Vitamin D status is determined by the serum concentration of one of its metabolites, 25-hydroxy-D. Defining
vitamin D deficiency based on its classical roles in gut
calcium absorption and bone mineralization is problematic in dialysis patients and, until recently, was ignored in the nephrology literature. The newly recognized nonclassical functions of
vitamin D include effects on the immune system,
cardiovascular disease, and
cancer. The nonclassical effects are likely to be equally relevant in the dialysis population, but suffer from a lack of strong evidence on which to base therapeutic targets. Past medical opinion in the nondialysis population warned that higher dose
vitamin D supplementation may be toxic and was unnecessary. This is because older supplementation recommendations were based on early twentieth century studies using
cod-liver oil to treat
rickets. The clinical resolution of
rickets requires a relatively low dose of
vitamin D. Current
vitamin D guidelines generally target higher 25-hydroxy-D levels of 30 ng/ml, based on optimizing markers of bone health. This results in very high estimates of 50-100% for the prevalence of
vitamin D deficiency in dialysis patients. This review examines the relevance of data on the classical and nonclassical effects of
vitamin D in dialysis patients. An evidence-based dosing regimen for use in dialysis patients is suggested to safely and reliably achieve
vitamin D sufficiency.