J-shaped association between serum uric acid levels and chronic kidney disease: a cross-sectional study using large health examination data

Abstract

Abstract Introduction Hyperuricemia has been recognized as a risk for cardiovascular disease based on the results of many observational studies. On the other hand, a J-shaped association has been reported in which people with very low serum uric acid levels also have increased cardiovascular risk. Although renal dysfunction is closely associated with cardiovascular disease, there are no reports on whether serum uric acid levels and renal function show a J-shaped association. Hypouricemia, defined as a serum uric acid level of 2.0 mg/dL or less, is relatively common among Japanese, but the absence of symptoms and low prevalence (0.2% in men and 0.4% in women) have made epidemiological studies difficult. Therefore, we used the large-sized data from Japanese population that underwent health examinations and evaluated the association between serum uric acid levels and chronic kidney disease. Methods Data from 227,672 individuals (104,854 men and 122,818 women) who underwent health examinations between 2001 and 2018 were included. All analyses were performed separately for men and women because of sex differences in serum uric acid levels. Participants were classified according to serum uric acid (SUA) quartiles, with hypouricemia SUA below 2.0 mg/dL being classified as a separate category, resulting in five groups (men: ≤2.0, 2.1-5.1, 5.2-5.9, 6.0-6.8, ≥6.9 mg/dL; women: ≤2.0, 2.1-3.7, 3.8-4.4, 4.5-5.1, ≥5.2 mg/dL) to describe the characteristics. We defined chronic kidney disease (CKD) as an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 and examined the association between SUA category and CKD by univariable and multivariable logistic regression analysis, which included age, BMI, alcohol intake, presence of hypertension, dyslipidemia, and diabetes as covariates. Results The characteristics of the population were as follows. Men: age 56 ± 15 years, SUA 5.9 ± 1.3 mg/dL, eGFR 80 ± 17 mL/min/1.73 m2, CKD 9.4%; women: age 57 ± 15 years, SUA 4.5 ± 1.1 mg/dL, eGFR 81 ± 18 mL/min/1.73m2, CKD 9.4%. The results of univariable and multivariable analyses of the association between SUA categories and CKD by gender are shown in Table. Compared to the reference group (men, SUA 2.1-5.1 mg/dL; women, SUA 2.1-3.7 mg/dL), CKD risk was increased not only in the higher uric acid groups but also in the hypouricemia group with SUA 2.0 mg/dL or less. Conclusion For both men and women, serum uric acid levels and CKD prevalence showed a J-shaped association. Uric acid is itself an important antioxidant in vivo, and its absence may have induced a worsening of renal function due to increased oxidative stress.