Vitamin D Status and Mortality Risk in CKD: A Meta-analysis of Prospective Studies

Background: Vitamin D deficiency, assessed as low 25-hydroxyvitamin D (25[ OH] D) level, is highly prevalent in patients with chronic kidney disease (CKD) and is associated with various adverse health outcomes. Whether low 25(OH) D levels in patients with CKD are an independent risk factor for mortality remains to be studied in detail, and this was the objective of our work. Study Design: A systematic review and meta-analysis of prospective observational studies. Setting & Population: Patients with CKD. CKD was diagnosed mainly as decreased estimated glomerular filtration rate. Selection Criteria for Studies: We performed a systematic literature search in MEDLINE, ISI, and EMBASE to identify prospective studies reporting on 25(OH) D levels and mortality. Predictor: 25(OH) D serum concentrations. Outcome: All-cause mortality. Results: 10 studies with an overall sample of 6,853 patients with CKD were included. Relative risk of mortality per 10-ng/mL (25-nmol/L) increase in 25(OH) D level was 0.86 (95% CI, 0.82-0.91), with no indication of publication bias or significant heterogeneity (I-2 = 15%; P = 0.3). Summary estimates for CKD cohorts with and without dialysis treatment showed homogeneous results (P = 0.9). Limitations: Results may be limited by heterogeneity, unconsidered confounders, and the observational design of the studies. Furthermore, publication bias by unpublished null findings on the association of 25(OH) D level and mortality cannot be ruled out and ascertainment of CKD was based largely on estimated glomerular filtration rate. Conclusions: Higher 25(OH) D levels are associated with significantly improved survival in patients with CKD. Whether treatment of low 25(OH) D level using natural vitamin D supplementation improves survival in patients with CKD remains to be elucidated in randomized controlled trials. Am J Kidney Dis. 58(3): 374-382. (C) 2011 by the National Kidney Foundation, Inc.