Vitamin D status in both the general and CKD populations is a topic of major interest. In the general population, insufficient or deficient serum 25-hydroxvitamin D—25(OH)D—concentrations are associated with increased risk of cardiovascular disease, cancer, and mortality.
Similarly, in the CKD population, low levels of vitamin D are associated with poor outcomes. Patel et al (Kidney Int. 2010;77:715-720) describes evidence of vitamin D deficiency associated with anemia and Mehrotra et al (Kidney Int. 2009;76:977-983) found that CKD patients with serum 25(OH)D concentrations less than 15 ng/mL have a 56% increase in all-cause mortality risk.
The prevalence of 25(OH)D insufficiency (serum levels of 15-30 ng/mL) and deficiency (serum levels less than 15 ng/mL) in the CKD population has been estimated at 70%-86% (Am J Nephrol. 2004;24:503-510). The cause of reduced serum concentrations is multifactoral. Cholecalciferol or vitamin D3 is formed in the skin via sunlight exposure or is absorbed from ingested foods high in the vitamin.
Ergocalciferol, or vitamin D2, comes from a synthetically manufactured supplement. The amount of sun exposure needed for an individual to reach their daily requirement of D3 varies by the amount of melanin in the skin, whether sunscreen is used, the season of the year, and their location relative to the equator. Patients living in northern countries are at greater risk for low 25(OH)D concentrations. Rucker et al (J Nephrol. 2009;22:75-82) found that 93% of Canadian CKD patients studied were insufficient or deficient in 25(OH)D. The same author demonstrated previously that season can have a significant impact on vitamin D concentrations. In the summer, 68% of CKD patients had 25(OH)D concentrations less than 32 ng/mL, whereas in the winter 86% were below this level (CMAJ. 2002;166:1517-1524).
Sources of vitamin D
The level of adequate dietary intake (AI) for D3 established by the National Academy of Science is the amount to be ingested regardless of sun exposure. Daily AI varies by age. The AI is 400 IU/day for individuals aged 51-70 years and 600 IU/day for those older than 70 years (http://fnic.nal.usda.gov/). Vitamin D is fat soluble, so foods containing high amounts of vitamin D are often high in fat. For this reason, the vitamin D in fortified milk may be better absorbed by the body if the milk contains fat (e.g., 1% or greater). Other foods high in vitamin D are fatty fish, such as salmon or sardines, and eggs. These foods are not only excellent sources of good fats such as omega 3 fatty acids, but they are high in protein and other nutrients such as iron. Consequently, these foods should be mentioned when educating patients with end-stage renal disease (ESRD). Many foods are being fortified with vitamin D, calcium, and other micronutrients, but ESRD patients must be cautious because these foods may also contain phosphate additives.
Active vitamin D formation
The formation of active vitamin D, or 1,25(OH)2D, is accomplished via a two-step process. Of particular importance is the regulation by calcium and phosphate concentrations. Initially, 1,25(OH)2D is hydroxylated in the liver at the 25th carbon, while the kidneys produce 1-α-hydroxylase for the final conversion at the first carbon. Decreased calcium concentrations stimulate production of both parathyroid hormone (PTH) and 1-α-hydroxylase. However, elevated phosphorus concentrations counteract this by inhibiting 1-α-hydroxylase production and causing the parathyroid gland to become more resistant to calcium concentration fluctuations. Therefore, regulation of phosphorus through dietary restrictions and phosphate binders aids in the prevention of secondary hyperparathyroidism.
Researchers recently discovered FGF-23, a signaling molecule critical in regulating phosphate concentrations. In early stages of CKD, FGF-23 increases renal and gastrointestinal phosphate excretion, thereby keeping serum phosphate concentrations within the normal range and preventing the inhibition of 1-α-hydroxylase production and the stimulation of PTH (Clin J Am Soc Nephrol. 2010;5:1-6).
Nutritional interventions effective in regulating vitamin D metabolism include providing extensive education to CKD patients early in their disease course on foods that are high in vitamin D but low in phosphorus, the use of phosphate binders, and the importance of taking renal-specific multivitamins that do not contain phosphorus.
Vitamin D supplementation appears to pose little to no risk and may prevent patients from having insufficient or deficient 25(OH)D concentrations. Supplementation can be accomplished with either ergocalciferol or cholecalciferol. The optimal daily dose of oral vitamin D to prevent low values has yet to be identified through randomized clinical trials. However, in patients with serum levels in the insufficient range, guidelines from the National Kidney Foundation’s Kidney Disease Outcome Quality Initiative suggest 50,000 IU per month. For mild and severe deficiency, the recommendation is 50,000 IU/week for four and 12 weeks, respectively (http://www.kidney.org/professionals/kdoqi/guidelines_bone/index.htm).
It should be noted that these recommendations are based on expert opinion, and not a high-level of scientific evidence.