Association of Uric Acid With Change in Kidney Function in Healthy Normotensive Individuals

Background

Despite recent evidence, the role of uric acid as a causal factor in the pathogenesis and progression of kidney disease remains controversial, partly because of the inclusion in epidemiologic studies of patients with hypertension, diabetes, and/or proteinuria.

Study Design

Prospective observational cohort.

Setting & Participants

900 healthy normotensive adult blood donors (153 women, 747 men) evaluated at baseline and after 5 years.

Predictor

Serum uric acid level.

Outcomes

Decrease in estimated glomerular filtration rate (eGFR) >10 mL/min/1.73 m², computed using the Modification of Diet in Renal Disease (MDRD) Study equation, with secondary analyses examining similar decreases using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Cockcroft-Gault equations.

Results

During a median follow-up of 59 months, eGFR decreased from 97 ± 16 to 88 ± 14 mL/min/1.73 m². Higher serum uric acid levels were associated with a greater likelihood of eGFR decrease in both women and men (HR, 1.13 [95% CI, 1.04-1.39] per each 1-mg/dL increase in uric acid level); in multivariable analyses adjusting for age, sex, body mass index, blood glucose level, total cholesterol level, mean blood pressure, urine albumin-creatinine ratio, and serum triglyceride level, the association remained highly significant (HR, 1.28 [95% CI, 1.12-1.48]). Results were similar using different estimating equations and when the association was examined in sex-specific subgroups.

Limitations

Analyses were based on a single baseline uric acid measurement. Women are underrepresented.

Conclusions

In healthy normotensive individuals, serum uric acid level is an independent risk factor for decreased kidney function.

Index Words: Uric acid, glomerular filtration rate, risk factor decline