Aim. To clarify the mechanisms of the effect of osteoprotegerin (OPG) and sclerostin on vascular calcification and the state of the cardiovascular system in chronic kidney disease (CKD). Materials and methods. A total of 110 patients aged 18 to 65 years with CKD stages 35D were examined. OPG, sclerostin, intact parathyroid hormone, and serum troponin I were determined using the commercial "Enzyme-linked Immunosorbent Assay Kit for Sclerostin" from Cloude-Clone Corp. (USA) by enzyme-linked immunosorbent assay. Results. An increase in sclerostin and OPG levels was revealed, which significantly correlated with a decrease in glomerular filtration rate, as well as an increase in left ventricle myocardial mass index and peak systolic blood flow in the aortic arch. Conclusion. Changes in the regulation of bone-mineral metabolism, in which the proteins inhibitors of bone metabolism, OPG and sclerostin, as well as the interactive interaction between the vascular and skeletal systems, play a decisive role in the development of lesions of the cardiovascular system caused by vascular calcification in CKD.
BACKGROUND. Cardiovascular complications caused by vascular calcification in chronic kidney disease (CKD) are closely related to disorders of bone and mineral metabolism, the mechanisms of which require further study.THE AIM: to clarify the role of the regulatory proteins of bone metabolism of sclerostin and osteoprotegerin in the processes of vascular calcification and the development of cardiovascular complications in CKD.PATIENTS AND METHODS. 110 patients with stage 3-5D CKD (67 men) were examined. Median age is 47.0 (23.0-68.0) years. Osteoprotegerin (OPG), sclerostin, intact parathyroid hormone (IPTG), troponin I in blood serum were determined using commercial kits "Enzyme-linked Immunosorbent Assay Kit for Sclerostin" ("Cloud-Clone Corp.", USA) and commercial kits "ELISA kit" ("Biomedica" (Austria) by enzyme immunoassay (ELISA). Echocardiography with Dopplerography was performed on the device "ALOKA 4000" ("Toshiba", Japan). The left ventricular myocardial mass index (LVMI) and peak systolic blood flow velocity in the aortic arch (Vps, peak systolic velocity) were determined to quantify hemodynamic changes indirectly indicating the state of the aortic vascular wall.RESULTS. Analysis of the ratios of the calculated glomerular filtration rate (EGFR), IMLJ, Vps, OPG, and sclerostin showed that a decrease in excretory kidney function is accompanied by an increase in the concentrations of OPG and sclerostin in the blood serum. At the same time, there is an increase in IMLJ and Vps. During the correlation analysis, it was shown that the level of OPG was positively correlated with the level of sclerostin and negatively with the level of iPTG.CONCLUSION. In our study, we obtained data confirming the interactive interaction between the vascular and bone systems. Morphogenetic proteins-inhibitors of bone metabolism (sclerostin and OPG) play a significant role in the defeat of the cardiovascular system in patients with CKD, as they promotes the development of vascular calcification.
Background and Aims Clinical studies in recent years have revealed a close relationship between hormonal disorders in women with CKD and the duration and quality of life, bone mineral and related disorders of the cardiovascular system. In individual studies, there is a tendency to improve the indicators of mineral and bone metabolism and the state of the cardiovascular system in hormonal or other drug-induced correction of hormonal dysfunctions in women. - Aims to study the effect of estrogen deficiency on bone and mineral metabolism in a population of women suffering from CKD stages III-V Method The study included 52 women who met the clinical criteria for the possible appointment of hormone therapy (both replacement and combined oral contraceptives) for the purpose of a detailed examination of the state of their cardiovascular system and bone-mineral metabolism in dynamics (with an interval of 10-12 months) in order to assess the degree of influence of estrogen-deficient conditions on the course of such common complications of CKD as cardiovascular diseases and pathology of the bone system. The age of the patients ranged from 26 to 61 years (mean age-50.65±9.17 years). The duration of CPN averaged 77.02 months.. The stages of CKD were determined according to the K/DOQI (2012) criteria, and the glomerular filtration rate was calculated using the CKD-EPI formula. The following parameters were evaluated: the concentration of sclerostin, osteoprotegerin, fibroblast growth factor 23 (FGF-23), parathyroid hormone, total calcium, phosphorus, alkaline phosphatase, creatinine, and urea. Follicle-stimulating hormone( FSH), luteinizing hormone(LH) and estradiol were determined by solid-phase chemiluminescent enzyme immunoassay (commercial sets of Alkor-Bio, St. Petersburg). Serum concentrations of sclerostin, sRANKL (soluble RANKL), and osteoprotegerin were determined by the enzyme-linked immunoassay using Biomedica gruppe test systems. Results The examined patients showed hormonal dysfunctions (82%), accompanied by changes in the content of sex hormones: the concentration of estradiol was below normal: 123.4±72.5 pmol/l and 150.0-450.0 pmol/l, respectively, in patients and in normal (p<0.01), which confirms the presence of estrogen deficiency in the examined patients . Concentrations of FSH and LH exceeded the norm in the group of patients as a whole: 91.6±46.1 IU/l and 3.0-8.0 IU/l FSH content in patients and normal; 51.8±32.1 IU/l and 3.0-10.0 IU/l LH in patients and normal. In the group of patients as a whole, an increase in the level of sclerostin to 28.5 ± 9.2 pmol/l was detected ( norm 12±33.45 pmol/l), an increase in the level of osteoprotegerin to 6.9±0.4 pmol/l (norm 2.7 pmol/l). Positive and negative correlations were found between the levels of morphogenetic proteins, sex hormones, and characteristic parameters of hormonal dysfunctions Conclusion Pre-and postmenopausal women with CKD have hormonal dysfunctions, including disorders of sexual and reproductive function, menstrual cycle, decreased fertility, increased risks of miscarriage at its onset, the basis of hormonal dysfunctions is the absence of LH peaks and changes in the concentration of estradiol depending on the phase of the cycle, hypoestrogenemia. It is assumed that there is a pathogenetic link between hormonal dysfunctions and disorders in the system of bone metabolism regulatory proteins in patients with CKD.
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