[Clinical significance of uremic toxin indoxyl sulfate and inflammation in the development of vascular calcification and cardiovascular complications in stage C3-C5D chronic kidney disease].

AIM: To clarify the role of the uremic toxin indoxyl sulfate (IS) and inflammation in the development of vascular calcification and cardiovascular complications in chronic kidney disease (CKD). MATERIALS AND METHODS: One hundred fifteen patients aged 25 to 68 years with CKD stage C3-C5D were examined. Serum concentrations of IS, interleukin 6 (IL-6), tumor necrosis factor (TNF-α), troponin I, parathyroid hormone were determined by enzyme immunoassay using kits from BluGene biotech (Shanghai, China), Cloud-Clone Corp. (USA), ELISA Kit (Biomedica, Austria). RESULTS: An increase in the serum concentration of IS, IL-6, TNF-α was revealed, which was significantly associated with a deterioration in renal function and changes in the morphological and functional parameters of the heart and aorta. CONCLUSION: High concentrations of IS, IL-6, TNF-α, which are closely associated with an increase in renal failure and cardiovascular complications, indicate their significant role in vascular calcification, which underlies the damage to the cardiovascular system in CKD.

[Clinical significance of serum levels of osteoproteherin and sclerostin in assessment of vascular calcification in chronic kidney disease stage 3-5].

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.

[Role of fibroblast growth factor 23 in the development of cardiovascular diseases in patients with end-stage renal failure on programmed hemodialysis]. / Rol' 23-go faktora rosta fibroblastov v razvitii zabolevanii serdechno-sosudistoi sistemy u bol'nykh s terminal'noi stadiei pochechnoi nedostatochnosti, nakhodyashchikhsya na programmnom gemodialize.

AIM: To determine the nature of changes in fibroblast growth factor 23 (FGF-23) and other bone mineral metabolism parameters detectable in the blood of patients with end-stage chronic renal failure (CRF) and to analyze their links to the development of cardiovascular events in uremic intoxication. SUBJECTS AND METHODS: A total of 75 patients (45 men and 30 women) aged 23 to 66 years (mean age, 53±2.1 years) with Stage VD CKF were examined. The levels of parathyroid hormone (PTH), calcium, phosphorus, the morphogenetic protein FGF-23, and the cardiospecific protein troponin I were investigated. Doppler echocardiography was performed on an Aloka 4000 machine. Left ventricular (LV) mass index (LVMI), LV systolic and diastolic function, and peak systolic blood flow velocity in the aortic arch (Vps) were estimated. RESULTS: As LVMI became higher, there were increases in the level of PTH and that of FGF-23 that plays a significant role in the processes of bone remodeling and vascular calcification. Analysis of correlations between a change in FGF-23 concentrations depending on the morphological and functional parameters of the cardiovascular system (CVS) revealed a strong direct correlation between FGF-23 levels and LVMI (r=0.746; p<0.01), a significant inverse correlation between FGF-23 and ejection fraction (r=-0.901; p<0.05), and a direct correlation of FGF-23 and troponin I (r=0.544; p<0.05). CONCLUSION: FGF-2 increasing from moderate to very high levels indicates that there is a high risk for remodeling processes in the CVS even in the absence of baseline echocardiographic signs of myocardial hypertrophy, normal aortic pulse wave velocity, and compensation of other risk factors, such as hypertension, uremia, hyperparathyroidism, even without increasing the markers of cardiovascular events, such as hyperphosphatemia. The elevated level of FGF-23 suggests that there is a need for cardioprotective therapy, the goal of which is to correct of the level of this factor.

[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.

[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.

[Endothelial dysfunction in severe forms of acute renal failure. New approaches to pathogenetic therapy].

AIM: To study endothelial function in different variants of acute renal failure (ARF) at various stages of the disease. MATERIAL AND METHODS: The study of 36 patients with severe ARF at the stages of oliguria and recovery of diuresis included a clinico-laboratory analysis of characteristics of ARF of various etiology and follow-up of plasmic concentrations of endothelin-1, thromboxan A2 and prostacyclin in different ARF variants at different ARF stages. RESULTS: The oliguric phase of severe ARF ran with significant elevation of the level of vasoconstrictive endothelial hormones (endothelin-1 and thromboxan A2 and a fall of a vasodilator prostacyclin. Recovery of diuresis normalized the above parameters. CONCLUSION: Mechanisms of ARF development involve endothelial dysfunction manifesting with alteration of vasoactive hormones synthesis with a dominant rise of a vasoconstrictive hormones concentration.

[Thromboxane A2 and prostacyclin in patients with chronic glomerulonephritis and coronary heart disease in contrast media nephrotoxicity. Protective effects of calcium antagonists]. / Tromboksan A2 i prostatsiklin u bol'nykh khronicheskim glomerulonefritom i ishemicheskoi bolezn'iu serdtsa v usloviiakh nefrotoksicheskogo deistviia rentgenokontrastnykh sredstv. Protektivnoe deistvie antagonistov kal'tsiia.

AIM: To study pathological significance of circulating thromboxane A2 and prostacyclin in mechanisms of impairment of intrarenal hemodynamics and renal function due to contrast media (CM) in risk group patients and to study protective effects of calcium antagonists in CM nephrotoxicity. MATERIALS AND METHODS: To study plasmic concentrations of TxA2 and prostacyclin, we used radioimmunoassay to measure plasmic TxB2 and 6-keto-prostaglandin F1a in patients with chronic glomerulonephritis (group 1), systemic atherosclerosis and coronary heart disease (group 2). The control group consisted of 23 healthy subjects. Diatrizoate (verografin), a high-osmolar CM, was used (40-60 and 250-400 cc in groups 1 and 2, respectively). RESULTS: Plasma TxB2 and serum creatinine concentrations were significantly elevated in group 1 after CM infusion compared to the preinfusion period and healthy controls. Plasma 6-keto-prostaglandin F1a in group 1 before CM infusion was lower than in controls after CM infusion. The data in group 2 were similar to those for group 1. Administration of nifedipine before and after introduction of CM prevented a rise in serum creatinine and had beneficial effects on TxA2 and prostacyclin synthesis. CONCLUSION: Ionic CM have a renal vasoconstrictive effects mediated by imbalance between vasoconstrictor TxA2 and vasodilator prostacyclin and may be nephrotoxic in risk group patients. The protective effects of calcium antagonists promote normalization of calcium dependent TxA22 and prostacyclin synthesis.

[Endothelin-1 in the mechanisms of the nephrotoxic action of x-ray contrast media]. / Endotelin-1 v mekhanizmakh nefrotoksicheskogo deistviia rentgenokontrastnykh sredstv.

The authors study mechanisms of nephrotoxic action of high-osmolar radiopaque substance (RPS) and the role of endothelin-1, hormonal endothelial factor, in these mechanisms in patients with different variants of chronic glomerulonephritis. Endothelin-1 is a potent endogenic vasoconstrictor participating in regulation of intrarenal hemodynamics and renal function the synthesis of which id related to Ca metabolism. Mechanisms of nephrotoxic action of RPS involve disturbances of Ca metabolism (hypercalcemia), high concentration of blood endothelin-1 which directly correlated with baseline creatinine in the serum and deterioration of renal function after RPS introduction. Ca ions antagonists (corinfar) contribute to prevention of changes in endothelin-1 synthesis relevant renal dysfunction induced by RPS.

[New approaches to the pathogenetic therapy and prevention of acute kidney failure related to the use of x-ray contrast agents]. / Novye podkhody k patogeneticheskoi terapii i profilaktike ostroi pochechnoi nedostatochnosti, sviazannoi s primeneniem rentgenokontrastnykh sredstv.

The authors analyze causes, mechanisms underlying acute renal failure (ARF) attributed to tests with application of radioopaque substances and results of ARF treatment in 12 ARF patients and on Wistar rats models. It is inferred that ARF is a frequent and severe complication of the above tests which may be treated successfully by early application of dialysis, filtration, sorption, plasmapheresis techniques. Disorders of calcium metabolism and their correction contribute to ARF onset. Radio-opaque substances have essential inhibiting action on nitrogen oxide synthesis in the kidneys of experimental animals.

[Acute kidney failure from the nephrotoxic action of x-ray contrast media]. / Ostraia pochechnaia nedostatochnost' pri nefrotoksicheskom deistvii rentgenokontrastnykh sredstv.

Causes and mechanisms involved in the onset of severe forms of acute renal insufficiency induced by highly osmotic ionic x-ray contrast media have been analyzed for 9 patients suffering from renal and other diseases. Risk factors and factors of principal importance in promotion of nephrotoxicity of contrast media are the following: preexisting renal dysfunction, cardiovascular insufficiency, hypovolemia, calcium and sodium dysbolism. Approaches to prevention of contrast media nephrotoxicity with employment of forced diuresis, vasodilators, calcium channels blockers are under consideration.

[The preliminary results of a study of the role of endogenous nitric oxide in pregnant women with chronic glomerulonephritis, hypertension and puerperal eclampsia]. / Predvaritel'nye rezul'taty izucheniia roli éndogennogo oksida azota u beremennykh s khronicheskim glomerulonefritom, gipertonicheskoi bolezn'iu, rodovoi éklampsiei.

NO-synthase activity and formation of ERP/NO were evaluated in 19 pregnant women by high activity of platelet guanylate-cyclase (GC) and presence of z-arginine. The examinees were divided into 4 groups: 3 women with chronic glomerulonephritis (CGN), 9 patients with essential hypertension (EH), 3 nonpregnant women of reproductive age with EH, 3 healthy pregnant women. One patient had puerperal eclampsia. Z-arginine activation failed to change GC activity in healthy pregnant women, reduced it in pregnant and nonpregnant women with EH, increased GC activity 1.6-fold in a patient with puerperal eclampsia and in CGN pregnant females. It is inferred that changes in NO-dependent synthesis of cGMP manifested more distinctly in a patient with puerperal eclampsia.

[Tubular interstitial disorders in the nephrotoxic action of antibiotics]. / Tubulointerstitsial'nye narusheniia pri nefrotoksicheskom deistvii antibiotikov.

Experimental and clinical evaluation of antibiotic nephrotoxicity suggest a conclusion that these drugs may cause tubular damage in relatively unaffected function of tubular apparatus. Progression of tubular dysfunction results from accumulation of high concentrations of antibiotics in renal parenchyma due to tubular filtration and secretion of the drug by tubular epithelium cells. In the majority of patients the disease manifestations were directly associated with antibiotics administration. Tubular dysfunctions present as concentration, acid-excretion, glucose transport and beta 2-microglobulin reabsorption abnormalities. Though renal lesions proved benign, there were occasional cases of acute renal insufficiency in the absence of arterial hypertension.

[Acute kidney failure related to the use of x-ray contrast agents and indomethacin: the risk factors and mechanisms of its development]. / Ostraia pochechnaia nedostatochnost', sviazannaia s primeneniem rentgenokontrastnykh sredstv i indometatsina: faktory riska i mekhanizmy razvitiia.

7 acute renal failure (ARF) and experiments provided information on ARF induced by radio-opaque substances and indomethacin. The leading mechanism underlying renal failure is supposed to be the spasm of renal afferent arterioles secondary to hypercalcemia, prostaglandin synthesis blockade, activation of renin-angiotensin system and high activity of adenosine.