Optimum route of administration of vitamin D in renal failure

Vitamin D preparations [1-alpha-hydroxycholecalcifol (1-alpha OHD3) or 1,25-dihydroxycholecalciferol (1,25(OH)2D3)] may be administered orally, subcutaneously, intraperitoneally or intravenously. They may be given daily, sometimes in divided doses, or intermittently in large bolus doses, usually three times per week. A further variable is the timing of administration, which may be at night when the gut calcium load is at a minimum. In at least some studies high dose intermittent bolus administration of vitamin D can reduce parathyroid hormone (PTH) secretion by a mechanism separated in time from an increase in ionized calcium (iCa2+). In addition, some but not all studies have shown an improvement in calcium set point and in parathyroid gland sensitivity to calcium. It is also clear from a number of studies that this treatment can succeed where conventional daily administration has failed. Bolus intravenous therapy is most conveniently given after haemodialysis treatment sessions. Bolus oral therapy, perhaps administered prior to sleep, may achieve a similar objective (PTH suppression without hypercalcaemia) in patients on continuous ambulatory peritoneal dialysis (CAPD). It is also becoming apparent that the parathyroid gland may yet again escape following bolus therapy. The success of bolus therapy may lie in several not mutually exclusive mechanisms: high peak concentrations of 1,25(OH)2D3 directly affecting the parathyroid gland, improved compliance, and a small but significant increase in plasma iCa2+. Further long-term controlled trials are needed before bolus therapy can be generally recommended.