Vitamin D and renal disease

In chronic kidney disease (CKD), the loss of renal capacity to maintain the integrity of the vitamin D endocrine system accelerates skeletal, immune, renal, and cardiovascular aging to increase mortality rates. This chapter updates the CKD-induced abnormalities in vitamin D bio-activation to 1,25(OH)2D, which compromise 1,25(OH)2D pro-survival actions and increase the risk of vitamin D toxicity. Focus is given to advances in CKD-driven impairment of 1,25(OH)2D-vitamin D receptor (VDR) complex pro-survival actions including (1) Suppression of parathyroid hormone (PTH) gene expression, parathyroid gland hyperplasia, and PTH-driven cardiovascular damage; (2) Attenuation of bone loss; (3) Induction of the fibroblast growth factor 23 (FGF23)/klotho axis; and (4) Attenuation of hypertension and systemic inflammation. This knowledge is essential to resolve controversies in evaluating vitamin D status during CKD and to identify biomarkers of 1,25(OH)2D/VDR action distinct from PTH to design personalized vitamin D interventions that safely and effectively delay CKD onset and/or attenuate its progression and complications.