Traditional and Not Traditional Risk Factors in Appearance and Progression of Vascular Calcification in Haemodialysis Patients.

Cardiovascular diseases (CVD) are the main causes of death and hospitalization in patients affected by ESRD . The risk of death from CVD is already detectable in the early steps of chronic renal failure and it is from 20 to 30 times higher than in the general population. In ESRD patients the traditional risk factors for CVD do not offer a satisfactory explanation for such high mortality and morbidity rate. Among them, calcium-phosphate imbalance, inflammation, dialysis age, anaemia, hyperhomocysteinemia, oxidative stress, malnutrition, high lipoprotein levels and endothelial dysfunction have been considered (4).

Recently more attention has been paid to calcium phosphate imbalance involved either in the presence or the progression of vascular calcification (VC) in ESRD patients. Multiple factors have been noticed to contribute to VC other than mineral metabolism: the use of calcium-based phosphate binders, diabetes, aging, inflammation, cytokines and BMI.

Indeed it is now believed that arterial calcification is an active process that involves the phenotypic transformation of vascular smooth muscle cells (VSMC) into bone-forming osteoblast (ob)-like cells that are capable of expressing and/or release bone matrix proteins that are necessary to support the calcification process: OPG, RANKL, OPN, fetuin A and MGP. Several stimuli, first of all mineral changes have been shown to induce o modulate this phenotypic transformation. Indeed the expression and secretion of the above-mentioned proteins is regulated by several molecules such as TGF β, peroxisome proliferator-activated receptors (PPAR) γ, tumor necrosis factor (TNF) α.

Calcification develops at two sites in arterial wall, the intima and the media layers: 1)intimal calcification is frequent in advanced stages of atherosclerosis and is associated with plaque rupture and occlusion of the vessel;2)calcification of media layer, or Mockenberg's sclerosis, is observed in both capacitance vessels and in muscular vessels, it causes arterial stiffness and an high pulse pressure, and is an independent risk factor for mortality of ESRD patients.

Both types of calcifications have an important impact in terms of morbidity and mortality in patients with ESRD especially if the calcification pattern affects the coronary arteries.