Kosuke Kudo

Increases in urinary albumin and beta2-microglobulin are independently associated with blood pressure in the Japanese general population: the Takahata Study

Essential hypertension is a multifactorial disorder and a risk factor for renal failure and cardiovascular disease. Recently it was hypothesized that subtle acquired renal injury such as renal microvascular and tubulointerstitial damage induces salt-sensitive hypertension. The objective of this study was to examine the relationship between blood pressure and renal abnormalities in the Japanese general population. The participants in this community-based, cross-sectional study were 1,965 subjects over 40 years old, without renal insufficiency and antihypertensive medication. Urine albumin–creatinine ratio (UACR) and beta2-microglobulin–creatinine ratio (UBCR) were measured in single spot urine samples, as markers of renal microvascular and tubulointerstitial damage, respectively. Multiple linear regression analysis showed a significant positive correlation of blood pressure with UACR and UBCR, but not with estimated glomerular filtration rate. In multiple logistic regression analysis, the increases in UACR and UBCR were independently associated with hypertension, after adjustment for possible confounders. Higher levels of UACR (⩾5.9 mg g−1) and UBCR (⩾145 μg g−1) were associated with a significantly higher risk of hypertension, compared with UACR ⩽5.8 mg g−1 and UBCR ⩽84.5 μg g−1, respectively. Furthermore, there was a positive relationship between urinary sodium excretion and blood pressure in subjects with high UBCR tertile. This study showed that the increases in urinary albumin and beta2-microglobulin were independently associated with blood pressure in a general population. These renal abnormalities may be differentially related to the development of hypertension.

Comparison of Mortality between Japanese Peritoneal Dialysis and Hemodialysis Patients: A 5-Year Multicenter Follow-Up Study

To examine the relationship between dialysis modality and prognosis in Japanese patients, we conducted a prospective multicenter observational study. We recruited 83 background-matched peritoneal dialysis (PD) and 83 hemodialysis (HD) patients (average age, 64.9 years; men, 53.6%; diabetic patients, 22.9%; median duration of dialysis, 48 months in all patients) and followed them for 5 years. During the follow-up period, 27 PD patients (16 cardiovascular and 11 non-cardiovascular deaths) and 27 HD patients died (14 cardiovascular and 13 non-cardiovascular deaths). There were 8 PD patients switched to HD, and 6 PD patients received renal transplantation. Kaplan-Meier analysis revealed that the crude survival rate was not significantly different at the end of 5 years (PD 67.5% versus 67.5%, log-rank P = 0.719). The difference in cardiovascular and non-cardiovascular mortalities between PD and HD was not statistically significant. Multivariate Cox analysis showed that the independent predictors for death were age and serum albumin levels, but not the dialysis modality. This study showed that the overall mortality was not significantly different between PD and HD patients, which suggests that dialysis modality might not be an independent factor for survival in Japanese patients.

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)-1β, 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.