[Low protein diet with essential amino acids ketoanalogues combination can affect serum FGF-23 and Klotho levels in chronic kidney disease 3b-4 stages patients: randomized pilot study].

Protein restriction diet (PRD) with ketoanalagues of essential amino acids (KA) combination can improve of chronic kidney disease (CKD) course while, the precise mechanisms of PRD + KAA action in CKD are not known yet. We have conducted a prospective, randomized, controlled study of PRD and KAA patient's group in compare with PRD without KAA group in regarding to serum Klotho and FGF-23 levels in patients with CKD. MATERIALS AND METHODS: The study included 79 CKD 3b-4 stages patients, non - diabetic etiology, used PRD (0.6 g/kg/day). The patients were randomized in two groups: 42 patients, received PRD + KAA (Group 1) and 37 patients continued the PRD without KAA (Group 2). Serum FGF-23 (Human FGF-23 ELISA kit with antibodies to native FGF-23 molecule, Merk Millipore MILLENZFGF-23-32K), Klotho (Human soluble Klotho with antiKlotho monoclonal antibodies, IBL-Takara 27998-96Well) levels, as well as instrumental examination: bioimpedance analysis [assess of muscle body mass (MBM), fat body mass (FBM), body mass index (BMI) and others]; sphygmography [assess of augmentation (stiffness) indices (AI), central (aortal) blood pressure (CBP) by «Sphygmacor¼ device]; as well as echocardiography [assess of cardiac (valvular) calcification score (CCS) and left ventricular myocardium mass index (LVMMI)], were studded in addition to conventional examination. RESULTS AND DISCUSSION: To the end of 14th month of the study the PRD group reached a body mass index (BMI) decrease (p=0.046), including MBM in men (p=0.027) and woman (p=0.044). In addition, higher FGF-23 (p=0.029), and lower Klotho (p=0.037) serum levels were revealed in the PRD group compared to the PRD+KAA group as well as the increase in AI (p=0.034), CCS (p=0.048), and LVMMI (p=0.023). CONCLUSION: Use of PRD + KAA provides adequate nutrition status and more efficient correction of FGF-23 and Klotho imbalance in CKD progression that may contribute to alleviation of both cardiovascular calcification and cardiac remodeling in CKD. Importantly, a prolonged PRD use without supplementation of KAA may lead to malnutrition signs.

[Serum troponin-I as a marker of fibroblast growth factor-23 (FGF-23) cardiotoxic effect, in patients with chronic kidney disease].

AIM: It has been established that an increased fibroblast growth factor (FGF-23) serum levels significantly contribute to the heart and blood vessels remodeling in patients with chronic kidney disease (CKD). But the precise mechanisms of the FGF-23 cardiac effect are currently being actively studied. At the same time, it is believed that the cardiac effects of FGF-23 may be due to the increasing deficit of Klotho protein as CKD progresses. In parallel with these changes, a number of studies indicate the persistence of the detectable troponins serum levels in CKD patients, even in the absence of clear clinical manifestations of cardiovascular diseases (CVD). The aim of the study was to confirm / exclude the existence of a causal relationship between elevated FGF-23, reduced Klotho and elevated troponin-I (as the most specific troponin in CKD). MATERIALS AND METHODS: The study included 130 CKD stages 1-5D patients without clinically pronounced symptoms of СVD (Coronary artery disease, CCS class 2-4, Chronic heart failure, NYHA 24, myocarditis, pericarditis, arrhythmias), as well as the severe arterial hypertension (BP >160/90 mm Hg), according to the laboratory and instrumental methods of examination. The selected group of patients was studied: serum levels of FGF-23 (Human FGF-23 ELISA kit), Klotho (Human soluble Klotho with antiklotho monoclonal antibodies), troponin-I (high - sensitive assay), and also data from instrumental examination methods: electrocardiography (ECG), echocardiography (left ventricular myocardial mass index (LVMI), cardiac (valvular) calcification score (CCS) using a semi - quantitative point scale), sphygmagraphy (augmentation (stiffness) indices of vessels (AI), pulse wave velocity (PWV), central (aortic) blood pressure (CBP), blood supply of subendocardium (BSE) - using "Shygmacor" device (Australia)). RESULTS AND DISCUSSION: The changes in serum levels of FGF-23, Klotho and troponin-I (Tr-I) depended on the stage of CKD. The following correlations were identified: FGF-23 and: Tr-I (r=0.601; p.

ANESTHETIC MANAGEMENT AND INTENSIVE CARE DURING PERIOPERATIVE PERIOD OF ABDOMINAL DELIVERY IN PREGNANT WOMEN WITH PULMONARY ARTERIAL HYPERTENSION.

Background The presence ofpulmonary arterial hypertension (PAH) in pregnant women increases mortality up to 12- 30% and up to 50% when PAH is associated with Eisenmenger syndrome. Due to low prevalence of PAH in pregnancy many aspects ofperioperative management are still unclear. THE AIM: To summarize our approaches to the anesthesia and intensive care in pregnant women with PAH. MATERIALS AND METHODS: 21 pregnant women with PAH (systolic pulmonary artery pressure (SPAP) higher than 60 mm Hg)-who underwent delivery by Caesarean section in 2010 - 2015 were included in the one-centre retrospective study. Data are presented as median (25th, 75th percentile). RESULTS: The median age was 27 (23; 29) years. Among the patients, there were 4 (19%) cases of idiopathic PAH and in 17 (81%) women PAH was associated with congenital heart disease (CHD); 12 (57%) patients'demonstrated Eisenmenger syndrome. Baseline SPAP was 90 (82; 103) mm Hg. SpO2 90 (85,95)%. All women taken PAH-specific therapy (sildenafil) before delivery. Caesarean section (CS) were performed at 32 (28; 34) weeks. In 20 cases CS was perfofined under epidural anesthesia and in one case under general anesthesia due thrombocytopenia. Inhaled nitric oxide (NO) was administered intraoperative to all women in a dose of 40-60 ppm. Postoperative period was uncomplicated in five women (23?8%). Decompensation with PAP rise, acute right ventricular failure and hypoxemia developed in 16 (76,2%) cases 30 (24, 40) h after abdominal delivery. These patients required combined PAH-specific therapy (NO, sldenafil, iloprost) and inotropic agents, additionallyrespiratory support was used in four patients. The median ICU stay was 13 (9; 22) days. 3 patients died (14?2%); mortality in Eisenmenger syndrome cases was 25% (3/12). 18 healthy babies.

[General molecular and cellular mechanisms for renal and cardiac remodeling in chronic kidney disease: a target for nephrocardioprotection].

The lecture considers a number of molecular and cellular mechanisms underlying the structural and functional rearrangement and development of renal and cardiac fibrosis in chronic kidney disease (CKD). It details the key component of disadaptative organ remodeling (the formation of myofibroblasts via epithelial-mesenchymal and endothelial-mesenchymal transdifferentiation) and the role of leading angiofibrogenic mediators (angiotensin II, transforming growth factor-beta type 1, a plasminogen activator inhibitor type 1, etc.) in the regulation of these processes. Investigation of the molecular and cellular bases of organ fibrosis, including the factors of dysregulated activation, differentiation and survival of microfibroblasts, makes it possible to specify the mechanisms of action of traditional nephro- and cardioprotective agents, to offer a possibility for a goal-oriented (target) effect on individual fibrogenic components, and to expand the arsenal of medications suppressing renal and cardiac remodeling.

[Clinical implications of urine matrix metalloproteinases and their inhibitors in patients with chronic glomerulonephritis].

AIM: Estimation of urinary excretion of matrix metalloproteinases (MMP) and their inhibitors in patients with chronic glomerulonephritis (CGN), specification of the role of MMP and inhibitors as criteria of CGN activity and prognosis. MATERIAL AND METHODS: ELISA was used for measurement of urinary levels of basic proteolysis system components (MMP-2 and MMP-9), tissue inhibitor TIMP-2 and plasminogen activator inhibitor PAI-1 in four groups of patients. Patients of group 1 (n = 23) had CGN with manifest urinary syndrome (US), of group 2 (n = 26)--CGN with nephritic syndrome (NS), of group 3 (n = 22)--CGN with marked proteinuria (PU) and transient renal failure (RF), group 4 (n = 15)--CGN with high PU and persistent RF. RESULTS: Patients with enhancing CGN activity (marked US, developing NS, acute nephritic syndrome) had balanced elevation of urinary levels of MMP, TIMP and PAI-1. Development of persistent RF in CGN occurred with imbalance between components of proteolysis system--low urine excretion of MMP and elevation of PAI-1. Urine excretion of MMP and TIMP in patients with progressive CGN directly correlated with 24-h PU and negatively correlated with blood serum creatinine. PAI-1 correlated with severity of RF and fibrosis in renal tissue. CONCLUSION: Correlation of changes in urinary excretion of MMP, TIMP and PAI-1 with CGN activity, RF and fibrosis in the kidney confirm the importance of the above urinary tests for estimation of local renal proteolysis and validity of their use for monitoring of extracellulary matrix accumulation (fibrosis) in the kidney and for CGN prognosis.