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Title: [MORPHOGENETIC PROTEINS--FIBROBLAST GROWTH FACTOR AND KLOTHO, IN THE SERA OF PATIENTS WITH CHRONIC RENAL DISEASE].
Author: Milovanova LY, Kozlovskaya LV, Markina MM, Milovanova SY, Borisov AA, Mukhin NA, Fomin VV, Moiseev SV.
Journal: Klin Med (Mosk); 2015; 93(12):32-8. PubMed ID: 27149811.
Abstract:
The aim of the study was to evaluate the role of morphogenetic proteins--fibroblast growth factor-23 (FGF-23) and extracellular form (alpha) of Klotho protein, present in the sera of patients with chronic renal disease (CRD) as markers of cardiovascular risk. The study included 130 patients (64 men and 66 women) with stage I-VD CRD. The patients'age was 20-65 (mean 41 ± 6.7) years. 30 of them had chronic glomerulonephritis, 23 chronic tubulointerstitial nephritis, 28 hypertensive nephrosclerosis, 22 polycystic kidneys, 27 type 2 diabetes mellitus. Inclusion and exclusion criteria were standardfor clinical studies of CRD patients. Control group contained 30 healthy volunteers matched for age and sex. The patients were uniformly distributed by stages of CRD in terms of age and sex (18-20 per group). All of them were followed up during 1 year Standard clinical and laboratory examination was supplemented by the measurement of the parathyroid hormone (PTH), Ca and P levels. Serum FGF-23 and Klotho levels were determined by ELISA before and 1 year after onset of the study. Blood pressure including brachial (peripheral) and aortic (central) one as swell as the pulse wave velocity was measured by a Sphygocorr apparatus (Australia). Other studies included ECG, EchoCG, and X-ray of abdominal aorta in the lateral projection using the Kaupilla method. Comparison of FGF-23 and Klotho levels in patients at different stages of CRD revealed their decrease with decreasing glomerular filtration rate that started before (at IIIA stage) a rise in the serum P and PTG levels (IV-V stage). Negative relationship was documented between the Klotho level and the degree of cardiac calcinosis estimated from a semi-quantitative scale (r = 0.64; p < 0.01). Serum FGF-23 significantly correlated wiht myocardial remodeling (r = 0.612; p < 0.01). Multiple regression analysis showed that patients with elevated FGF-23 and P levels, high central systolic pressure and pulse wave velocity had greater left ventricular myocardium mass. ROC-analysis demonstrated that FGF-23 level over 412 pg/ml is indicative of left ventricular hypertrophy with sensitivity 80% and specificity 76%. Patients undergoing hemodialysis who died within 1 year after the onset of the treatment had a higher FGF-23 level than survivals on hemodialysis. The risk of death during the first year on hemodialysis correlated with the FGF-23 level (r = 0.564, p < 0.01). ROC-analysis showed that Klotho levels below 387 pg/ml suggested an increased risk of myocardiym calcification with sensitivity 80% and specificity 75%. It is concluded that morphogenetic proteins, fibroblast growth factor and Klotho, not only play an important role in mineral metabolism in patients with CRD but also produce pleiotropic effects on the development of cardiovascular complications (via involvement in cardiac and vascular calcification and remodeling). It provides a basis for the use of these proteins as early markers of cardiovascular risk in CRD patients.

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