Hyperuricemia and deterioration of renal function in autosomal dominant polycystic kidney disease

Abstract

Introduction: The role of hyperuricemia in the renal progression in autosomal dominant polycystic kidney disease (ADPKD) has not been defined well. We investigated the association of serum uric acid (sUA) with renal function, and the effect of hypouricemic treatment on rate of renal progression. Methods: This is a single-center, retrospective, observational cohort study. A total of 365 patients with ADPKD who had estimated glomerular filtration rate (eGFR) ≥ 15 mL/min/1.73 m2 and who were followed up for >1 year were included in our analysis. Hyperuricemia was defined by a sUA level of ≥7.0 mg/dL or when hypouricemic medications were prescribed. Results: Hyperuricemia was associated with reduced initial eGFR, independent of age, sex, hypertension, albuminuria, and total kidney volume. During a median follow-up period of over 6 years, patients with hyperuricemia showed a faster annual decline in eGFR (6.3%/year vs. 0.9%/year, p = 0.008) and higher risk of developing ESRD than the normouricemic patients (34.4% vs. 6.1%, p < 0.001). However, after adjusting for age, sex, hypertension and initial eGFR, sUA was not associated with annual decline in eGFR, nor the development of ESRD. Among 53 patients who received hypouricemic treatment, the annual eGFR decline was significantly improved after hypouricemic treatment (pretreatment vs. posttreatment: −5.35 ± 8.15 vs. 0.21 ± 6.20 mL/min/1.73 m2, p = 0.001 by Wilcoxon signed-rank test). The tissue expression of various urate transporters was increased in proximal tubular epithelial cells of ADPKD. Conclusions: Hyperuricemia may contribute to the decline of renal function in ADPKD. Lowering serum uric acid level may attenuate the rate of disease progression.