Urate-lowering agents for asymptomatic hyperuricemia in stage 3 - 4 chronic kidney disease: Controversial role of kidney function

Abstract

Because the serum uric acid level increases as the glomerular filtration rate (GFR) decreases, hyperuricemia is associated with chronic kidney disease (CKD). Although hyperuricemia is a risk factor for CKD progression, the causal role of uric acid remains controversial in patients with CKD and asymptomatic hyperuricemia. This study included 588 patients with stage 3-4 CKD and asymptomatic hyperuricemia. Using propensity score matching, 165 pairs treated and untreated with pharmacologic urate-lowering therapy were matched. Kaplan-Meier curves were constructed to determine the effect of urate-lowering agents on kidney survival. The prognostic value for kidney survival was ascertained using Cox regression analysis. The GFR changes over time between the patients treated and untreated with urate-lowering agents were assessed using a linear mixed model analysis. The mean age of the matched patients was 63.2 ± 12.7 years, and 52 (15.8%) patients had diabetic nephropathy. The mean estimated GFR (eGFR) and serum uric acid level were 36.7 mL/min/1.73 m2 and 7.8 mg/dL, respectively. During a mean follow-up period of 41.9 months, 87 developed end-stage kidney disease (ESKD). The incidence rates of ESKD were comparable between the patients treated and untreated with urate-lowering agents. The Kaplan-Meier analysis indicated that kidney survival was also comparable between them. In the multivariate analysis, heart failure and low eGFR were the significant prognostic factors for kidney survival. However, pharmacologic urate-lowering therapy was not predictive of kidney survival. The overall GFR decline rate was also comparable between the groups (P = 0.13). The efficacy of pharmacologic urate-lowering therapy in delaying CKD progression remains controversial. Therefore, further randomized controlled trials are needed to confirm its efficacy in attenuating kidney function deterioration in patients with stage 3-4 CKD.

Fig 1. Patient selection and study flow.

Fig 2. Kaplan-Meier analysis of the cumulative kidney survival of the patients with asymptomatic hyperuricemia.

The dotted line and the solid line depict the patients treated and untreated with pharmacologic urate-lowering therapy, respectively.

Fig 3. Changes in the eGFR over time in the patients with asymptomatic hyperuricemia.

Patients treated with pharmacologic urate-lowering therapy (A) and those untreated with pharmacologic urate-lowering therapy (B). The dark solid lines represent the predicted values. eGFR, estimated glomerular filtration rate.