Kazunobu Ichikawa

Hyperuricemia is associated with all-cause and cardiovascular mortality. However, the threshold value of serum uric acid levels for increased risk of mortality has not been determined. This large-scale cohort study used a nationwide database of 500,511 Japanese subjects (40-74 years) who participated in the annual health checkup and were followed up for 7 years. The association of serum uric acid levels at baseline with cardiovascular and all-cause mortality was examined. The Cox proportional hazard model analysis with adjustment for possible confounders revealed that the all-cause and cardiovascular mortality showed a J-shaped association with serum uric acid levels at baseline in both men and women. A significant increase in the hazard ratio for all-cause mortality was noted with serum uric acid levels ≥ 7 mg/dL in men and ≥ 5 mg/dL in women. A similar trend was observed for cardiovascular mortality. This study disclosed that even a slight increase in serum uric acid levels was an independent risk factor for all-cause and cardiovascular mortality in both men and women in a community-based population. Moreover, the threshold values of uric acid for mortality might be different for men and women.

OBJECTIVE: The metabolic syndrome is associated with an increased risk of chronic kidney disease, cardiovascular disease and mortality. However, the association between microalbuminuria and the metabolic syndrome has not yet been reported in the general population in Japan. Therefore, we undertook a population-based study to examine the association between microalbuminuria and the metabolic syndrome in Takahata, Japan. METHODS: Subjects of this cross-sectional study were individuals aged from 40 to 87 years old. The metabolic syndrome was defined according to the criteria of the Adult Treatment Panel III. Microalbuminuria was defined as a urine albumin-creatinine ratio of 30 to 300 mg/g. RESULTS: A total of 2,321 subjects (mean age 64 years old) were entered into the final analysis. Among them, the prevalence of the metabolic syndrome and microalbuminuria was 16.5% and 13.7%, respectively. There was a significantly positive correlation between the number of components of the metabolic syndrome and the corresponding prevalence of microalbuminuria (p<0.001). In the subjects with metabolic syndrome compared with those without metabolic syndrome, the age- and gender-adjusted odds ratio of microalbuminuria was 1.99 (95% CI, 1.49-2.66). Multiple logistic regression analysis revealed that high glucose, high blood pressure and obesity were independently associated with microalbuminuria. CONCLUSIONS: Our study revealed a strong relationship between microalbuminuria and the metabolic syndrome in the general population in Japan. More comprehensive and intensive management of the metabolic syndrome at its early stage is important to prevent the progression of renal injury and cardiovascular complications.

BACKGROUND: Hypertension and proteinuria are risk factors for adverse renal outcomes in patients with chronic kidney disease. This study investigated the associations of blood pressure and proteinuria on renal function in a community-based population. METHODS: We analyzed data from a nationwide database of 141,514 subjects who participated in the annual "Specific Health Check and Guidance in Japan" checkup in 2008 and 2010. The study subjects were aged between 29 and 74 years, and the cohort comprised 40% men. We examined relationships between blood pressure levels, proteinuria at baseline, and the 2-year change in the estimated glomerular filtration rate (eGFR), which was determined using the Japanese equation. RESULTS: After adjusting for possible confounders, the change in the eGFR was inversely correlated with systolic blood pressure (SBP), but not diastolic blood pressure (DBP), at baseline, irrespective of the presence of proteinuria. Compared with the lowest SBP sixtile (≤118mm Hg), eGFRs declined significantly at SBPs ≥ 134mm Hg in subjects with proteinuria, while eGFRs declined significantly at SBPs ≥ 141mm Hg in those without proteinuria. At the same SBPs, renal function decline was faster and the risk for incident renal insufficiency was higher in subjects with proteinuria compared with those without proteinuria. CONCLUSIONS: This study showed that a difference in SBP, but not DBP, is independently associated with a rapid eGFR decline in the general Japanese population, and that the association of SBP on the decline of renal function was greater in subjects with proteinuria compared with those without proteinuria.

BACKGROUND: Hyperuricemia is a risk factor for adverse renal outcomes in patients with chronic kidney disease. This study investigated the effect of uric acid on renal function in a community-based population. METHODS: We used a nationwide database of 165 847 subjects (aged 29-74, male 40%) who participated in the annual 'Specific Health Check and Guidance in Japan' checkup between 2008 and 2010; we examined the relationship between serum uric acid levels at baseline and 2-year change in the estimated glomerular filtration rate (eGFR) obtained by using the Japanese equation. RESULTS: After adjusting for possible confounders, the eGFR change was inversely correlated with uric acid at baseline. In the multivariable analysis, the decline in eGFR was significantly more rapid in subjects with the slight increase in uric acid (males ≥5.7 mg/dL, females ≥4.4 mg/dL), and the risk for incidental renal insufficiency (eGFR <60 mL/min/1.73 m(2)) was increased at uric acid of ≥6.3 mg/dL in males and ≥5.5 mg/dL in females, compared with the lowest quintile. The multiple linear regression analysis revealed that the effect of uric acid on eGFR changes was significant, especially in females, those with proteinuria and diabetes and those without alcohol consumption. CONCLUSION: This study showed that serum uric acid is independently associated with a more rapid decline of eGFR and incident renal insufficiency, and that a slight increase within the normal range of serum uric acid might be a risk for renal damage in the general population.