Biologic effects of 1,25-dihydroxycholecalciferol (a highly active vitamin D metabolite) in acutely uremic rats.
The development of a vitamin D-resistant state in the course of renal failure may be responsible for reduced intestinal absorption of calcium and an impaired response of skeletal tissue. Moreover, the kidney has been shown to carry out the conversion of 25-hydroxycholecalciferol (25-OH-CC) to a highly biologically active metabolite, 1,25-dihydroxycholecalciferol (1,25-diOH-CC). In the present studies, vitamin D-deficient rats, made acutely uremic by either bilateral nephrectomy or urethral ligation, received physiological doses of cholecalciferol (vitamin D(3)) (CC), 25-OH-CC or 1,25-diOH-CC; 24 hr later intestinal calcium transport, in vitro, and bone calcium mobilization, in vivo, were assessed. Whereas CC and 25-OH-CC stimulated calcium transport in sham-operated controls, they were without effect in the uremic animals. In contrast, administration of 1,25-diOH-CC stimulated calcium transport in both groups of uremic animals. Administration of 1,25-diOH-CC also stimulated calcium mobilization from bone in each group of animals. However, CC and 25-OH-CC were only effective in the sham controls and the uremic group produced by urethral ligation and had little or no effect in animals without kidneys. These results indicate that renal conversion of calciferol to a more biologically active form is necessary for the stimulation of intestinal calcium absorption and calcium mobilization from bone, and that 1,25-diOH-CC may bypass a possible defect in vitamin D metabolism in uremia. From these studies it is likely that uremia, per se, may also impair intestinal calcium transport.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001842:Bone and Bones / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002762:Cholecalciferol / Q000378:metabolism / Q000494:pharmacology*; D006887:Hydroxycholecalciferols / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects*; D008026:Ligation; D008297:Male; D009392:Nephrectomy; D051381:Rats; D014511:Uremia / Q000150:complications / Q000378:metabolism*; D014808:Vitamin D Deficiency / Q000209:etiology / Q000378:metabolism*
D006887:Hydroxycholecalciferols; D002762:Cholecalciferol; D002118:Calcium