Which Vitamin D in Chronic Kidney Disease: Nutritional or Active Vitamin D? Or Both?

As vitamin D insufficiency is very common world-wide, vitamin D supplementation has generated much debate and subsequent research not only in the general population but also in patients with chronic kidney disease (CKD). Several observational and mechanistic studies have suggested that vitamin D’s actions may be more broad and significant than originally appreciated, far exceeding bone and mineral metabolism. This is probably due to the fact that most tissues in the body express vitamin D receptors. As patients with kidney disease cannot convert 25-hydroxyvitamin D [25(OH)D] to its more active form, 1,25-dihydroxy vitamin D [1,25(OH)2D] because of reduced activity of the enzyme 1α-hydroxylase in the kidneys to produce classic bone and mineral effects, nephrologists have traditionally replaced patients with kidney disease with active vitamin D, 1,25-dihydroxvitamin D, or related analogs. Multiple observational studies in patients with CKD have shown that they not only have low levels of 1,25(OH)2D, but also low 25(OH)D levels. The fact that there is also extrarenal conversion of 25(OH) vitamin D to 1,25(OH)2 vitamin D in CKD in multiple tissues leading to autocrine effects, has led to the speculation that CKD patients should also need to be supplemented with nutritional vitamin D. This chapter outlines the available evidence on the controversy about which vitamin D is better for patients with kidney disease: Active vitamin D, nutritional or both.