P0180U-SHAPED RELATIONSHIP BETWEEN SERUM URIC ACID LEVEL AND THE RISK OF END STAGE RENAL DISEASE AND ALL-CAUSE MORTALITY IN MEN

Abstract

Abstract Background and Aims High uric acid level was known as a risk factor to incident chronic kidney disease, mortality, or cardiovascular mortality. However, it is obscure which level of uric acid (UA) is safe to prevent end stage renal disease (ESRD) and mortality. We searched the optimal range of UA level to escape the incident ESRD and death in a large cohort of general population. Method We enrolled 143,762 adult subjects participated in voluntary health check-up program from three referral hospitals in Korea between 1995 and 2009. We defined 48,147 control subjects (CONTROL) without risk factors of high UA level, to calculate 5, 20, 80, and 95 percentiles of UA level and allocated whole participants into five groups (G1, G2, G3, G4, G5) according to the criteria in each gender. We merged the incident data of ESRD from the Korean ESRD registry by December 2017 and the mortality data from the Ministry of the Interior and Safety by May 2018 based on the identifier of Koreans. This project was approved by institutional review boards of the three hospitals. Results The UA levels of 5, 20, 80, 95 percentiles in CONTROL were 2.9 mg/dL, 3.5 mg/dL, 4.9 mg/dL, and 5.7 mg/dL in females, and 4.1 mg/dL, 5.0 mg/dL, 6.8 mg/dL, and 7.8 mg/dL in males. There were 76,784 (53.4%) males and 66,978 (46.6%) females. The age was 50.5 ± 12.2 years and the level of GFR by CKD-EPI equation was 94.3 ± 15.2 ml/min/1.73 m2 at enrollment. Among females, ESRD was developed in 110 subjects (0.2%) and 1,922 subjects (2.9%) were dead during more than 12 years. The level of UA and groups of UA were not independent risk factors to mortality or incident ESRD in females. Among males, there were 162 subjects with ESRD (0.2%) and 4293 subjects (5.6%) were dead. Compared to G3 group (5.0 mg/dL ≤ UA<6.8 mg/dL), other groups showed higher risk of incident ESRD adjusted with related factors by Cox’s hazard proportional model in males (p=0.016). The Hazard ratios (HRs) for incident ESRD in G1 group (<4.1 mg/dL), G4 group (6.8 mg/dL ≤ UA< 7.8 mg/dL), and G5 group (7.8 mg/dL ≤ UA) were 2.409 (95% CI, 1.312-4.423, P=0.005), 1.710 (95% CI, 1.080-2.707, P=0.022), and 1.742 (95% CI, 1.098-2.762, P=0.018), respectively. The HRs for all-cause mortality in G1, G4, and G5 group were 1.203 (95% CI, 1.017-1.346, P=0.001), 1.099 (95% CI, 1.006-1.201, P=0.037), and 1.137 (95% CI, 1.015-1.272, P=0.026), respectively. We found there were 591 subjects died from cardiovascular disease (CVD) among 3,352 deaths with valid cause of death. G1 and G5 group showed higher risk for CVD-mortality compared to G3 group in men (p<0.001). Conclusion Serum uric acid level showed U-shaped pattern of HRs for incident ESRD and all-cause mortality in men, only. The appropriate uric acid level might be 4.1-6.7 mg/dL in men.