Lower Retinol Levels as an Independent Predictor of Mortality in Long-term Hemodialysis Patients: A Prospective Observational Cohort Study

Background: Malnutrition, inflammation, and oxidative stress are inter-related mechanisms linked to the progression of cardiovascular disease and prognosis of long-term hemodialysis (HD) patients. In this study, we focus on antioxidant vitamins and trace elements and the relationship of their serum levels to the prognosis of long-term HD patients. Study Design: Prospective observational cohort study. Setting & Participants: 261 long-term HD patients prospectively followed up for 5 years (20032008). The control group consisted of 66 healthy participants. Predictors: Retinol, alpha-tocopherol, retinol-binding protein 4 (RBP-4), and the trace elements zinc and selenium. Outcomes: Mortality and cardiovascular mortality. During follow-up, 146 patients (56%) died, and for 71 of these, death was due to cardiovascular causes. Measurements: Retinol, alpha-tocopherol, RBP-4, zinc, selenium, and basic nutritional and inflammatory parameters measured at the beginning of the study. Results: Retinol and RBP-4 levels were significantly increased, whereas retinol: RBP-4 ratio and alpha-tocopherol, selenium, and zinc levels were decreased in HD patients compared with controls (retinol, 0.017 +/- 0.006 mu g/dL in HD patients vs 0.010 +/- 0.002 mu g/dL in controls; P < 0.001). Lower retinol level was found to be a significant independent predictor of overall and cardiovascular mortality in multivariate Cox analysis (HR, 0.733 [95% CI, 0.599-0.896], P = 0.002, and 0.694 [95% CI, 0.511-0.942], P = 0.02, per 1 SD, respectively). The worst prognoses for patients with lower retinol levels were observed when these were combined with low albumin levels. Limitations: Sample size, investigation of prevalent, not incident, dialysis patients. Conclusions: This is the first study showing a lower retinol level as an independent predictor of overall and cardiovascular mortality in HD patients. It has to be elucidated whether the beneficial effects of higher serum retinol levels should be attributed to only better nutritional support or also to retinol's role in immune response and differentiation. Am J Kidney Dis 56: 513-521. (C) 2010 by the National Kidney Foundation, Inc.