Vitamin D and Renal Disease

In chronic kidney disease (CKD), the progressive loss of renal capacity to maintain the functional integrity of the vitamin D endocrine system is a major determinant of the skeletal, renal, and cardiovascular damage that markedly increases mortality rates.This chapter updates the progress in our understanding of the pathophysiology underlying CKD-induced abnormalities in the systemic and local vitamin D bioactivation to its hormonal form, 1,25-dihydroxyvitamin D or calcitriol. Special focus is directed to the molecular bases to maximize the prosurvival actions of the calcitriol/vitamin D receptor complex in CKD beyond the suppression of the PTH gene and parathyroid cell growth including: (1) The attenuation of bone loss and vascular calcification unrelated to the control of secondary hyperparathyroidism; (2) The induction of the fibroblast growth factor 23 to prevent the proaging effects of hyperphosphatemia and of an excess of active vitamin D, and (3) The simultaneous induction of the klotho gene and inhibition of its two main downregulators, hypertension, and systemic inflammation to maintain the skeletal, renal, and cardiovascular protection conferred by renal and circulating klotho.