Uric acid level has a U-shaped association with loss of kidney function in healthy people: a prospective cohort study

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.

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.

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/1.73 m2, female, 82.1 ± 17.5 ml/min/1.73 m2; 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).

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.