Use of active vitamin D sterols in patients with chronic kidney disease, stages 3 and 4.

This paper reviews randomized controlled trials and other reported data on the use of the active vitamin D sterols, such as calcitriol, alfacalcidol, and doxercalciferol, in the management of secondary hyperparathyroidism in patients with mild-to-moderate renal insufficiency (stage 3 or 4 chronic kidney disease). Data on potential benefits, including improved histologic abnormalities of bone from secondary hyperparathyroidism, increased bone mineral density, and a reduction of elevated parathyroid hormone levels, are documented. Consideration is given to the risks of such therapy, which include the production of hypercalcemia, more rapid progression of renal insufficiency, the induction of adynamic bone "disease," and accelerated vascular and soft tissue calcification. The low therapeutic index, or "benefit/risk ratio" of calcitriol and alfacalcidol, the sterols currently licensed for such treatment, is recognized. It is recommended that phosphate-restricted diets, phosphate-binding agents, and oral calcium supplements be given adequate trials before starting calcitriol or alfacalcidol. If PTH levels cannot be controlled by these measures, initial doses of these sterols and the proper surveillance during treatment are given. It is emphasized that the risks of hypercalcemia are likely to increase as the degree of kidney failure worsens. Further research using the "less calcemic" vitamin D sterols is clearly needed.