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Background: Injury to renal tubules plays an important role in the development of various renal diseases; however, the prevalence and significance of renal tubular damage in the general population are unclear. To clarify this point, we conducted a community-based study, using urinary β(2)-microglobulin as a marker of tubular damage., Methods: The subjects studied were 3,444 Japanese over the age of 40 years. The urinary β(2)-microglobulin-creatinine ratio (UBCR) was assessed in morning spot urine samples., Results: In this population, the distribution of the UBCR among these subjects was skewed towards higher values and a high UBCR (≥300 μg/g) was identified in 438 (12.7%) subjects. However, overlap with macroalbuminuria and renal insufficiency [estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2)] was observed in only 25 (5.7%) and 58 (13.2%) of these subjects, respectively. Multivariate analysis indicated that a high UBCR was positively associated with aging, hypertension, macroalbuminuria and increased urinary sodium excretion. A 5-year longitudinal analysis in 899 subjects indicated a greater decline in eGFR in parallel with the increase in baseline UBCR. After adjustment for possible confounders, a high UBCR was an independent risk factor for rapid decline in eGFR [<-10 mL/min/1.73 m(2); odds ratio 1.79 (95% confidence interval 1.07-2.99), P = 0.026]., Conclusion: This study showed that renal tubular damage was common and was an independent risk factor for renal deterioration in the Japanese population. More attention should be paid to occult renal tubular damage in order to prevent end-stage renal disease.

Paraoxonase-1 (PON1) is an HDL cholesterol-associated antioxidant enzyme, and some of its polymorphisms are linked with systemic oxidative stress and cardiovascular events. In this study, we genotyped seven single nucleotide polymorphisms (SNPs) within the PON1 gene and determined their association with chronic kidney disease in 2,968 individuals from the general Japanese population. We found that a missense SNP (rs662) with a G-to-A substitution leading to an amino acid substitution (G[Arg]/A[Gln]), was significantly associated with albuminuria and estimated glomerular filtration rate (eGFR), especially in women. The A/A genotype in women had the highest prevalence of albuminuria and the lowest values of adjusted eGFR. In contrast, such relationships were not detected in men. Multivariate regression analysis found that the A/A genotype was an independent and significant factor for albuminuria and renal insufficiency (eGFR less than 60 ml/min/1.73 m(2)). The serum PON1 activity was lowest in subjects with the A/A genotype. In biopsy specimens, immunohistochemical analysis found increased PON1 expression on the endothelial surface of sclerotic renal arterioles and glomerular capillaries in patients with hypertension or diabetes. Our study shows that this PON1 G-to-A substitution may be a key player in a common pathway to chronic kidney and cardiovascular diseases in women.

Albuminuria is a risk factor for renal and cardiovascular events and shows a quick change reflecting vascular status. The aim of this study is to examine the frequency and related factors of the short-term change of albuminuria in nondiabetic Japanese population. The study subjects were 1,378 individuals (mean age 63.9 years) who attended community-based health checkup in 2004 and 2005 in Takahata town. Albuminuria was evaluated by urine albumin creatinine ratio in morning urine and was categorized into four stages (low normal, high normal, and micro- and macroalbuminuria). At baseline, the prevalence of subjects with low normal, high normal, and micro- and macroalbuminuria was 62.3, 17.3, 18.7, and 1.7%, respectively. During 1 year, progression and remission of albuminuria stages were observed in 23.1 and 14.5% of total subjects, respectively. Both progression and remission of albuminuria were frequently detected at every stage, especially in high normal albuminuria (29% in progression and 39% in remission, respectively). On multivariate analysis, the changes of albuminuria were associated with older age, blood pressures, total protein, estimated glomerular filtration rate (GFR), and urine sodium excretion at baseline, start of antidiabetic drugs, changes in body weight (±1 kg), hemoglobin (±1 g/dl), and urine sodium excretion (±50 mEq/day). This study revealed that albuminuria showed high variability associated with age and small changes in modifiable risk factors during 1 year. In the treatment and risk analysis of subjects with albuminuria, the effect of these factors should be considered. [ABSTRACT FROM AUTHOR]

The renin-angiotensin-aldosterone system plays a pivotal role in regulation of blood pressure and electrolyte homeostasis and is a target in the treatment of hypertension and renal diseases. However, the factors correlated with plasma renin activity (PRA) are unclarified in general Japanese population. To examine this point, we conducted a community-based cross-sectional study. Subjects of this study were 2,056 individuals (mean age, 61 years; 934 men; 1,122 women) over 40-year-old without antihypertensive medication in Takahata town, Japan. PRA was measured by radioimmunoassay. Estimated 24-h urine sodium (e24hUNa) and potassium excretion were calculated from morning spot urine. The median value of PRA was higher in men compared to women (1.1 ng/ml/h vs. 0.7 ng/ml/h, P < 0.001). The increased PRA (>2.0 ng/ml/h) were detected in 248 men (26.3%) and 142 women (12.7%). One-factor analysis of variance showed that PRA was correlated with blood pressure, uric acid, hemoglobin, total protein, total cholesterol, low-density lipoprotein cholesterol, serum adiponectin and e24hUNa in men. In women, PRA was correlated with age, blood pressure, total protein, high-density lipoprotein cholesterol (HDL-C), serum insulin, e24hUNa and obesity. Multivariate logistic regression analysis showed that high PRA (>2.0 ng/ml/h) was independently associated with low blood pressures, low e24UNa and high serum total protein both in men and women, smoking only in men and high HDL-C only in women, respectively. This study revealed that PRA was higher in men than women and was associated negatively with blood pressures and urine sodium excretion, and positively with total protein, smoking and HDL-C in Japanese population. [ABSTRACT FROM AUTHOR]