Vitamin D therapy in chronic kidney disease: back to the future?

Deficiency of 1,25(OH)2 vitamin D is inevitable in CKD, and is part of a cascade of bone and mineral abnormalities that result in secondary hyperparathyroidism. The widespread acceptance of calcitriol therapy as the treatment paradigm, has resulted in an overall neglect of vitamin D deficiency, as defined by low serum 25(OH)D levels Recent research has greatly enhanced our understanding of the disordered vitamin D metabolism seen in CKD. Furthermore vitamin D has been implicated in numerous disease states, beyond its traditional role in regulating bone and mineral metabolism. Low serum 25(OH)D levels have been linked to numerous adverse clinical outcomes in health and CKD. Additionally, the recognition of extra-renal, autocrine 1,25(OH)2D synthesis, present in many tissues, has refocused attention on the therapeutic potential of correcting low serum 25(OH)D levels. In this review we examine the physiology of disordered vitamin D metabolism in CKD, the clinical associations of low 25(OH)D levels in CKD, and discuss the rationale for vitamin D replacement in current clinical practice.