Sex-specific Relationship of Serum Uric Acid with All-cause Mortality in Adults with Normal Kidney Function: An Observational Study

Eunjeong Kang, Seung-Sik Hwang, Dong Ki Kim, Kook-Hwan Oh, Kwon Wook Joo, Yon Su Kim, Hajeong Lee

To explain the clinical effect of serum uric acid (SUA) levels as a risk factor for mortality, considering exclusion of kidney function. Participants aged over 40 years who underwent health checkups were recruited. Individuals with estimated glomerular filtrations rates < 60 ml/min/1.73 m(2) and who received laboratory study and colonoscopy on the same day were excluded. SUA levels were higher in men than in women (5.7 ± 1.2 mg/dl for men and 4.2 ± 0.9 mg/dl for women, p < 0.001). During 12.3 ± 3.6 years of followup, 1402 deaths occurred among 27,490 participants. About 6.9% of men and 3.1% of women died. The overall mortality rate had a U-shaped association with SUA levels, a U-shaped association in men, and no association in women. There was a significant interaction of sex for the SUA-mortality association (p for interaction = 0.049); therefore, survival analysis was conducted by sex. In men, the lower SUA group had a higher mortality rate after adjustment (SUA ≤ 4.0 mg/dl, adjusted HR 1.413, 95% CI 1.158-1.724, p = 0.001) compared with the reference group (SUA 4.1-6.0 mg/dl). A higher SUA contributed to an insignificant increased mortality in men (> 8.0 mg/dl, adjusted HR 1.140, 95% CI 0.794-1.636, p = 0.479). Women failed to show any significant association between SUA and mortality. This study provided novel evidence that SUA-mortality association differed by sex. We demonstrated that a lower SUA was an independent risk factor for all-cause mortality in men with normal kidney function.