MO473INTERACTION OF SCLEROSTIN AND OSTEOPROTHERIN IN THE DEVELOPMENT OF VASCULAR CALCIFICATIONS AT STAGE 3-5 OF CHRONIC KIDNEY DISEASE
Authors: Dzgoeva Fatima 
Published: May 2021

Abstract

Background and Aims: Background and Aims: .
Vascular calcification (VC) due to bone-mineral metabolism disorders is a predictor of high cardiovascular mortality in patients with late-stage chronic kidney disease (CKD) . The established bone-vascular axis in CKD, which relates to interactions between changes in the bone and vascular systems that have similar mechanisms, allows bone metabolism inhibitors to act as potential risk factors for VC. Morphogenetic protein osteoprotegerin (OPG) and glycoprotein sclerostin are opposite inhibitors of bone metabolism: OPG inhibits osteoclastogenesis, sclerostin has an inhibitory effect on osteoblastogenesis. Although both proteins are recognized as high-risk factors for remodeling the heart and large arteries in patients with CKD, the mechanisms and possibilities for correcting these changes are not fully clear.
of the study was to investigate the mechanisms of the relationship between OPG and sclerostin in the development of cardiovascular complications due to calcification of the aorta and large arteries in the late stages of CKD.

Method: Method
The cross-sectional study included 105 patients with stage 3-5 CKD [49 men; 64.0 (23.0-76.0)years]. The glomerular filtration rate determined using the CKD-EPI equation was 38.4 (8.6–92.3) ml / min / 1.73 m2. The general clinical examination included assessment of hematopoiesis (hemoglobin, hematocrit, ferritin and transferrin), determination of total protein and albumin levels, cholesterol, electrolytes (sodium, potassium) in the blood, and indicators of nitrogen metabolism (creatinine, urea). Parameters of bone-mineral metabolism – parathyroid hormone (PTH), calcium, phosphorus, alkaline phosphatase of blood serum-were evaluated. The level of morphogenetic protein OPG and glycoprotein sclerostin was determined using commercial ELISA kit from Biomedica (Austria) by enzyme immunoassay. The morphofunctional features of the aorta and large arteries were studied by duplex scanning using the Doppler effect. We determined the peak systolic velocity of blood flow in the aortic arch (Vps-peak systolic velocity) , which indirectly indicates the state of the aortic wall and its lumen. Echocardiography with Doppler imaging was performed on the "ALOKA 4000" device. The LV myocardial mass index (LVMI), LV hypertrophy variants, LV systolic and diastolic function were determined.

Results
Cardiovascular damage, which manifests itself in the form of various variants of left ventricular hypertrophy, aortic rigidity, arteriosclerosis and vascular calcification, and directly correlated with the severity of renal failure, was detected in 86% of the examined patients with stage 3-5 CKD. The level of OPG and sclerostin in the blood serum increased with the progression of renal failure from the 3rd to the 5th. The main associations with Vps changes were high OPG levels [OR = 2.39 95% confidence interval (95% CI) (1.34–4.86) for levels ranging from 5.98 to 9.26 pmol / L and OR = 5.54 95% CI (2.64–13.5) for levels ≥9.26 pmol / L; P &lt;0.0001] and high sclerostin levels [OR = 2.64 95% CI (1.42–5.16) for levels ranging from 0.744 to 1.211 ng / ml and OR = 3.69 95% CI (1.76–7.31) for a level ≥1.211 ng / ml; P = 0.0001]. Thus, the logistic regression model showed that the risk of aortic calcification was significantly increased when both OPG (≥5.98 pmol / L) and sclerostin (≥0.744 ng / ml) levels were high [ uncorrected model: OR = 11.93 (4.54–25.2); P &lt;0.0001; on the model adjusted for generally recognized cardiovascular disease risk factors: OR= 5.55 (1.43–1914); P = 0.02].

Conclusion
The results suggest that bone metabolism inhibitors, OPG and sclerostin, are independently associated with aortic calcification with potential additive effects in patients with stage 3-5 CKD. The risk of vascular calcification was significantly increased when OPG and sclerostin levels were high