Abstract
<jats:p>Recently, an observational study demonstrated that a lower fractional excretion of uric acid (FEUA) is significantly associated with a higher risk of kidney failure. This study aimed to assess the efficacy of switching from febuxostat to dotinurad, which increases FEUA, in patients with chronic kidney disease (CKD) and hyperuricemia (HUA).This was a non-randomized, open-label, single-center, prospective, single-arm study involving 60 patients with CKD and HUA who received febuxostat. Participants first underwent a 3-month observation period, followed by a 3-month intervention period, during which treatment was switched from febuxostat to dotinurad. The primary outcomes were changes from baseline to 3-months after switching in the estimated glomerular filtration rate (eGFR) calculated from serum creatinine (eGFRcreat) and serum cystatin C (eGFRcys), as well as the serum uric acid levels. The secondary outcome was defined as the correlation betweenΔFEUA and the changes in both eGFRcreat(ΔeGFRcreat) and eGFRcys(ΔeGFRcys), respectively. During the observation period, mean eGFRcreat decreased significantly. The baseline eGFRcreat (mL/min/1.73 m²) was 36.0 ± 15.2, and the serum urate level (mg/dL) was 5.5 ± 1.2. During the intervention period, eGFRcreat increased in contrast to the significant decline observed in eGFRcys. After 3 months of switching to dotinurad, the mean serum UA levels increased significantly from 5.5 ± 1.2 to 6.1 ± 1.4 mg/dL, despite a significant elevation in FEUA. Both ΔeGFRcreat and ΔeGFRcys after switching to dotinurad were positively correlated with ΔFEUA. Switching from febuxostat to dotinurad resulted in discrepant changes in eGFRcreat and eGFRcys, suggesting that renal function should be assessed carefully after switch. Additionally, the risk of elevated serum UA levels should be considered when switching from febuxostat to dotinurad in patients with CKD.</jats:p>