Vitamin D and renal disease

The kidney is a central component of the powerful endocrine system that has evolved to maintain extracellular calcium and phosphate within narrow limits, a process vital for normal cellular physiology and skeletal integrity. Indeed, in the course of kidney disease, abnormalities in calcium, phosphate, parathyroid hormone (PTH), and vitamin D metabolism cause alterations in bone turnover, mineralization, volume, linear growth or strength, vascular and soft tissue calcifications, and high mortality rates. The integrity of the vitamin D endocrine system is important for human health, and this is suggested by the epidemiological association between vitamin D deficiency and a high risk for all causes of mortality in the general population. Normal kidney function is critical to maintain the health benefits of a normal vitamin D status, as demonstrated by almost 30 years of therapy directed to correct calcitriol deficiency in kidney disease. Clinical findings suggest and the high incidence of vitamin D deficiency in chronic kidney disease, the safe correction of vitamin D deficiency/insufficiency has become a high priority among nephrologists, and has posed important challenges regarding the adequacy of dosage and timing of current recommendations for vitamin D supplementation; efficacy of exclusive calcitriol therapy to fully compensate for autocrine VDR actions; the potential adverse effects of interventions with high doses of calcitriol and its analogs to aggravate vitamin D deficiency; and the safety and efficacy of the combined correction of 25(OH)D and calcitriol deficiency/insufficiency to maximize autocrine and endocrine VDR actions.