A B S T R A C T The effect of chronic renal disease on bone matrix and mineral maturation was evaluated in rats with experimental renal insufficiency of 2-11 wk duration utilizing bromoform-toluene gradient fractionation of bone powder, pulse labeling experiments with "5Ca and proline-'H differential extraction, an(d X-ray diffraction techniques.Maturation defects in both collagen and minieral (45Ca) metabolism were documented as early as 2 wk after the induction of uremia, when total bone calcium, inorganic phosphate, and hydroxyproline content were unchanged.The maturational defect progressed with advancing uremia despite insignificant changes in plasma pH and calcium, and normal bone carbonate levels.Although circulating levels of 25-hydroxycholecalciferol were significantly lower than normal in the uremic animals, pretreatment with either this vitamin D metabolite or vitamin D3 itself failed to alter the observed changes in skeletal maturation.
INTRODUCTIONChronic renal failure is attended by a metabolic acidosis, intestinal malabsorption of amino acids (1) and minerals, alterations in vitamin D3 metabolism as well as increased circulating levels of parathyroid hormone, and uremic toxins such as indoles and guanidines. These biological derangements either singularly or in concert result in a form of osteopenia which because of its varied histological manifestation is termed "renal osteodys-