Vascular calcification in chronic kidney failure: role of vitamin D receptor.
Chronic kidney disease (CKD) patients encounter an increased risk of cardiovascular disease and mortality compared with healthy individuals, most likely due to the presence of severe atherosclerosis and accelerated vascular calcification. Vascular calcification is an active, regulated process resulting from an imbalance between losses in inhibitory factors and gains in inducing factors present in cells and the blood circulation. However, exactly which inhibitory and inducing factors are involved remains unknown. The vitamin D receptor (VDR) is a nuclear receptor present in over 30 different tissues. Several VDR activators (VDRAs), including paricalcitol and calcitriol, are currently available for the treatment of secondary hyperparathyroidism in patients with CKD. Recent clinical observations demonstrate that VDRA therapy provides survival benefits for CKD patients in the order of paricalcitol > calcitriol > no VDRA therapy, independent of serum parathyroid hormone, phosphorus and calcium levels. The survival benefit of VDRAs seems contradictory to the perception that VDRAs, due to their potential impact of increasing serum phosphorus and calcium, may cause calcification in vessels. A review of the current literature shows that inconsistent data exist regarding the role of VDRAs in vascular calcification. A possible explanation is that the VDR may be involved in regulating several different pathways as an endocrine, paracrine and/or autocrine factor, and different VDRAs may have differential effects on the endocrine versus the paracrine/autocrine aspect.
Wu-Wong
J Ruth
JR
Abbott Laboratories, 100 Abbott Park Rd, Abbott Park, IL 60064, USA. ruth.r.wuwong@abbott.com
Melnick
Joel
J
D000818:Animals; D002114:Calcinosis / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D002117:Calcitriol / Q000627:therapeutic use; D004872:Ergocalciferols / Q000627:therapeutic use; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000503:physiopathology*; D018167:Receptors, Calcitriol / Q000502:physiology*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000627:therapeutic use
D004872:Ergocalciferols; D018167:Receptors, Calcitriol; D014807:Vitamin D; C084656:paricalcitol; D002117:Calcitriol