Role of vitamin D deficiency in chronic kidney disease

Chronic kidney disease (CKD) has been recognized as a significant public health problem, with approximately 20 million Americans, or approximately 11% of the adult population, currently living with CKD. A significant source of morbidity associated with CKD is the development of disturbances of mineral metabolism, which occurs in virtually all patients during the progression of their disease, and is associated with bone loss and fractures, cardiovascular disease, immune suppression, and increased mortality. As kidney disease develops, there is decreased functional renal mass and a tendency to retain phosphorus. The reduction in functional renal mass and the retained phosphorus act to reduce renal 1alpha-hydroxylase activity and thus the renal production of calcitriol. Further compensation to maintain normal serum calcium and phosphorus homeostasis includes increased production and release of PTH and potentially other phosphaturic factors, such as fibroblast growth factor-23 (FGF23). This increase in FGF23 contributes to maintain normal serum phosphate independent of PTH but may worsen calcitriol deficiency by also inhibiting renal 1alpha-hydroxylase activity. The decrease in calcitriol also results in promoting further hyperparathyroidism and parathyroid gland hyperplasia, because calcitriol normally inhibits the production of prepro-PTH and parathyroid cell proliferation.