*3.2.3 Diabetes*

Many studies have shown that diabetes is a risk factor for VC in patients without CKD. In patients with eGFR <60 mL/min/1.73 m2 who were not on dialysis, diabetes also increased the risk of VC from 3.5 to 55.7% [114].

## *3.2.4 Dyslipidemia*

Dyslipidemia increases the risk of VC in patients without CKD, via induction of inflammation and endothelial/vascular smooth muscle cell damage by oxidized lipids [115, 116]. Beneficial effects of sevelamer on VC may be related to its lipidlowering effects [99].

#### *3.2.5 Other molecules*

Serum Gla-Rich Protein (GRP) levels were found to progressively decrease from stage 2 to stage 4 CKD. A multivariate analysis study identified that decreased eGFR, low levels of GRP, and high levels of fibroblast growth factor-23 (FGF-23) were associated with higher VC score and pulse pressure. These results indicate an association between GRP, renal dysfunction and CKD-mineral and bone disorder. The relationship between low levels of GRP and VC suggests a future potential utility for GRP as an early marker of vascular damage in CKD [117]. Once uremic CPPs and EVs are important players in the mechanisms of widespread calcification in CKD, GRP could have a role as an inhibitory factor, preventing calcification at systemic and tissue levels. Possible future approaches targeting the increase of γ-carboxylated GRP bioavailability could represent promising therapeutics [118].

#### **3.3 Detection**

The recognition of vascular or valvular calcification in patients with CKD stages G3a–G5D places them with highest cardiovascular risk [119]. The early diagnosis of VC and the identification of its cause raises hope for therapeutic intervention that might reduce CVD in patients with CKD.

Various noninvasive methods, such as ultrasound, fluoroscopy, and digital subtraction angiography, have been used to detect and measure VC [28]. Currently, EBCT and multidetector computed tomography (MDCT) are excellent methods to detect and quantify VC [28], with their results being stronger predictors of a cardiovascular event in normal population [28, 119]. Bursztyn and colleagues reported a twofold greater progression in coronary calcium score (measured by MDCT) in hypertensive patients with CKD, than in hypertensive patients with normal renal function [120].

A number of noninvasive methods, which are more easily and available techniques, can also be used to detect the presence or absence of valvular calcification, like lateral abdominal radiograph and echocardiogram [119]. The simplest technique is plain radiography, which demonstrates pipe-stem calcification of the tunica media and more irregular, patchy calcifications of the internal elastic lamina. However, this is an insensitive method and does not quantify the severity of VC [8].

Several scores, based on plain radiographic imaging or CT scans, are used in clinical studies to calcium quantification and scoring:


In the Study of Mineral and Bone Disorders that included 742 patients with nondialysis CKD stages 3–5 from 39 centers in Spain, VC assessment using Adragão Score was independently associated with all-cause and cardiovascular mortality as well as a shorter hospitalization event–free period [122].

• **Kauppila score** – This score quantifies the severity of lumbar aortic calcifications observed on a lateral abdominal radiograph ranging from the T-10 vertebra to the first two sacral vertebrae. A score of 1 to 3 is assigned based on extent of calcification (ie, one-third, two-thirds, or more than two-thirds of the vertebra).

## **3.4 Treatment**

The approach to decrease the progression of VC can be influenced by treatment. Given that VC is associated with increased cardiovascular risk and the pathogenesis seems to be related to CKD-MBD abnormalities and atherosclerosis, the treatment should focus on the prevention of arterial lesions, correcting the several traditional and non-traditional pro-atherogenic risk factors responsible for arterial injury, mainly calcium and phosphate balance [5, 29].

Some experimental studies have suggested that the administration of magnesium prevents VC, not only reducing the deposition of calcium, but also inhibiting osteogenic transdifferentiation, and may be considered an important and realistic approach to potentially reduce the risk for VC and subsequent cardiovascular complications in CKD patients. Clinical trials are warranted to further assess the clinical relevance of magnesium in this regard [123, 124].

*Vascular Calcification and Cardiovascular Risk in Chronic Kidney Disease: A Problem That Is… DOI: http://dx.doi.org/10.5772/intechopen.99886*

In patients with CKD G3a–G5D, decisions about phosphate-lowering treatment should be based on progressively or persistently elevated serum phosphate, as mentioned earlier [119].

In the management of moderate to severe secondary hyperparathyroidism, current treatment options consist of the oral administration of intestinal phosphate binders, oral or intravenous calcitriol or active vitamin D analogs, and the oral or intravenous calcimimetic agents (cinacalcet and etacalcetide) [125].
