Pathogenesis of secondary hyperparathyroidism

Secondary hyperparathyroidism is a universal complication in patients with chronic renal failure. Hyperplasia of the parathyroid glands is typically s een in these patients. In early renal failure, alteration in vitamin metabo lism, decreased levels of calcitriol and moderate decreases in ionized calc ium may allow greater synthesis and secretion of PTH. As the disease progre sses, there is a decrease in the number of vitamin D receptors (VDR) and ca lcium receptors (CaR). The decreased number of VDR and CaR makes the parath yroid glands more resistant to calcitriol and calcium. Phosphorus induces h yperplasia of the parathyroid glands independent of calcium and calcitriol, and by a post-transcriptional mechanism increases PTH synthesis and secret ion. Experimental work in uremic rats demonstrated that if the animals are fed a high-phosphorus diet, they not only developed secondary hyperparathyr oidism but parathyroid cell hyperplasia. If the diet is then reduced in pho sphorus, the levels of PTH return to normal. However, the parathyroid cell hyperplasia persists and no apoptosis is seen. Thus, the control of the thr ee most important factors, calcium, calcitriol and phosphorus, is critical to prevent the development of secondary hyperparathyroidism and hyperplasia of the parathyroid glands.