Vascular calcification in chronic renal failure.
The prevalence and extent of vascular calcification (VC) increases rapidly with time on dialysis. There is increasing evidence that medial calcification of conduit arteries, without intimal disease, is associated with important abnormalities of vascular compliance and increased risk of cardiovascular death. Coronary artery calcification is also common in end-stage renal disease, but further research is required to determine how much of this calcification is in the form of calcified intimal atherosclerotic plaque and how much in the tunica media. Calcific uraemic arteriolopathy causes a syndrome of ischaemic necrosis of the skin and subcutaneous tissue and appears to be increasing in incidence. At all sites, arterial calcification is a biologically controlled process, with expression in vascular smooth muscle cells of genes usually expressed in osteoblasts and the formation of hydroxyapatite. High extracellular phosphate concentration induces these phenotypic changes in vitro, and much of the clinical evidence supports hyperphosphataemia as the major driver of VC. Whether warfarin treatment plays a role, by inhibiting production of vitamin-K-dependent inhibitors of calcification in humans, remains uncertain but possible. High doses of prescribed calcium-based phosphate binders are associated with VC, whereas use of sevelamer to achieve the same serum phosphate level greatly retards progression of coronary and aortic calcification. The biological mechanism by which positive calcium balance and/or episodes of hypercalcaemia promotes VC remains unclear. Treatment of established calcific uraemic arteriolopathy consists of aggressive reduction of serum calcium x phosphate product; the roles of hyperbaric oxygen, steroid therapy, and non-warfarin anticoagulation remain uncertain.
Tomson
Charlie
C
South Mead Hospital, Westbury-on-Trym, Bristol, UK. Charlie.Tomson@north-bristol.swest.nhs.uk
D001158:Arteries / Q000473:pathology; D002114:Calcinosis / Q000145:classification / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D003952:Diagnostic Imaging; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy; D006435:Renal Dialysis / Q000009:adverse effects; D014652:Vascular Diseases / Q000145:classification / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*