A formula predicting the effective dose of febuxostat in chronic kidney disease patients with asymptomatic hyperuricemia based on a retrospective study and a validation cohort .

Abstract

Febuxostat is initiated in chronic kidney disease (CKD) patients to lower uric acid but without any renal dosing scheme. This study aimed to determine a formula that predicts the effective dose of febuxostat in patients with an estimated glomerular filtration rate (eGFR) < 60mL/min and asymptomatic hyperuricemia. This is a retrospective analysis of 100 CKD patients treated with febuxostat for asymptomatic hyperuricemia in two private Lebanese clinics. Patients with gout were excluded. Collected variables were age, sex, weight, serum creatinine, serum uric acid (sUA) before and after febuxostat, dose of febuxostat used, and diuretic use. Multiple regression analysis was used to derive a formula predicting the dose of febuxostat based on eGFR (2009 Chronic Kidney Disease Epidemiology Collaboration equation), baseline sUA, and sUA reduction ratio. A prospective cohort of 24 patients was then used to validate the derived model. 100 patients were included with a median age of 71.5 years (interquartile range (IQR), 64.2-79.0); 69% were men. Median baseline sUA was 9.1mg/dL (IQR, 8.4-10.1). Mean eGFR was 31.80±12.96 mL/min/1.73m2. Of the included patients, 18% had CKD stage 3a, 36% had CKD stage 3b, 38% had CKD stage 4, and 8% had non-dialysis CKD stage 5. A formula was computed to predict febuxostat dosing. Variables that were predictive of febuxostat dose and used in the final equation were eGFR, diuretic use, baseline sUA, and sUA reduction ratio. The validation cohort showed no significant difference between the expected sUA and the measured one (p = 0.16). With this new formula, physicians can initiate febuxostat in CKD patients at an effective dose for any desired sUA reduction ratio.