[Fibroblast growth factor 23 and a novel high-sensitivity troponin I: Early markers and alternative ways of damaging the heart in chronic kidney disease].

AIM: To establish possible pathogenetic relationships between the marker of bone mineral metabolism fibroblast growth factor 23 (FGF-23) and the markers of cardiovascular diseases characterizing the state of cardiomyocytes and that of the vascular wall of the aorta and large vessels in chronic kidney disease (CKD). SUBJECTS AND METHODS: A total of 110 patients (57 men and 53 women) aged 25 to 65 years (mean age 56 ± 2.2 years) with different stages of CKD were examined. FGF-23 and troponin I in the sera from all the patients were investigated using enzyme immunoassay kits. Doppler echocardiography was carried out to evaluate the morphofunctional state of the left ventricle (LV). Peak systolic blood flow velocity in the aortic arch and common carotid intima-media thickness were estimated to assess the wall of the aorta and large arteries. RESULTS: As renal failure progressed, just at the early CKD stages the patients were found to have elevating FGF-23 and troponin I levels forestalling an increase in parathyroid hormone concentrations and changes in other calcium-phosphorus metabolism indicators. The levels of FGF-23 and the morphofunctional indicators of LV lesion showed a strong direct correlation that preserved its significance in analyzing the factors under study in relation to the function of the kidneys. CONCLUSION: The morphogenetic protein FGF-23 seems to play a significant role not only in bone remodeling processes, but also in the development of cardiovascular events in CKD. However, the mechanisms of its implication in the development of heart disease, like the possibilities of using its level changes as early diagnostic criteria for cardiovascular involvement, call for further investigation.

[Osteoprotegerin and fibroblast growth factor 23 in the development of cardiovascular events in chronic kidney disease].

AIM: To study the role of the bone mineral metabolic mediators osteoprotegerin (OPG) and fibroblast growth factor 23 (FGF-23) in the mechanisms of cardiovascular events (CVEs) in chronic kidney disease (CKD). SUBJECTS AND METHODS: Sixty-eight patients (30 men and 38 women) aged 38 to 64 years (mean age 49 +/- 6.3 years) with Stages III-VD CKD were examined. The stages of CKD were determined in accordance with the NKF-K/DOQI guidelines; glomerular filtration rate was calculated using the CKD-EPI formula. Serum OPG and FGF-23 were examined in all the patients, by applying commercial enzyme immunoassay kits. Doppler echocardiography was performed to evaluate the morphofunctional state of the left ventricle (LV). RESULTS: As renal failure progressed from Stage III to Stage VD CKD, the examined patients had higher serum OPG and FGF-23 concentrations. The levels of OPG and FGF-23 and the morphofunctional indicators of LV lesion, blood pressure, and anemia showed a strong direct correlation that preserved its significance in analyzing the factors in question in relation to the function of the kidneys and the pattern of cardiovascular system lesion. CONCLUSION: The morphogenetic proteins OPG and FGF-23 seem to play a significant role not only in bone remodeling processes, but also in the development of CVEs in CKD.

[The prevalence of anxiety and depression in different regions of the Russian Federation and its association with sociodemographic factors (according to the data of the ESSE-RF study)].

AIM: To study the prevalence of anxiety and depression by psychometric methods (the Hospital Anxiety and Depression Scale (HADS) in different regions of the Russian Federation (RF), which are characterized by various climatic, geographic, economic, and demographic indicators. SUBJECTS AND METHODS: The investigation used the data of the multicenter epidemiological survey of cardiovascular diseases in different regions of the Russian Federation--the ESSE-RF study. The subjects of the study were representative samples from unorganized male and female populations aged 25-64 years from 10 RF regions. The survey included a total 16,877 people (6244 men and 10,623 women). All the examinees were interviewed using a standard questionnaire. An analysis involved their gender, age, education level, place and region of residence, and income and morbidity level. The HADS validated in Russia was used to rate the level of anxiety/depression. RESULTS: The total prevalence of higher anxiety and depression averaged 46.3 and 25.6%, respectively. Respondents with clinical anxiety/depression constituted more than one third of those who had a higher level of these conditions. In the examined population, the moderate level of anxiety/depression was 7.5 ± 0.06 and 5.1 ± 0.04, respectively. The population of Volgograd, Samara, Saint Petersburg, and Tomsk had the similar values of the moderate level of anxiety/depression (p > 0.05). The lowest level of anxiety/ depression (p < 0.0001) was seen in the dwellers of Tyumen (5.9 ± 0.1 and 3.4 ± 0.1, respectively) and the highest in the Republic of North Ossetia-Alania (NOA) (8.4 ± 0.1 and 6.8 ± 0.1, respectively). These regions showed the lowest and highest prevalence of higher anxiety (22% in Tyumen and 59.8% in the Republic of NOA (p < 0.0001). CONCLUSION: All the 10 selected RF regions differing in demographic, economic, climatic, and geographical parameters are characterized by a high level of anxiety that remains statistically significant after adjusting for gender and age, so are parameters, such as income and morbidity levels are present in only 4 of the 10 regions.

[Diastolic dysfunction in different types of left ventricular hypertrophy in patients with end-stage renal failure: impact of long-term erythropoietin therapy].

AIM: To study the specific features of diastolic dysfunction (DD) in different types of left ventricular (LV) hypertrophy (LVH) in patients with end-stage renal failure (ESRF) and to estimate the cardioprotective effect of erythropoietin. SUBJECTS AND METHODS: 107 patients (57 women and 50 men) aged 22 to 63 years with ESRF were examined. The follow-up was 18 months. LV ejection fraction, peak early diastolic filling rate, peak late diastolic filling rate, their ratio, LV isovolumic relaxation time, LV end-diastolic diameter, LV end-diastolic volume, LV end-diastolic diameter index (EDDI), LV posterior wall and ventricular septal thickness, and LV mass index were determined. J. Gottdiener's classification based on the calculation of EDDI and LV relative wall thickness was used to estimate LV geometry. Erythropoietin was given to patients with the baseline level of hemoglobin (Hb) < 110 g/l or hematocrit (Ht) < 33%; and iron (III) hydroxide sucrose complex was used to those with ferritin < 100 microg/l or transferrin saturation < 20%. The target level of blood pressure was 130/80 mm Hg; Hb was less than 110 g/l for women and 120 g/l for men; Ht, > 33%. RESULTS: The patients with ESRF were found to have different types of DD and LVH, the severity of which correlated with the magnitude of renal anemia and arterial hypertension (AH). Adequate correction of anemia and AH promoted the transition of more to less severe DD and LVH and in a number of cases the recovery of LV structure and function. CONCLUSION: ESRF is characterized by different types of DD, which are pathogenetically closely related to different types of LVH. Adequate correction of renal anemia and AH may cause a significant reduction and, in a number of cases, alleviate VLH, and normalize LV systolic and diastolic functional values.

[Left ventricular hypertrophy in end-stage renal disease and its possible regression as a result of correction of anemia and arterial hypertension].

AIM: To ascertain mechanisms of development of left ventricular hypertrophy (LVH) and possible cardioprotective action of anemia correction in patients with end-stage renal disease. MATERIAL AND METHODS: A total of 98 patients (53 females and 45 males aged 49.4 +/- 14 years) on hemodialysis participated in the study. The patients were examined clinically with estimation of the levels of parathormone, calcium, phosphorus, erythrocytic indices, serum ferritin, blood transferrin. Echocardiography with dopplerography on Aloka-4000 unit were made. Left ventricular geometry was assessed by J. Gottdiener classification. Therapeutic policy aimed at correction of anemia, arterial hypertension, phosphorus-calcium metabolism. RESULTS: The patients were treated and followed up for 18 months. The examination was done before treatment, 12 and 18 months later. After the trial the patients were divided into 4 groups depending on the results obtained on LVH development. Blood pressure, hemoglobin, echocardiographic parameters changed according to the patient's group. After 18 months of observation and treatment with erythropoietin and iron preparations, ACE inhibitors, angiotensin II receptor blockers, beta-adrenoblockers, drugs regulating phosphorus-calcium metabolism some cases were seen of reduction of systolic blood pressure, achievement of target hemoglobin level, regression of LVH. CONCLUSION: Combined treatment of hemodialysis patients including antianemic, antihypertensive drugs promoted improvement of LVH or its regression in some cases.

[Role of free radical oxidation in the development of cardiovascular events in chronic renal failure].

AIM: to refine a role of free radical oxidation (FRO), anemia, and endothelial dysfunction in the development of cardiovascular events in patients with chronic renal failure (CRF) at diferent stages of the disease. SUBJECTS AND METHODS: Eighty-six patients, including 46 (53%) women and 40 (47%) men with Stages II-IV CRF, were examined. The patients' mean age was 43.6 +/- 14 years. Echocardiography, measurements of the blood levels of hemoglobin, albumin, cholesterol, and uric acid, and determination of blood electrolytic composition were made. Blood creatinine concentrations in the group averaged 0.3 mmol/l. Glomerular filtration rate (GFR) calculated from the Cockroft-Goult formula averaged 33.96 +/- 13 ml/min; the duration of CRF was 9.3 +/- 1.6 years. Anemia was detected in 46 (53%) patients. Iron metabolism was estimated from serum ferritin levels. Special studies involved determination of FRO--malondialdehyde (MDA) and the activities of catalase and superoxide dismutase (SOD) in plasma and serum. The plasma concentrations of endohelin-1 (ET-1), thromboxane A2, and prostacyclin were measured by radioimmunoassay. Results. The higher concentrations of MDA and the decreased activities of catalase and SOD, i.e., FRO, correlated with the progression of renal failure. There were also increases in the levels of ET-1 and thromboxane A, and a reduction in the concentration of prostacyclin as blood creatinine levels elevated. Left ventricular hypertrophy was found in 43 (50%) of the 86 patients. Its severity depended on the decrease of creatine phosphokinase and the severity of anemia and arterial hypertension. There was a stable correlation between the changes in left ventricular myocardial mass, MDA levels, and catalase and SOD activities. CONCLUSION: The higher level of MDA and the lower activities of catalase and SOD in patients with CRF, which correlate with diminished renal function, confirm that the disease is closely associated with FRO, that, by aggravating anemia and endothelial dysfunction, affects the magnitude of morphological and functional changes in the cardiovascular system in patients with CRF patients.

[The effect of magnesium pool isotopy on reactivation of mitochondrial ATP synthesis suppressed by 1-methyl-nicotine amide].

The ATP-generating activity of both rat myocardial mitochondria and intramitochondrial creatine phosphokinase (CPK) was examined as a function of the incubation medium magnesium pool isotopy. The in vitro systems tested were prepared from the hearts of animals treated with single injection of 1-methyl-nicotine amide (MNA) suppressing the NAD(P)-dependent reactions in vivo. The presense of the 25Mg paramagnetic cations leads to essential compensation of intramitochondrial ATP deficiency caused by the MNA induced blockade of oxidative phosphorylation. This effect is merely unreachable in those systems where the magnesium pool consists of isotopes with a zero nuclear spin (24Mg, 26Mg). The reactivation of mitochondrial ATP synthesis described here involves CPK activity which does not depends on MNA. In this case, a high efficiency of this reactivation seems to be a spin selective phenomenon which requires, predominantly, 25Mg2+ cations.

[Stable isotopes of Mg2+ as activators of the suppressed ATP-generating function of mitochondria].

The ATP-generating activity of rat myocardial mitochondria and intramitochondrial creatine kinase was examined as a function of the isotopy of the incubation medium magnesium pool. The study was performed using in vitro systems prepared from the hearts of animals injected with 1-methylnicotine amide, which suppresses the NAD (NADP)-dependent reactions in vivo. It was shown that the presence of the 25Mg paramagnetic cations essential by compensates for the intramitochondrial ATP deficiency caused by the 1-methyl-nicotine amide-induced blockade of oxidative phosphorylation. This effect is hardey achievable in systems where the magnesium pool consists of isotopes with a zero nuclear spin (24Mg, 26Mg). The restoration of mitochondrial ATP synthesis involves the participation of creatine kinase since the activity of the latter does not depend on 1-methyl-nicotine amide. In this case, the high efficiency of this restaration seems to be a spin-selective phenomenon which requires predominantly 25Mg2+ cations. A possible meaning of the data for further studies on the mechanisms of enzymatic catalysis regulation is discussed.

Matrix metalloproteinases of normal human tissues.

This review considers biochemical properties of the family of matrix metalloproteinases (MMPs) of normal human tissues and the involvement of these enzymes in morphogenesis. Four main MMP subfamilies are characterized, and a group of other MMPs is described. Data on mechanisms of activation and inhibition of MMPs in certain tissues during various physiological processes (embryogenesis, angiogenesis, tissue growth and involution) are considered. Information about tissue inhibitors of MMP is presented, and the ability of these inhibitors to regulate the activity of MMPs is analyzed.

Role of matrix metalloproteinases in development of diabetic nephropathy.

This review considers molecular mechanisms that underlie disorders in the structure and metabolism of renal extracellular matrix in diabetic nephropathy. The contribution of the increased synthesis of renal extracellular matrix proteins in the accumulation of renal mesangial matrix is considered, and the important role of the degradation system of the extracellular matrix proteins in the development of fibrosis is also shown. Data on changes in mRNA expression for the matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in various forms of diabetic nephropathy are presented. A correlation is established between changes in the balance of MMP proteolytic activity and TIMP activity and the accumulation of extracellular matrix.

[Functional state of the cardiovascular system in workers employed in lead production]. / Funktsional'noe sostoianie serdechno-sosudistoi sistemy u rabochikh, zaniatykh v proizvodstve svintsa.

The study covered health state of workers in lead workshop and revealed compromised heart functions, changes of intracardial and peripheral hemodynamics in most the examinees. Disorders of myocardial bioelectric activity and contractility, disturbed peripheral hemodynamics were more common in those occupational groups which are exposed to higher ambient lead amounts. Degree of the ailments appeared to correlate with length of service in lead workshop. Workers engaged into lead production proved decreased adaptational resources due to lower myocardial capacity.

[Characteristics of the serum lipids in workers of lead industry]. / Osobennosti lipidnogo sostava syvorotki krovi u rabochikh, zaniatykh v proizvodstve svintsa.

The study covered peculiarities of lipid metabolism in workers engaged into lead production. Most the examinees showed reliable increase of total blood cholesterol, low and extremely low density lipoproteins cholesterol, triglycerides and atherogenic coefficient, combined with decreased high density lipoproteins cholesterol. Occupational factor was proved dominant in atherosclerosis formation in lead production workers. Those workers demonstrated also significant comedown of Apo A-1 amount, reliable increase of Apo B level and Apo B/Apo A-1 ratio.