Polymorphism of proinflammatory cytokine genes and albuminuria in the Japanese general population: the Takahata study.

BACKGROUND: A cluster of proinflammatory cytokines plays an important role in the development of various renal diseases, and the expression of these cytokines is genetically modified. To examine the association between polymorphisms of proinflammatory cytokine genes and albuminuria, a cross-sectional study was conducted in the general population. METHODS: Single nucleotide polymorphisms (SNPs) in six proinflammatory cytokine genes, including interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor (TNF)-α, CC chemokine ligand 1 (CCL1) and monocyte chemoattractant protein-1 (MCP-1), were genotyped in 2927 Japanese subjects. Urine albumin-creatinine ratio (UACR) was measured in morning spot urine samples. RESULTS: Albuminuria (UACR ≥ 30 mg/g) was significantly associated with the A/A + A/G genotype at rs2069852 in the IL-6 gene (P = 0.01) and the A/A genotype at rs228269 in the CCL1 gene (P = 0.002). Multivariate analysis with adjustment for traditional risk factors showed that these genotypes independently predicted albuminuria [odds ratio (OR) 1.782, 95% confidence interval (CI) 1.171-2.712, P = 0.007 for the A/A + A/G genotype at rs2069852 in IL-6, and OR 1.432, 95% CI 1.128-1.770, P = 0.003 for the A/A genotype at rs228269 in CCL1]. The prevalence of albuminuria and the UACR were increased along with the increase of risk genotypes. CONCLUSIONS: This study revealed that SNPs in the IL-6 and CCL1 genes were associated with albuminuria, and the combination of these genotypes had an additive effect on the prevalence and severity of albuminuria. This indicates that genetic factors influencing inflammatory responses may affect the development of renal injury in the Japanese general population.

The association between renal tubular damage and rapid renal deterioration in the Japanese population: the Takahata study.

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 ß(2)-microglobulin as a marker of tubular damage. METHODS: The subjects studied were 3,444 Japanese over the age of 40 years. The urinary ß(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.