There is increasing evidence for health benefits accomplished by activated vitamin D through interaction with the vitamin D receptor (VDR) that go beyond calcium and bone homeostasis and regulation of parathyroid hormone (PTH) secretion. Treatment with vitamin D receptor agonists (VDRAs) is associated with reduced mortality in (pre)dialysis patients. Interestingly, these relations are independent of PTH levels and calcium x phosphorus product. This suggests the presence of biological functions of vitamin D that are independent of its interaction with the parathyroid glands. Because chronic kidney disease leads to increased cardiovascular mortality, mechanisms in which VDRAs can influence cardiovascular disease are discussed. These mechanisms comprise the potential ameliorating effects of VDRAs on atherosclerosis, arterial media calcification, cardiac hypertrophy, the renin-angiotensin system and thrombosis. Moreover, treatment strategies with VDRAs are discussed together with several recent observational studies. Treatment advice consists of correction of 25(OH) vitamin D deficiency, low-dose calcitriol in patients with secondary
hyperparathyroidism, and activated vitamin D analogues may be indicated when higher doses are needed to suppress PTH secretion. New insights into biological and clinical effects of VDRAs may broaden the patient group that may benefit from VDRA treatment to patients with creatinine clearances in the 30 to 60 ml/min range.