New Vitamin D analogues for osteodystrophy in chronic kidney disease

Vitamin D therapy for patients with chronic kidney disease has until recently comprised alfacalcidol or calcitriol, both of which effectively attenuate secondary hyperparathyroidism and the target organ consequences thereof. Unfortunately, both these agents also have significant calcaemic and phosphataemic actions leading to frequent episodes of hypercalcaemia, hyperphosphataemia and an increase in the CaxP product. It is likely that these in turn have adverse effects on cardiovascular and survival outcomes by promoting soft tissue and vascular calcification. These drawbacks have fuelled a search for vitamin D compounds with a wider therapeutic window. Experimentally, some of these have exhibited remarkable dissociation between their ability to suppress parathyroid hormone (PTH) and concomitant calcaemic actions. In the case of 22-oxacalcitriol, the calcaemic potency relative to parathyroid suppression is 100th of that of calcitriol. 22-oxacalcitriol, with paricalcitol and doxercalciferol, are now widely used. Clinical studies of these agents, while confirming efficacy that is at least as good as alfacalcidol/calcitriol, have not consistently shown benefit in head to head comparison. Experience with these agents in the paediatric arena is very limited. One placebo-controlled study has now been completed in children-paricalcitol appeared effective and well tolerated. Calcimimetics, which simultaneously lower PTH, calcium and the CaxP product are about to enter the clinical arena-early studies in adults look promising, although they will need careful evaluation in children. These two therapies are likely to be additive and will probably complement one another effectively.