Serum Urate and Risk of Chronic Kidney Disease: A Mendelian Randomization Study Using Taiwan Biobank

Abstract

ObjectiveTo evaluate the association between serum urate and risk of incident chronic kidney disease (CKD) and to assess whether serum urate plays a causal role in CKD. Patients and MethodsWe conducted a prospective cohort study and Mendelian randomization analysis that analyzed longitudinal data from the Taiwan Biobank between January 1, 2012, and December 31, 2021. ResultsA total of 34,831 individuals met the inclusion criteria, of which 4697 (13.5%) had hyperuricemia. After a median (interquartile range) follow-up of 4.1 (3.1-4.9) years, 429 participants developed CKD. After adjustment for age, sex, and comorbid conditions, each mg/dL increase in serum urate was associated with a 15% higher risk of incident CKD (HR, 1.15; 95% CI, 1.08 to 1.24; P<.001). The genetic risk score and seven Mendelian randomization methods revealed no significant association between serum urate levels and the risk of incident CKD (HR, 1.03; 95% CI, 0.72 to 1.46; P=0.89; all P>.05 for 7 Mendelian randomization methods). ConclusionThis prospective, population-based cohort study showed that elevated serum urate is a significant risk factor for incident CKD; however, Mendelian randomization analyses failed to provide evidence that serum urate had a causal effect on CKD in the East Asian population.