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involved in the mechanisms of development and progression of VC involving mineralization of vascular
smooth muscle cells (VSMC) by phosphorus flux through sodium-dependent transporters, VSMC apoptosis.
Cell death in the vascular wall leads to development of cell membrane debris and apoptotic cells, which
can become the primary foci of apatite deposits. Increasing concentration of P and Ca, on the one hand,
leads to the growth of apatite crystals by passive precipitation, and on the other, can apparently activate
cellular and tissue mechanisms of calcification: suppressing differentiation of monocytes/macrophages in
osteoblast-like cells with increased FGF-23 levels and change in Klotho protein expression. Consequently,
hyperphosphatemia and rebalancing inducers and inhibitors of calcification, the presence of systemic
inflammation and oxidative stress contribute to the medial calcification in CKD. Osteogenic mechanisms
involve changes in the phenotype of vascular wall cells. Proteins characteristic for bone tissue (osteopontin,
osteocalcin, bone morphogenetic protein-2 (Run 2), as well as ectopic foci of typical bone and cartilage tissue
[51]
formation were found in VC foci .
[52]
A study of Kestenbaum , conducted among patients with CRF, showed that the presence of phosphorus in
the blood serum exceeding 3.5 mg/dL (1.13 mmol/L) was associated with a significant increase of mortality
risk, and for each increase of 1 mg/dL raised the risk of death by 18%.

The CKD Outcomes and Practice Patterns Study showed that hyperphosphatemia (PO4 > 6.1 mg/dL) was
[53]
associated with an increase in total and cardiovascular mortality by 1.18 .

In 10% of participants in the 15 years prospective study it was noted that the initial level of serum
[54]
phosphorus had a tight association with the calcification of the coronary arteries . A close correlation of
hyperphosphataemia and LVH has been identified, the development of which is a predictor of the CKD
patients mortality.

When assessing the effect of elevated levels of PTH and calcium-phosphate product on cardiovascular mortality,
[55]
Coen et al. concluded that the mortality of patients on LTH is higher due to non-traditional risk factors.

It was shown that hyperphosphatemia is an independent factor determining the unfavorable prognosis,
accelerating the progression of IHD, aggravating systolic hypertension and LVH, increasing the risk of
[56]
arrhythmia, as well as acute and congestive HF in patients on LTH .

DIABETES MELLITUS AND VC
Type 2 diabetes is one of the main independent risk factors for the development of cardiovascular pathology
[57]
that is the cause of death of more than 60% of patients with type 2 diabetes . In case of combined pathology
(diabetes and atherosclerosis), the vascular wall is subject to changes that lead to a decrease in the effective
lumen of the artery or thromboembolic complications.

However, in patients with diabetes in addition to atherosclerosis, calcification occurs. It was shown that the
[58]
intensity of calcification increases in cases of diabetes, as confirmed by Peter Lanzer et al. . Scientists have
concluded that Menkeberg sclerosis is x4.5 time more likely to be present in women and x1.8 in men with
diabetes than in individuals of appropriate age and sex who do not suffer from diabetes. Pathogenesis of VC
in diabetes is similar to pathogenetic processes occurring in CKD.

[59]
Ishimura et al. compared the factors influencing the calcification of peripheral vessels in patients on long-
term dialysis suffering from type 2 diabetes and without type 2 diabetes. It was revealed that the prevalence
of VC in patients with diabetes was higher than in patients without diabetes. DM often combines with