Kazuko Suzuki

In a non-diabetic Japanese population, the combination of macroalbuminuria and increased urine beta 2-microglobulin predicts a decline of renal function: the Takahata study

BACKGROUND Glomerular and tubular damage are important factors in the development of renal insufficiency. However, the interaction of these factors is largely unknown in the non-diabetic Japanese population. To clarify the relationship between renal insufficiency and both glomerular and tubular damage, we conducted a community-based study using albuminuria and urine beta 2-microglobulin as markers of glomerular and tubular damages, respectively. METHODS Subjects of this study were 2816 non-diabetic individuals >40 years old in Takahata, Japan. The urine albumin-creatinine ratio (UACR) and urine beta 2-microglobulin-creatinine ratio (UBCR) were assessed from single spot urine. The glomerular filtration rate (eGFR) was estimated using the abbreviated MDRD equation with a Japanese coefficient. RESULTS The prevalence of albuminuria (UACR >20 mg/ g in men and >30 mg/g in women), increased UBCR (>300 microg/g) and renal insufficiency (eGFR <60 mL/ min/1.73 m(2)) were 21.0%, 12.5% and 21.7%, respectively, and there was only a small overlap between the three. The mean eGFR was significantly lower in subjects with macroalbuminuria (UACR >200 mg/g in men and >300 mg/g in women) and increased UBCR. No urinary abnormalities were observed in 71.7% of the 611 subjects with renal insufficiency, and were more common in young, women and the non-hypertensive population. The 1-year decline of eGFR was greatest in subjects with an overlap of macroalbuminuria and increased UBCR. CONCLUSIONS This study indicated that only a small part of renal insufficiency accompanied increased urine albumin or beta 2-microglobulin in the non-diabetic Japanese population. The combination of macroalbuminuria and increased urine beta 2-microglobulin might predict faster renal deterioration.

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.

The novel and independent association between single-point SNP of NPHP4 gene and renal function in non-diabetic Japanese population: The Takahata study

Nephronophthisis (NPHP) 4 gene coding nephrocystin-4 is involved in the development of renal tubules and its congenital mutations cause juvenile end-stage renal disease, NPHP. To investigate the association between single-point single-nucleotide polymorphism (SNP) of NPHP4 gene and renal function, we conducted a cross-sectional study in Japanese population. The subjects of this study were non-diabetic general population consisting of 2604 individuals >40 years in Takahata town, Japan. We genotyped 11 SNPs within NPHP4 gene that displayed frequent minor allele frequencies (>0.1) in Japanese general population. Among 11 SNPs in NPHP4 gene, only rs1287637 that induces amino acid substitution (A (Gln)/T (Leu)), located in the acceptor site of exon 21, showed a significant association with estimated glomerular filtration rate (eGFR; T/T: 81.3±15.6 (n=1886), A/T: 82.0±15.5 (n=652) and A/A: 87.4±21.4 ml min−1 per 1.73m2 (n=66); mean±s.d., P=0.006). This SNP was not in linkage disequilibrium with the surrounding SNPs. The multivariate analysis adjusted with possible confounders showed that the A/T+T/T genotype of rs1287637 was independently associated with reduced renal function (eGFR <90 ml min−1 per 1.73m2; odds ratio (OR) 1.75, 95% confidence interval (CI) 1.05–2.94, P=0.033). These results indicate the novel and independent association between single-point SNP rs1287637 in NPHP4 gene and renal function in non-diabetic Japanese population.

Rapid decline in renal function after acute myocardial infarction

AIM To investigate the long term effects of cardiac events on renal function, a prospective study of patients with acute myocardial infarction was conducted. METHODS A total of 137 patients with acute myocardial infarction were followed for 1 year. The change of estimated glomerular filtration rate (eGFR) in cardiac patients was compared with that in background-matched controls, and the factors associated with eGFR changes were analyzed. RESULTS The eGFR decrease was much larger after myocardial infarction, from 73.7 ± 1.9 ml/min/1.73 m2 (mean ± SEM) at baseline to 64.7 ± 1.7 at 1 year, (p < 0.001), compared with that of controls (from 72.8 ± 1.2 to 72.1 ± 1.3, p = 0.305). Multiple regression analysis showed that eGFR change was associated negatively with age, baseline eGFR, proteinuria, and positively with the administration of angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, but not the severity of cardiac damage and comorbidities. Longitudinal analysis 1 year before and 2 years after myocardial infarction showed that eGFR decrease was larger during baseline and 6 months after the event (-7.0 ± 1.0). CONCLUSIONS Renal decline was rapid after myocardial infarction and was affected by clinical characteristics of patients. Careful follow-up of renal function is recommended to prevent the progression of renal and cardiac disease.

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.