The association between genotypes of urate transporter-1, Serum uric acid, and mortality in the community-based population: the Yamagata (Takahata) Study.

BACKGROUND: The urate transporter-1 (URAT1) is crucial in developing hyperuricemia via reabsorption of uric acid in renal tubules, and its function is regulated by several single nucleotide polymorphisms (SNPs) within SLC22A12 gene encoding URAT1. This study investigated whether the genetic predisposition of URAT1 is associated with the mortality in general population. METHODS: This study enrolled 1596 participants (male 45%, mean age 61 years) who registered at local health checkup in Takahata, Japan, and the association between the rs505802 genotypes in SLC22A12 gene and the 7-year mortality, was examined. RESULTS: The serum uric acid levels (mean ± SD) at baseline in the subjects with GG and AG + AA genotypes of rs505802 were 5.1 ± 1.3 mg/dL and 5.0 ± 1.5 mg/dL, respectively. Kaplan-Meier analysis revealed that the mortality was nonsignificantly higher in the subjects with GG genotype than in those with AG + AA genotype (P = 0.09). Cox proportional hazard model adjusted with age, gender, renal function, comorbidities, and other possible confounders, demonstrated that the GG genotype was significantly associated with the mortality [hazard ratio (HR) 2.23, 95% confidence interval (CI) 1.05-4.85, (vs. AG + AA genotype)]. Furthermore, adjustment with serum uric acid levels, along with aforementioned confounders retained the significant association (HR 2.26, 95% CI 1.05-4.85). CONCLUSIONS: This study revealed that the genetic predisposition of URAT1 was independently associated with mortality in the Japanese community-based population. This association might be due to the mechanism independent of serum uric acid levels.

Association between renal function and cardiovascular and all-cause mortality in the community-based elderly population: results from the Specific Health Check and Guidance Program in Japan.

BACKGROUND: Chronic kidney disease is a significant risk factor for end-stage kidney disease, cardiovascular events, and premature death. However, the prognostic value of low estimated glomerular filtration rate (eGFR) in the elderly is debatable. METHODS: We determined eGFR using the Japanese equation in 132,160 elderly subjects (65-75 years) who attended the special health checkup (Tokutei-Kenshin) in 2008 and investigated the association between baseline eGFR and 5-year all-cause and cardiovascular mortality. RESULTS: The median (SD) eGFR was 70.5 ± 15.3 mL/min/1.73 m2. During follow-up, we noted 2045 all-cause deaths including 408 from cardiovascular events. A J-shaped curve was obtained when all-cause and cardiovascular mortality rates were compared with decreases in eGFR, with the highest mortality observed for eGFR <45 mL/min/1.73 m2. These trends were statistically significant in the Kaplan-Meier analysis (P < 0.001). In the Cox proportional hazard analysis, after adjusting for possible confounders, those with eGFR <45 mL/min/1.73 m2, but not eGFR 45-59 mL/min/1.73 m2 showed a higher all-cause and cardiovascular mortality than those with eGFR >90 mL/min/1.73 m2 [hazard ratio (HR) 1.43, 95% confidence interval (CI) 1.06-1.91 for all-cause mortality, HR 2.28, 95% CI 1.28-4.03 for cardiovascular mortality]. Sex-based subgroup analyses showed similar results for both men and women. CONCLUSIONS: We conclude that eGFR <45 mL/min/1.73 m2 is an independent risk factor for all-cause and cardiovascular mortality in the elderly population.

The Association between Glomerular Filtration Rate Estimated Using Different Equations and Mortality in the Japanese Community-Based Population: The Yamagata (Takahata) Study.

BACKGROUND: To evaluate renal function, the indices of estimated glomerular filtration rate (eGFR) obtained using several equations, including the Japanese versions of the serum creatinine-based MDRD equation (eGFRcreat), Chronic Kidney Disease Epidemiology Collaboration equation (eGFR-EPI), and serum cystatin C-based equation (eGFRcys), are utilized. This study prospectively examined the association between these eGFR values and all-cause mortality during a 12-year observational period in a community-based population. METHODS AND RESULTS: The subjects of this study were 1312 participants undergoing a health checkup, aged ≥40 years. In the total population, the mean eGFR values (mL·min-1·1.73 m-2) were 81.5 for eGFRcreat, 78.1 for eGFR-EPI, and 76.6 for eGFRcys. There were 141 deaths during the observation period, and the area under the receiver operating characteristic curve for predicting mortality was 0.59 for eGFRcreat, 0.67 for eGFR-EPI, and 0.70 for eGFRcys (all P < 0.01). In the Cox proportional analysis adjusted for age and sex, eGFRcys, but not eGFRcreat and eGFR-EPI, showed a significant association with all-cause mortality (per 15 mL·min-1·1.73 m-2 decrease: hazard ratio 1.40, 95% confidence interval 1.18-1.67). CONCLUSIONS: This study revealed that eGFRcys showed lower values than eGFRcreat and eGFR-EPI and was significantly associated with all-cause mortality in the Japanese community-based population.