Baseline characteristics and prevalence of cardiovascular disease in newly visiting or referred chronic kidney disease patients to nephrology centers in Japan: a prospective cohort study.

BACKGROUND: About 39,000 patients were newly prescribed renal replacement therapy in Japan in 2011, resulting in a total of more than 300,000 patients being treated with dialysis. This high prevalence of treated end stage kidney disease (ESKD) patients is an emergent problem that requires immediate attention. We launched a prospective cohort study to evaluate population specific characteristics of the progression of chronic kidney disease (CKD). In this report, we describe the baseline characteristics and risk factors for cardiovascular disease (CVD) prevalence among this cohort. METHODS: New patients from 16 nephrology centers who were older than 20 years of age and who visited or were referred for the treatment of CKD stage 2-5, but were not on dialysis therapy, were recruited in this study. At enrollment, medical history, lifestyle behaviors, functional status and current medications were recorded, and blood and urine samples were collected. Estimated glomerular filtration rate (eGFR) was calculated by a modified three-variable equation. RESULTS: We enrolled 1138 patients, 69.6% of whom were male, with a mean age of 68 years. Compared with Western cohorts, patients in this study had a lower body mass index (BMI) and higher proteinuria. The prevalence of CVD was 26.8%, which was lower than that in Western cohorts but higher than that in the general Japanese population. Multivariate analysis demonstrated the following association with CVD prevalence: hypertension (adjusted odds ratio (aOR) 3.57; 95% confidence interval (CI) 1.82-7.02); diabetes (aOR 2.45; 95% CI 1.86-3.23); hemoglobin level less than 11 g/dl (aOR 1.61; 95% CI 1.21-2.15); receiving anti-hypertensive agents (aOR 3.54; 95% CI 2.27-5.53); and statin therapy (aOR 2.73; 95% CI 2.04-3.66). The combination of decreased eGFR and increased proteinuria was also associated with a higher prevalence of CVD. CONCLUSIONS: The participants in this cohort had a lower BMI, higher proteinuria and lower prevalence of CVD compared with Western cohorts. Lower eGFR and high proteinuria were associated with CVD prevalence. Prospective follow up of these study patients will contribute to establishment of individual population-based treatment of CKD.

Intracellular ClC-3 chloride channels promote bone resorption in vitro through organelle acidification in mouse osteoclasts.

ClC-7 Cl(-) channels expressed in osteoclasts are important for bone resorption since it has been shown that disruption of the ClCN7 gene in mice leads to severe osteopetrosis. We have previously reported that Cl(-) currents recorded from mouse osteoclasts resemble those of ClC-3 Cl(-) channels. The aim of the present study was to determine the expression of ClC-3 channels in mouse osteoclasts and their functional role during bone resorption. We detected transcripts for both ClC-7 and ClC-3 channels in mouse osteoclasts by RT-PCR. The expression of ClC-3 was confirmed by immunocytochemical staining. Mouse osteoclasts lacking ClC-3 Cl(-) channels (ClC-3(-/-) osteoclasts) derived from ClCN3 gene-deficient mice (ClC-3(-/-)) showed lower bone resorption activity compared with ClC-3+/+ osteoclasts derived from wild-type mice (ClC-3+/+). Treatment of ClC-3+/+ osteoclasts with small interfering RNA (siRNA) against ClC-3 also significantly reduced bone resorption activity. Electrophysiological properties of basal and hypotonicity-induced Cl(-) currents in ClC-3(-/-) osteoclasts did not differ significantly from those in ClC-3+/+ osteoclasts. Using immunocytochemistry, ClC-3 was colocalized with lysosome-associated membrane protein 2. Using pH-sensitive dyes, organelle acidification activity in ClC-3(-/-) osteoclasts was weaker than in ClC-3+/+ osteoclasts. Treatment of ClC-3+/+ osteoclasts with siRNA against ClC-3 also reduced the organelle acidification activity. In conclusion, ClC-3 Cl(-) channels are expressed in intracellular organelles of mouse osteoclasts and contribute to osteoclastic bone resorption in vitro through organelle acidification.

Study of the oral microbial flora in patients with renal disease.

AIM: The aim of this study is to bacteriologically investigate the oral environment in patients with renal disease and thereby reveal their influence on both caries and periodontal diseases. METHODS: The authors compared oral microbial flora between patients with renal disease (non-haemodialysis: n = 40, haemodialysis: n = 41) and healthy people (n = 62), and also between haemodialysis patients and non-haemodialysis patients in the disease group. Cariogenic bacteria were identified according to Dentocult System, whereas periodontal bacteria were identified using the polymerase chain reaction method. RESULTS: When comparing between patients with renal disease and healthy people, the detected number of cariogenic bacteria and the detection rates of the periodontal bacteria in the patients with renal disease were significantly higher than in healthy people (P < 0.05). When comparing the patients on haemodialysis with those not receiving it, no significant differences in the detected number of cariogenic bacteria were observed. However, the detection rates of periodontal bacteria were lower in patients on haemodialysis (P < 0.05). CONCLUSION: The findings suggest that patients with renal disease tend to have a high risk of dental caries and periodontal disease than the control.

CLC-3 deficiency leads to phenotypes similar to human neuronal ceroid lipofuscinosis.

BACKGROUND: CLC-3 is a member of the CLC chloride channel family and is widely expressed in mammalian tissues. To determine the physiological role of CLC-3, we generated CLC-3-deficient mice (Clcn3-/- ) by targeted gene disruption. RESULTS: Together with developmental retardation and higher mortality, the Clcn3-/- mice showed neurological manifestations such as blindness, motor coordination deficit, and spontaneous hyperlocomotion. In histological analysis, the Clcn3-/- mice showed a pattern of progressive degeneration of the retina, hippocampus and ileal mucosa, which resembled the phenotype observed in cathepsin D knockout mice. The defect of cathepsin D results in a lysosomal accumulation of ceroid lipofuscin containing the mitochondrial F1F0 ATPase subunit c. In immunohistochemistry and Western blot analysis, we found that the subunit c was heavily accumulated in the lysosome of Clcn3-/- mice. Furthermore, we detected an elevation in the endosomal pH of the Clcn3-/- mice. CONCLUSIONS: These results indicated that the neurodegeneration observed in the Clcn3-/- mice was caused by an abnormality in the machinery which degrades the cellular protein and was associated with the phenotype of neuronal ceroid lipofuscinosis (NCL). The elevated endosomal pH could be an important factor in the pathogenesis of NCL.