Effect of Uremic Sera on Parathyroid Hormone (PTH) Mediated Release of Calcium from Normal Rat Embryonal Bone Maintained in Tissue Culture

Abstract

Chronic renal failure is commonly associated with hypocalcemia but the mechanisms responsible for the sustained decrease in plasma ionized calcium are not clearly understood. Two major hypotheses have evolved to explain the hypocalcemia of chronic renal disease. Slatopolsky and Bricker attribute the decrease in ionized calcium in uremia to secondary hyperparathyroidism and retention of inorganic phosphorus (1). Massry and co-workers argue that hypocalcemia and secondary hyperparathyroidism occur independently of changes in serum inorganic phosphorus in acute and chronic renal failure (2). For Massry, altered Vitamin D metabolism resulting in a relative deficiency of 1,25 (OH)₂D₃ or other metabolites and skeletal resistance to calcemic action of parathyroid hormone are the principal determinants of hypocalcemia in renal failure. Other possible explanations for the hypocalcemia of uremia include an increased volume of distribution of ionized calcium due to increased transfer of calcium ions into cells and altered distribution of ionized calcium between bone extracellular fluid and plasma. It is likely that the hypocalcemia of renal failure is of multifactoral origin and that phosphorus retention, secondary hyperparathyroidism, deficiency of 1,25 (OH)₂D₃ and impaired skeletal response for calcium release to increase parathyroid hormone levels are contributing to the sustained hypocalcemia in uremia.