Original Investigation
Pathogenesis and Treatment of Kidney Disease
Association of Uric Acid With Change in Kidney Function in Healthy Normotensive Individuals

https://doi.org/10.1053/j.ajkd.2010.01.019Get rights and content

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.

Section snippets

Methods

Between May and October 2003, a total of 900 apparently healthy persons (153 women, 747 men) with an age range of 20-65 years were recruited from blood donors at our hospital transfusion center after excluding those with known diabetes and/or hypertension, nephropathies (such as glomerulonephritis, pyelonephritis, hereditary kidney disease, and kidney stones), gout, or positive history of cardiovascular disease (stroke, transitory ischemic attacks, coronary heart disease, and peripheral

Results

Uric acid quartile-specific demographic, clinical, and biochemical parameters of participants studied at baseline and completion of the study are listed in Table 1 for women and Table 2 for men. eGFR decreased to <60 mL/min/1.73 m2 in 12 participants (11 men, 1 woman) according to the MDRD Study equation and in 11 (10 men, 1 woman) according to the CKD-EPI equation. No study participant developed gout and/or diabetes during follow-up, 4 developed impaired fasting glucose levels, and 17 (13 men,

Discussion

Results of our study show that even in a sample of healthy persons, GFR decreases over time, and uric acid level is an independent risk factor for such a decrease. The eGFR decrease observed in our study was larger than expected compared with previous population studies from Asia, Europe, and the United States30, 31, 32; such a finding may be explained in part by a regression to the mean phenomenon after exclusion from the study of persons with increased serum creatinine levels and in part by

Acknowledgements

Support: None.

Financial Disclosure: The authors declare that they have no relevant financial interests.

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    Originally published online as doi:10.1053/j.ajkd.2010.01.019 on April 12, 2010.

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