Serum uric acid is associated with incident chronic kidney disease in middle-aged populations: a meta-analysis of 15 cohort studies

Abstract

Background: Mounting evidence indicates that elevated serum uric acid may increase the incidence of chronic kidney disease (CKD). Our goal was to systematically evaluate longitudinal cohort studies for the association of serum uric acid levels and incident CKD.

Methods: We searched electronic databases and the reference lists of relevant articles. The primary outcome was incident CKD, which was defined as an eGFR less than 60 mL/min/1.73 m2 at the follow-up examination. Study-specific risk estimates were combined using random-effects models. The included studies were stratified into subgroups, and meta-regression analyses were performed.

Results: Fifteen unique cohorts with a total of 99,205 individuals and 3,492 incident CKD cases were included. The relative risk of CKD was 1.22 (95% CI 1.16-1.28, I2 = 65.9%) per 1 mg/dL serum uric level increment. This positive association was consistently observed in subgroups stratified according to most of the study-level characteristics. The observed positive association was more pronounced among group with a mean age <60 years (RR 1.26, 95% CI 1.21-1.31), and low-level heterogeneity was observed in the findings for this age group (I2 = 46.4%, P = 0.022). However, no association was observed among studies with a mean age≥60 years (RR 1.04, 95% CI 0.96-1.13), and no evidence of heterogeneity was evident among the studies (I2 = 0%, P = 0.409). This mean age-related difference in the association between serum uric acid levels and CKD was significant (P = 0.004). The sensitivity analysis results were consistent when the analyses were restricted to studies that controlled for proteinuria and metabolic syndrome.

Conclusions: Our meta-analysis demonstrated a positive association between serum uric acid levels and risk of CKD in middle-aged patients independent of established metabolic risk factors. Future randomized, high-quality clinical trials are warranted to determine whether lowering uric acid levels is beneficial in CKD.

Figure 1. Flow chart of study selection.

This flow chart depicts the literature search for longitudinal cohort studies reporting the relationship between the serum uric acid (SUA) level and chronic kidney disease (CKD).

Figure 2. Relative risks for the association between serum uric acid (for a 1 mg/dL increase) and the incidence of CKD.

Squares represent study-specific relative risks (the square sizes are proportional to the weight of each study in the overall estimate), horizontal lines represent 95% confidence intervals, and diamonds represent the overall relative risk estimate with its 95% CI.

Figure 3. Plot of the RR of CKD associated with a 1 mg/dL increase in the serum uric acid level among individuals according to mean age.

The RR was pooled within subgroups with similar mean ages using random-effects model meta-analysis.