Supplements confer benefits such as reduced mortality and improved parathyroid function.
Until relatively recently, little attention was given to a patient’s vitamin D status because it was assumed that with sun exposure, the skin could synthesize adequate amounts of the nutrient. But as TV viewing, video gaming, Internet surfing, and other indoor activities have surged in popularity, Americans are getting less sun.
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Recent studies have also shown that the previously accepted levels of adequate vitamin D are too low to optimize parathyroid hormone levels, which means that a larger proportion of people are classified as deficient than in the past. CKD and dialysis patients have the additional risk of inadequate levels of the renal enzyme for 1-hydroxylation of calcidiol, and thus cannot make the major active form of vitamin D, calcitriol.
Vitamin D supplements usually are not taken as single supplements but in combination with calcium and/or multivitamin mixtures. Mohamed Sekkarie, MD, at the Bluefield Regional Medical Center in West Virginia, measured the levels of calcidiol, calcitriol, and parathyroid hormone (PTH) in CKD patients (stages 3 and 4) in an outpatient nephrology clinic (Clin Nephrol. 2006;65:91-96). The measurements were obtained before the clinic’s physicians recommended vitamin D supplementation, so only 37 of the 108 patients in the study were taking supplements, usually in multivitamins. The vitamin D dose, typically 400 IU (5 µg), was accompanied by calcium, ranging from below 500-1,200 mg daily.
Supplements boost calcidiol
The researcher found that supplemented patients had higher calcidiol (31 vs. 17 ng/mL), calcitriol (21 vs. 16 pg/mL), and lower intact PTH (75 vs. 144 pg/mL) than those not taking a supplement. About 50% of the supplemented patients had adequate calcitriol compared with 10% of other patients. The supplemented group, however, included a higher proportion of patients below the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI) targets for PTH (20% vs. 8%), suggesting some patients were taking more vitamin D than needed.
In contrast, 66% of unsupplemented patients were above the PTH target compared with 21% of the supplemented patients. Because the latter group clearly had better vitamin D and PTH status than the non-supplemented group, the researcher suggested that routine supplementation with 400 IU over-the-counter vitamin D would be cost-effective, especially when testing for vitamin D is not feasible.
Patients with end-stage renal disease on hemodialysis require supplementation with vitamin D analogs because the lack of adequate functioning renal tissue limits the synthesis of calcitriol. There are three to choose from: calcitriol itself, doxercalciferol (1-hydroxy-vitamin D2), and paricalcitol (19-nor-1-a, 25-hydroxyvitamin D2). Both paricalcitol and doxercalciferol resemble calcitriol in their ability to lower PTH, but they have more modest effects on serum calcium and phosphorus concentrations.
Francesca Tentori, MD, and her colleagues at the University of New Mexico and Tufts New England Medical Center compared mortality after 37 months on hemodialysis of patients receiving one of the three forms of vitamin D (Kidney Int. 2006;70:1858-1865). Adjusted mortality rates were identical in patients on doxercalciferol (15.4 deaths/patient-years) and paricalcitol (15.3), and both were lower than on calcitriol (19.6). In all models tested, mortality was 20% higher for patients who did not receive any vitamin D treatment compared with those who did.
Because of the differences in effects of the analogs on calcium metabolism, the authors did an extensive analysis of serum levels of calcium, phosphorus, and PTH during the first three months of therapy. Levels of all three were lower in calcitriol patients compared with patients treated with the other two analogs.
After six months of treatment, compliance with KDOQI guidelines were similar in all three groups, whereas compliance with PTH guidelines was lower among calcitriol-treated patients. After six months, serum calcium was similar in all three groups. However, analysis of the data suggested that differences in calcium, phosphorus, and PTH were not likely to be associated with the differences in mortality between treatments. The authors hypothesized that possible differences in immunity or inflammation or both could be a factor.
Mitigating CVD
Dennis L. Andress, MD, of the VA Puget Sound Health Care System in Seattle, reviewed vitamin D in CKD (Kidney Int.2006;69:33-43), including evidence that vitamin D receptor activation evokes mechanisms that affect arterial calcification, atheroma formation, thrombogenesis, and cardiac dysfunction.
Activation of vitamin D receptors (VDR) by vitamin D therapy may directly mitigate cardiovascular disease by inhibiting the production of proteins that are either necessary for arterial mineralization or by stimulating proteins that inhibit mineralization. Calcitriol also inhibits circulating levels of IL-1b and IL-6, which are not only implicated in calcification but have important roles in mediating the inflammatory response to atheroma formation. An additional mechanism of VDR activation is preventing thrombosis.
Overall, the studies reviewed here show that vitamin D has beneficial effects not only on parathyroid function and bone density, but also on CVD. Clearly, a healthy vitamin D status is important to reduce mortality, but the best form of the vitamin for CKD and dialysis patients has yet to be determined.
