Background. Renal failure results in deficiency of active vitamin D₃ that has diverse effects on metabolism and organ functions. Treatment with active forms of vitamin D₃ ameliorates abnormalities in bone and mineral metabolism, cardiac function, immune response and others. We hypothesized that treatment with vitamin D₃ may be beneficial for survival in patients with end-stage renal disease (ESRD). Methods. We compared the risk of death between regular users (n = 162) and non-users (n = 80) of oral 1α-hydroxyvitamin D₃ (alfacalcidol) in a cohort of ESRD patients undergoing haemodialysis for a follow-up of 61 ± 23 months. The daily dose of alfacalcidol ranged from 0.25 to 1.5 μg, with a median of 0.5 μg. Results. The alfacalcidol users showed a lower risk of death from cardiovascular disease than the non-users in a univariate Cox model [hazards ratio (HR) 0.287, 95% confidence interval (CI) 0.127–0.649, P = 0.003], whereas the risk for death from non-cardiovascular disease was not different between the two groups. Stepwise multivariate Cox analysis showed that cardiovascular mortality was significantly associated with age, presence of diabetes mellitus and treatment with alfacalcidol (HR 0.377, 95% CI 0.246–0.578, P = 0.022). Conclusions. These results indicate that use of oral alfacalcidol was associated with reduced risk for cardiovascular death in this cohort of ESRD patients. The result of this observational study warrants further randomized controlled trials with 1α-hydroxy vitamin D₃ to confirm the possibility that such medication improves survival of ESRD patients.

Arterial stiffness affects cardiac functions, peripheral circulation, and cardiovascular mortality. We examined whether arterial stiffness in different regions is equally affected by diabetes and other factors. The subjects were 161 patients with type 2 diabetes and 129 healthy subjects comparable in age and sex. Arterial stiffness was evaluated by measuring pulse wave velocity (PWV) in the heart-carotid, heart-brachial, heart-femoral, and femoral-ankle segments using an automatic device. The diabetic patients had greater PWV than the healthy subjects in the four arterial regions, and the effect of diabetes on PWV was greater in the heart-carotid and heart-femoral segments (central) than in the heart-brachial and femoral-ankle regions (peripheral). PWV increased with age in the four arterial regions, and the effect of age on PWV was greater in the central than in peripheral arteries. In multiple regression analysis, age and systolic blood pressure had significant impacts on PWV of the four regions, whereas diabetes was significantly associated only with PWV of the central arteries. In contrast, sex was associated with PWV of the peripheral arteries. Thus, type 2 diabetes had greater impact on PWV of the central arteries, and different factors were involved in PWV among different arterial regions.

Summary: Background and objectives: Dialysis patients show “reverse causality” between serum cholesterol and mortality. No previous studies clearly separated the risk of incident cardiovascular disease (CVD) and the risk of death or fatality after such events. We tested a hypothesis that dyslipidemia increases the risk of incident atherosclerotic CVD and that protein energy wasting (PEW) increases the risk of fatality after CVD events in hemodialysis patients. Design, setting, participants, & measurements: This was an observational cohort study in 45,390 hemodialysis patients without previous history of myocardial infarction (MI), cerebral infarction (CI), or cerebral bleeding (CB) at the end of 2003, extracted from a nationwide dialysis registry in Japan. Outcome measures were new onsets of MI, CI, CB, and death in 1 year. Results: The incidence rates of MI, CI, and CB were 1.43, 2.53, and 1.01 per 100 person-years, and death rates after these events were 0.23, 0.21, and 0.29 per 100 person-years, respectively. By multivariate logistic regression analysis, incident MI was positively associated with non-HDL cholesterol (non–HDL-C) and inversely with HDL cholesterol (HDL-C). Incident CI was positively associated with non–HDL-C, whereas CB was not significantly associated with these lipid parameters. Among the patients who had new MI, CI, and/or CB, death risk was not associated with HDL-C or non–HDL-C, but with higher age, lower body mass index, and higher C-reactive protein levels. Conclusions: In this hemodialysis cohort, dyslipidemia was associated with increased risk of incident atherosclerotic CVD, and protein energy wasting/inflammation with increased risk of death after CVD events.