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 (I² =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 Furthermore, publication bias by unpublished null findings on the association of 25(OH)D level and mortality cannot be ruled out and ascertainment of CKD was based largely on estimated glomerular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.