-binding cassette transporter G2 (ABCG2) regulates renal and intestinal excretion of UA and uremic toxins and strongly affects renal function. Our study also indicates that switching from febuxostat, which inhibits ABCG2, to dotinurad, which does not inhibit ABCG2, was beneficial for maintaining the GFR. Conclusions: Dotinurad may improve obesity, metabolic dysfunction-associated steatotic liver disease (MASLD), and CKD by blocking the entry of UA via URAT1 to adipose tissue, liver, and kidney.