Moderator's view: Vitamin D deficiency treatment in advanced chronic kidney disease: a close look at the emperor's clothes

Two recent vitamin D supplementation (ergocalciferol) trials in stage G5D CKD patients with vitamin D insufficiency showed that this sterol effectively increases serum 25-hydroxyvitamin D [25(OH)D] but fails to modify serum PTH and other clinical outcomes. The Pro side of this polar view emphasizes that the duration of these studies was too short to allow sensible analyses based on a clinical endpoint. Furthermore, he notes that in the second study, the use of active forms of vitamin D, phosphate binders and cinacalcet could have hindered appreciation of the effect of ergocalciferol supplementation per se The Con side produces an updated meta-analysis showing that inactive vitamin D forms largely fail to reduce serum PTH and affect various relevant endpoints, including muscle strength, functional capacity, quality of life and hospitalization. Studies suggesting an effect of inactive vitamin D forms in advanced CKD are either very small and mainly based on sequential, uncontrolled observations or inherently weak, simple pre/post studies. No biological or clinical evidence exists that 25(OH)D may exert meaningful effects in CKD patients who are being treated with active forms of vitamin D. Careful a etiologic studies based on the omics sciences, i.e. precise pathophysiological profiling of individual CKD patients followed by consequential, well-targeted intervention(s) in the precision medicine scenario, will likely provide a definitive answer to the lingering question of whether inactive vitamin D forms may have biological effects beyond those produced by their proximate metabolite 1,25-dihydroxyvitamin D3.