AimsDialysis patients experience an excess mortality, predominantly of sudden cardiac death (SCD). Accumulating evidence suggests a role of vitamin D for myocardial and overall health. This study investigated the impact of vitamin D status on cardiovascular outcomes and fatal infections in haemodialysis patients.Methods and results25-hydroxyvitamin D [25(OH)D] was measured in 1108 diabetic haemodialysis patients who participated in the German Diabetes and Dialysis Study and were followed up for a median of 4 years. By Cox regression analyses, we determined hazard ratios (HR) for pre-specified, adjudicated endpoints according to baseline 25(OH)D levels: SCD (n = 146), myocardial infarction (MI, n = 174), stroke (n = 89), cardiovascular events (CVE, n = 414), death due to heart failure (n = 37), fatal infection (n = 111), and all-cause mortality (n = 545). Patients had a mean age of 66 ± 8 years (54% male) and median 25(OH)D of 39 nmol/L (interquartile range: 28–55). Patients with severe vitamin D deficiency [25(OH)D of≤ 25 nmol/L] had a 3-fold higher risk of SCD compared with those with sufficient 25(OH)D levels >75 nmol/L [HR: 2.99, 95% confidence interval (CI): 1.39–6.40]. Furthermore, CVE and all-cause mortality were strongly increased (HR: 1.78, 95% CI: 1.18–2.69, and HR: 1.74, 95% CI: 1.22–2.47, respectively), all persisting in multivariate models. There were borderline non-significant associations with stroke and fatal infection while MI and deaths due to heart failure were not meaningfully affected.ConclusionSevere vitamin D deficiency was strongly associated with SCD, CVE, and mortality, and there were borderline associations with stroke and fatal infection. Whether vitamin D supplementation decreases adverse outcomes requires further evaluation.

Background. Patients on maintenance haemodialysis treatment experience an excessive risk of cardiovascular disease and mortality. The vitamin A concentration is known to be higher in these patients compared to the general population where elevated vitamin A concentrations are associated with adverse outcome. The impact of vitamin A on morbidity and mortality in end-stage renal disease patients is controversial and is the topic of this study. Methods. We analysed plasma retinol and retinol-binding protein 4 (RBP4) in 1177 diabetic haemodialysis patients, who participated in the German Diabetes and Dialysis Study (median follow-up 4 years). By Cox regression analyses hazard ratios (HRs) were determined for pre-specified, adjudicated end points according to baseline concentrations.Results. Patients had a mean age of 66 6 8 years, mean retinol and RBP4 concentrations of 3.28 (0.71-7.44) and 4.02 (1.28-10.1) lmol/L, respectively. Patients with retinol concentrations in the first quartile (<2.6 lmol/L) had an almost 2-fold increased risk of all-cause mortality compared to patients of the fourth quartile [>3.9 lmol/L; HR 1.81, 95% confidence interval (CI) 1.43-2.30]. There was a strong association between low retinol and the risk of sudden cardiac death (SCD, HR 2.22, 95% CI 1.41-3.50) and fatal infection (HR 2.19, 95% CI 1.26-3.82). Patients with RBP4 concentrations in the lowest quartile (<3.0 lmol/L) were more likely to die of any cause (HR 1.43, 95% CI 1.14-1.80), experience SCD (HR 1.97, 95% CI 1.28-3.03) and cardiovascular events (HR 1.43, 95% CI 1.10-1.85). Conclusion. This large cohort study shows a strong association of low retinol and RBP4 concentrations with SCD and all-cause mortality in diabetic haemodialysis patients.

Type 1 diabetes is associated with the presence of inflammation, which in turn affects parameters used to assess the vitamin A status. In the present study, we evaluated the influence of inflammatory status on retinol, retinol-binding protein 4 (RBP4), and transthyretin (TTR) in children and adolescents with type 1 diabetes. A total of 40 children with type 1 diabetes (median age, 14.2 y; median BMI-SDS, 0.53; median diabetes duration, 5.8 y; median HbA 1c , 7.3%) and 46 healthy subjects (median age, 12.8 y; median BMI-SDS, 0.34; median HbA 1c 5.4%) were recruited. Serum levels of CRP were significantly elevated (p ϭ 0.005) and retinol concentrations were significantly lower (p ϭ 0.02) in children and adolescents with type 1 diabetes compared with healthy subjects. Serum RBP4 and TTR showed no differences between the groups. Healthy children with CRP levels above 0.6 mg/L had significant lower levels of retinol (p ϭ 0.03). This was not observed in children with type 1 diabetes. The results suggest that, in contrast to healthy children, minor CRP elevation does not affect vitamin A transport complex in serum of children with type 1 diabetes. (Pediatr Res 62: 741-745, 2007)

SummaryBackground and objectives Trials with the antioxidant vitamin E have failed to show benefit in the general population. Considering the different causes of death in ESRD, this study investigated the association between plasma concentrations of a-tocopherol and specific clinical outcomes in diabetic hemodialysis patients.Design, settings, participants, & measurements In 1046 diabetic hemodialysis patients (participants of the German Diabetes and Dialysis Study), a-tocopherol was measured in plasma by reversed-phase HPLC. By Cox regression analyses, hazard ratios were determined for prespecified end points according to baseline plasma a-tocopherol levels: sudden death (n=134), myocardial infarction (n=172), stroke (n=89), combined cardiovascular events (n=398), fatal infection (n=107), and all-cause mortality (n=508).Results Patients had a mean age of 6668 years, and mean plasma a-tocopherol level was 22.869.6 mmol/L. Levels of a-tocopherol were highly correlated to triglycerides (r=0.63, P,0.001). Patients in the lowest a-tocopherol quartile had (in unadjusted analyses) a 79% higher risk of stroke and a 31% higher risk of all-cause mortality compared with patients in the highest quartile. The associations were attenuated after adjustment for confounders (hazard ratio stroke =1.56, 95% confidence interval=0.75-3.25; hazard ratio mortality =1.22, 95% confidence interval=0.89-1.69, respectively). There was no association between a-tocopherol and myocardial infarction, sudden death, or infectious death.Conclusions Plasma a-tocopherol concentrations were not independently associated with cardiovascular outcomes, infectious deaths, or all-cause mortality in diabetic hemodialysis patients. The lack of association can partly be explained by a confounding influence of malnutrition, which should be considered in the planning of trials to reduce cardiovascular risk in dialysis patients.

OBJECTIVEBMI and albumin are commonly accepted parameters to recognize wasting in dialysis patients and are powerful predictors of morbidity and mortality. However, both parameters reveal limitations and may not cover the entire range of patients with wasting. The visceral protein transthyretin (TTR) may be helpful in overcoming the diagnostic and prognostic gap. Therefore, the aim of this study was to assess the association of TTR with morbidity and mortality in hemodialysis patients.RESEARCH DESIGN AND METHODSThe TTR concentration was determined in plasma samples of 1,177 hemodialysis patients with type 2 diabetes. Cox regression analyses were used to determine hazard ratios (HRs) for the risk of cardiovascular end points (CVEs) and mortality according to quartiles of TTR concentration for the total study cohort and the subgroups BMI ≥23 kg/m2, albumin concentration ≥3.8 g/dL, and a combination of both.RESULTSA low TTR concentration was associated with an increased risk for CVE for the total study cohort (HR 1.65 [95% CI 1.27–2.14]), patients with BMI ≥23 kg/m2 (1.70 [1.22–2.37]), albumin ≥3.8 g/dL (1.68 [1.17–2.42]), and the combination of both (1.69 [1.13–2.53]). Additionally, a low TTR concentration predicted mortality for the total study cohort (1.79 [1.43–2.24]) and patients with BMI ≥23 kg/m2 (1.46 [1.09–1.95]).CONCLUSIONSThe current study demonstrated that TTR is a useful predictor for cardiovascular outcome and mortality in diabetic hemodialysis patients. TTR was particularly useful in patients who were not identified to be at risk by BMI or albumin status.