Uric Acid Level Has a U-Shaped Association with Loss of Kidney Function in Healthy People: A Prospective Cohort Study

BACKGROUND: The relationship between hyperuricemia and chronic kidney disease (CKD) has been found in various observational studies. Although hypouricemia is associated with cardiovascular events, it has not been established as a risk factor for CKD. We investigated the relationship between serum uric acid level and the loss of kidney function and incident CKD in healthy people. MATERIALS AND METHODS: Healthy people were enrolled in this community-based prospective cohort study, the Saitama Cardiometabolic Disease and Organ Impairment Study, Japan. The analysis was conducted on 4188 subjects followed up for at least 3 years, 3102 for 6 years and 1052 for 9 years. Their data including glomerular filtration rate (eGFR) decline were examined every three years. The outcome event was incident CKD or the decrease in eGFR by more than 25% in three years. Multivariate statistical models were adjusted for the baseline characteristics. RESULTS: The following data was obtained: mean±SD age, male, 39.6±10.4 years, female 38.4±10.8 years; eGFR, male, 81.9±16.4 ml/min/1.73m2, female, 82.1±17.5 ml/min/1.73m2; serum uric acid level, male, 5.8±1.2 mg/dl, female, 4.1±0.9 mg/dl. Both low and high serum uric acid levels were associated with the outcome and eGFR decline in males (multivariate logistic additional additive models, linear p = 0.0001, spline p = 0.043; generalized additive models, linear p = 0.0001, spline p = 0.012). In subjects with low serum uric acid levels (male, <5 mg/dl; female, <3.6 mg/dl), multivariate linear mixed models showed that low serum uric acid levels were associated with eGFR decline in a time-dependent manner (male, p = 0.0001; female, p = 0.045). CONCLUSION: This study showed that low as well as high levels of uric acid are associated with the loss of kidney function. Hypouricemia is a candidate predictor of kidney function decline in healthy people.