25-hydroxyvitamin D in Chronic Kidney Disease

The effect of ergocalciferol and cholecalciferol on bone disease and overall health in chronic kidney disease (CKD) is a topic of interest to the nephrology community. A recent review published in the American Journal of Kidney Diseases discusses this from a practice guidelines standpoint. Co-author Dr. Ishir Bhan (IB) reviews this with Dr. Tejas Desai (eAJKD), eAJKD advisory board member.

eAJKD: What is the difference between ergocalciferol and cholecalciferol?

IB: Cholecalciferol is the native animal form of vitamin D that your body makes from cholesterol when your skin is exposed to ultraviolet light. Ergocalciferol is a plant-based vitamin D. Most nutritional supplements have historically contained ergocalciferol in the United States, but that’s changed over the years. The over-the-counter supplements contain cholecalciferol (400 IUnits- 2000 IUnits).  Most of what one gets in prescription form is ergocalciferol (the 50,000 unit pill). There is some literature to suggest that cholecalciferol is more potent than ergocalciferol.

eAJKD: Are there any limitations to high-dose ergocalciferol or cholecalciferol in late stage CKD patients?

IB: The same side effects that you would see in the general population are what you would likely see in CKD patients. I think this risk is often overstated, but certainly there have been cases where individuals have taken high-dose ergocalciferol or cholecalciferol in excessive amounts leading to hypercalcemia.  This complication is rare with commonly prescribed regimens. We recommend in our paper that individuals deficient in vitamin D (25-hydroxyvitamin D <30 ng/mL) receive a course that’s become popular, 50,000 units of ergocalciferol weekly for eight weeks.  This is usually enough to replete patients without the toxicity reported in the literature.

It is important to emphasize that with the kind of regimens we describe in the paper, the risk of toxicity is really quite low.

eAJKD: Based on your work, how should clinicians approach treating vitamin D deficiency in CKD patients ?

IB: The answer is easier for predialysis CKD where good evidence exists to suggest supplementing vitamin D deficient patients may help control secondary hyperparathyroidism. This is probably the most reliable association that’s been described in patients with CKD. A corollary is the uncertainy of whether correcting the secondary hyperparathyroidism is beneficial at all? That’s an ongoing topic of study. There’ve been a number of studies looking at associations of hyperparathyroidism with various outcomes that seem to suggest patients with severe secondary hyperparathyroidism are certainly at risk for bone disease, but other adverse outcomes as well. But those links are not as robust as one might hope for a big treatment effect.

eAJKD: Can you comment on the bioavailability of vitamin D in African Americans versus Caucasians?

IB: African Americans tend to have lower vitamin D levels and lower 25-hydroxyvitamin D levels, likely due to skin pigmentation. The endogenous synthesis of vitamin D depends on ultraviolet exposure.  This is limited in pigmented individuals where some of that ultraviolet light is absorbed by melanin, and unavailable for the conversion of cholesterol to vitamin D leading.

Vitamin D circulates in large part bound to a vitamin D binding protein, and this protein might be serving as a modulator for the total amount of vitamin D.  It appears that African Americans have lower total levels of 25-hydroxyvitamin D, but also lower levels of vitamin D binding protein. In other words, the actual bioavailable levels are not quite as different from Caucasians. While African American patients tend to be more vitamin D deficient, they have actually lower risks of fractures and tend to have higher bone density. Certainly, this area needs more robust studies.

To view the article abstract or full-text (subscription required), please visit AJKD.org.

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