Pathogenesis of parathyroid dysfunction in end-stage renal disease

Abstract

The parathyroid functions to maintain normal calcium and phosphate homeostasis and is central to normal bone physiology. In end-stage renal disease (ESRD), there is a failure of these normal homeostatic mechanisms with the frequent development of secondary hyperparathyroidism, which contributes to the pathogenesis of renal bone disease. The phosphate retention of ESRD, together with the reduced serum calcium and 1,25-dihydroxycholecalciferol vitamin D(3) (1,25[OH](2)D(3)) concentrations are the known factors that determine the progression to secondary hyperparathyroidism. 1,25(OH)(2)D(3) markedly decreases parathyroid hormone (PTH) gene transcription, whereas the effects of calcium and phosphate are on PTH mRNA stability, PTH secretion, and parathyroid cell proliferation. The mechanisms of these effects are discussed in this review.