U-shaped relationship between serum uric acid level and decline in renal function during a 10-year period in female subjects: BOREAS-CKD2

While hyperuricemia is recognized as a risk factor for chronic kidney disease (CKD), the risk of CKD in subjects with a low level of serum uric acid (UA) remains controversial. Here, we examined whether the association of CKD risk with serum UA level differs depending on the sex and age of subjects in a general population. Of subjects who received annual health checkups, we enrolled 6,779 subjects (male/female: 4,454/2,325; age: 45 +/- 9 years) with data from a 10-year follow-up after excluding subjects taking anti-hyperuricemic drugs and those with CKD at baseline. During the follow-up period, 11.4% of the males and 11.7% of the females developed CKD. A significant interaction of sex, but not age, with the effect of baseline UA level on CKD risk was found. A restricted cubic spline analysis showed a U-shaped association of the baseline UA level with the risk of CKD in females. Multivariable Cox proportional hazard analyses for females showed that baseline UA levels in the 5th quintile (Q5, >= 5 mg/dL; HR: 1.68) and the 1st quintile (Q1, <= 3.5 mg/dL; HR: 1.73) were independent risk factors for CKD when compared with UA levels in the 4th quintile (Q4, 4.5-4.9 mg/dL). In males, restricted cubic spline analysis indicated increased CKD risk in subjects with a higher baseline UA level but not in those with a low UA level. In conclusion, a low UA level is a significant risk factor for CKD in females, while an elevated UA level increases the risk of CKD in both sexes.