Pro: Should we correct vitamin D deficiency/insufficiency in chronic kidney disease patients with inactive forms of vitamin D or just treat them with active vitamin D forms?

Evidence for the usefulness of using vitamin D to treat 'renal bone disease' is now nearly six decades old. In regular clinical practice, however, it is more like three decades, at most, that we have routinely been using vitamin D to try to prevent, or reverse, the impact of hyperparathyroidism on the skeleton of patients with chronic kidney disease (CKD). The practice has been in the main to use high doses of synthetic vitamin D compounds, not naturally occurring ones. However, the pharmacological impacts of the different vitamin D species and of their different modes, and styles of administration cannot be assumed to be uniform across the spectrum. It is disappointingly true to say that even in 2016 there is a remarkable paucity of evidence concerning the clinical benefits of vitamin D supplementation to treat vitamin D insufficiency in patients with stage 3b-5 CKD. This is even more so if we consider the non-dialysis population. While there are a number of studies that report the impact of vitamin D supplementation on serum vitamin D concentrations (unsurprisingly, usually reporting an increase), and some variable evidence of parathyroid hormone concentration suppression, there has been much less focus on hard or semi-rigid clinical end point analysis (e.g. fractures, hospitalizations and overall mortality). Now, in 2016, with the practice pattern changes of first widespread clinical use of vitamin D and second widespread supplementation of cholecalciferol or ergocalciferol by patients (alone, or as multivitamins), it is now, in my view, next to impossible to run a placebo-controlled trial over a decent period of time, especially one which involved clinically meaningful (fractures, hospitalisation, parathyroidectomy, death) end-points. In this challenging situation, we need to ask what it is we are trying to achieve here, and how best to balance potential benefits with potential harm.