Vitamin D-induced hypercalcemia in experimental renal failure.

Hypercalcemia was induced in 5/6 nephrectomized rats fed a low calcium diet by administering pharmacologic doses of vitamin D. The degree of hypercalcemia was greater in uremic rats than in sham-operated rats both of which were given vitamin D. Bone resorption was marked in both groups but differed in distribution. Increased osteoclasis in uremic rats was limited to diaphyseal cortical bone while metaphyseal trabeculae were relatively unaffected compared to sham-operated rats administered vitamin D. Ultrastructurally thyroid C cells were degranulated and in an active stage in both groups of rats receiving vitamin D. Urinary calcium excretion was greater in sham-operated rats given vitamin D than in uremic rats. The greater renal retention of calcium in uremic rats given vitamin D was felt to contribute to the development of hypercalcemia. These studies suggest that although trabecular bone was resistant to pharmacologic levels of vitamin D in renal failure, hypercalcemia developed due to selective resorption of cortical bone and impairment of renal calcium excretion.