**1. Introduction**

Vascular Calcification (VC) refers to the ectopic deposition of calcium phosphate crystals in arterial walls [1, 2]. This is a process that can be seen in all arteries with a distinction made based on the offended layer of the wall – medial or intimal – with different explaining mechanisms [3]. Besides vessel walls, other tissues like cardiac valves can also show calcifications [1, 4, 5].

In 1855, Virchow described the VC as "artery ossification", precisely in patients with renal disease [3, 6]. More recent, studies showed the same findings in Egyptian mummies [7].

In fact, with current molecular knowledge, we understand that mineralization of the tunica media, the type of VC associated with CKD and its mineral disturbances [8], occurs with trans-differentiation of muscle cells to bone cells, in a process one could call ossification [9, 10]. On the origin of those cellular changes, several factors interact to put in motion a series of events that will result in an active promotion of mineral deposition [1, 11, 12].

VC increases with age [13] and it is associated with many diseases such as diabetes [14], cardiovascular diseases (CVD) [8, 15], some genetic diseases [2, 16] and particularly CKD [8, 17–19]. In the latter, VC is observed in early stages, progresses with the renal impairment and affects almost every dialysis patient [20], even in the absence of traditional risk factors of hypertension, obesity, dyslipidaemia and smoking [21, 22]. For calcification to happen, an unregulated state of bone ossification induction and the loss of many molecules that are believed to be osteogenesis inhibitors, must occur [11, 12]. In CKD, the culprit appointed by many recent studies is another of its complications – the mineral disturbance [11].

Cardiovascular (CV) events are tightly related to the CKD population, with high incidence of sudden cardiac death, arrhythmia, congestive heart failure and stroke, corresponding to the most common cause of death, especially in dialysis patients [2, 20, 23]. VC progression and severity [24] is directly associated with these CV events and its related mortality [21] due to arterial calcification and its consequences, like ventricular hypertrophy or micro-embolic disease [10, 23, 25]. This explains the high prevalence of cardiac events and mortality even in patients without the traditional cardio-vascular risk factors [8, 10].

Until now, no study came to the conclusion that VC directly causes CV events [26]. Moreover, VC has some features in common with arterial aggression leading to CVD [26, 27]. For that reason, there are still some who argue that VC is a consequence and not the cause for CVD [28–30].

This chapter will focus on the biology of vascular calcification and the association with chronic kidney disease.
