Since it was discovered, the citric acid cycle has been known to be central to cell metabolism and energy homeostasis. Mainly found in the mitochondrial matrix, some of the intermediates of the Krebs cycle are also present in the blood stream. Currently, there are several reports that indicate functional roles for Krebs intermediates out of its cycle. Succinate, for instance, acts as an extracellular ligand by binding to a G-protein coupled receptor, known as GPR91, expressed in kidney, liver, heart, retinal cells and possibly many other tissues. Succinate activated GPR91 induces a wide array of physiological and pathological effects. Through GPR91, succinate is involved in functions such as regulation of blood pressure, inhibition of lipolysis in white adipose tissue, development of retinal vascularization, cardiac hypertrophy and activation of stellate hepatic cells by ischemic hepatocytes. Current review is dedicated to discussion of these effects. 

Succinate is hypoxic stress signal metabolite. Entering the patient’s body from the dialysate during hemodialysis, succinate inhibits prolylhydroxylases, leading to stabilization of hypoxia-inducible factor (HIF) and to the deployment of many HIF-mediated effects. Application of succinate-containing dialysis solutions can be considered as pseudohypoxic preconditioning, which provides the beneficial effect on several clinical and biochemical parameters of patients. 

THE AIM. To assess hypercoagulation factors in men with initial decrease of glomerular filtration rate (IDGFR) and metabolic syndrome (MS) depending on carbohydrate metabolism disorders (CMD). PATIENTS AND METHODS. The study included 79 men with IDGFR and MS. Two groups were assessed: main – patients IDGFR and CMD with MS (n=44) and control group – with IDGFR and MS without CMD (n=35). Besides examinations for confirming IDGFR and CMD type specification all patients were performed following tests: estimated thrombodynamics factors, serum concentration of common testosterone (CT), leptin (L), adiponectin (A), D-dimer (DD), activated platelets count (CD41+CD62P+) (APC), PAI-1, homocysteine (H). We also studied polymorphism of the genes associated with hyperhomocysteinemia (HHC). RESULTS. 90% cases of hyperhomocysteinemia (HHC) in men with IDGFR and MS were associated with genetic defects in enzyme systems regulating this amino acid metabolism.. Patients from the main group in comparison with the subjects without CMD had significantly higher density of the fibrin clot  (28012,21±1013,60 vs. 25209,15±1176,90 c.u., р<0,05), serum levels of PAI-1 (78,78±13,00 vs. 43,66±4,00 ng/ml, p<0,01), leptin (13,56±1,40 vs. 8,95±1,60 ng/ml, p<0,01) and lower serum concentration of CT (11,54±0,70 vs. 14,50±1,10 nmol/l, p<0,05). In men with IDGFR and MS with CMD we found positive correlations between activated platelets count and fasting glucose (rs=0,4; р<0,05), activated platelets count and postprandial glucose (rs=0,5; р<0,05), PAI-1 and adiponectin (rs=0,4;  р<0,05), PAI-1 and leptin (rs=0,4; р<0,05), homocysteine and MCH (rs=0,5; р<0,05), homocysteine and density of the fibrin clot (rs=0,5; р<0,05), insulin and PAI-1 (rs=0,4; р<0,05), adiponectin and density of the fibrin clot (rs=0,4; р<0,05), hemoglobin and clot growth rate (rs=0,4; р<0,05), RDW and D-dimer (rs=0,4; р<0,05), RDW and density of the fibrin clot (rs=0,6;  р<0,05); a negative correlation – between fasting glucose and adiponectin (rs= -0,4; р<0,05). CONCLUSION. CMD in men with IDGFR and MS are associated with procoagulant status via direct and indirect influence on hypercoaculation factors. The role  of adiponectin in thrombogenesis is controversial and requires further investigations. 

AIM: research of multimorbidity as a risk factor for contrast induced nephropathy after X-ray endovascular intervention in patients of senior age groups. PATIENTS AND METHODS. Patients of following age groups were examined: 34 – 59 years (49,7±7,8 years) – 35 people (control group), 60 – 74 years (66,1±4,1) – 48 people and 75 – 82 years (78,8±4,2) – 22 people. Kidneys functional status examination was performed in patients of advanced and senile age before and after 24, 48 120 hours after X-ray endovascular intervention. Effect of multimorbidity states on contrast induced nephropathy (CIN) development. RESULTS. Strong correlation between different multimorbidity factors, serum creatinine concentration in different time periods after X-ray endovascular intervention and risk of CIN was revealed. CONCLUSION: in patients of advanced and senile age multimorbidity is a risk factor for CIN development when carrying out X-ray endovascular interventions. 

THE AIM. Assessment of the impact of renal dysfunction and imbalance of body aquatic environments distribution on the risk of developing cardiovascular complications in the late period after acute coronary syndrome (ACS) and myocardial revascularization. PATIENTS AND METHODS. We examined 120 patients with ACS undergoing myocardial revascularization. We estimated traditonal and renal risk factors (albuminuria 30-300 mg/l, the value of GFR, acute kidney injury development), and body aquatic environments factors. Upon completion of the primary material processing, to determine the effect of the studied risk factors, we selected combined endpoint of the study – development of arrhythmias or death of patients, which were registered 6 months after restoration of coronary blood flow. RESULTS. By results of the carried out research we established effect on the probability of cardiovascular complications (CVC) by such risk factors as the presence of albuminuria, and acute kidney injury (AKI). AKI episode in patients with ACS associated with increase of arrhythmias and death possibilities in late period. It is established that AKI coupled with an imbalance of body aquatic environments increases the CVC development possibility 6 months after percutaneous coronary intervention in patients with ACS. CONCLUSION. In patients with ACS and myocardial revascularization revealed prognostic impact of the AKI and failure of body aquatic environments at the risk of CVC. 

THE AIM: to estimate the level of expression miRNA-21 inthe urine and renal tissue in rats with unilateral ureteral obstruction (UUO). MATHERIAL AND METHODS. UUO was induced by ligation of the left ureter in male Wistar rats (n=10). Follow-up period was 14 days after UUO modeling. Urine was collected one day before the operation (UmiRNA21_C), and one day before the end of experiment (UmiRNA21I ) during 24 hours. Before releasing animal out of experiment collected urine from left kidney pelvis (UmiRNA21O) and tissue of left kidney (KmiRNA21_O) and right kidney (KmiRNA21_I ). MiRNA-21 expression in kidney tissues and urine was carried out with reaction amplification (RealTime PCR-protocol). Calculation was realized by 2-^deltaCt method. Statistical analysis was performed with Wilcoxon test and Spearman correlation coefficient. Results are demonstrated as median [low – upper quartile]. RESULTS. UmiRNA21_I (3.78[2.0-5.28]) and UmiRNA21_O (3.78[3.25-3.82]) were significantly higher than UmiRNA21C (1.15[0.71-1.74]; P=0.0125 and P=0.0069, respectively). UmiRNA21I and UmiRNA21O values were practically equal. In kidneys with UUO the tissue levels of miRNA21 expression was a higher than in contralateral organ (P=0,0926). Revealed direct correlation between KmiRNA_I and KmiRNA_O (RS=0,770, P=0,0092). CONCLUSION. UOO can cause specific changes in the expression, distribution and excretion of micro RNA-21 and its role in the development of renal tubulointestitsial fibrosis requires further studies. Key words: miRNA-21, tubulointerstitial fibrosis, unilateral ureteral obstruction

THE AIM. To assess the effectiveness of selective agonist of PPAR gamma receptors (Peroxisome Proliferator-Activated Receptor) pioglitazone, as a drug of prevention and treatment of experimental urate nephropathy. MATERIAL AND METHODS. The study was conducted on 37 male rats Wistar stock. For the formation of urate nephropathy in rats inhibited uricase by co-administration of uric acid and oxonium. For the prevention and treatment of experimental pathology animals received pioglitazone. On day 21 using biochemical and morphological techniques were evaluated received changes. RESULTS. In the experimental condition were observed significant decrease of urate stones in kidneys, significant decrease of uric acid in blood plasma and urine of rats, increase of the urine pH, increase of glomerular filtration rate and inhibition processes of free radical oxidation in the blood of animals. CONCLUSION. Long-term use of pioglitazone in the preventive and therapeutic modes, significantly improves the experimental urate nephrolithiasis. 

THE AIM: to study of the dynamics of structural changes in renal parenchyma of rats exposed to long-term combined effects of thyroxine and propylthiouracilum (PTU). MATHERIAL AND METHODS – studies were performed on mongrel white male rats weighing 250-300g. Hyperthyroidism was caused by daily intragastric administration of thyroxine (T4) in amount of 50g per 100g of body weight over 30 days. On the first day of the experiment animals were divided into 2 groups. Animals of the first group (n = 25) received only T4. The rats of the second group (n = 25) were administrated propylthiouracilum and T4 daily. PTU was administered intragastric in amount of 1 mg per 100g of body weight. Kidney tissue samples were collected on the 10th, 20th and 30th days of the experiment. In addition, there were collected kidney tissue samples of the animals treated with only T4 after 20 days after cessation of hormone. Obtained tissue samples were fixed and treated by the usual method, followed by filling in paraffin. Sections were stained with hematoxylin and eosin. RESULTS – it was established that course of experimental hyperthyroidism leads to significant structural abnormalities of the renal parenchyma. Leading features of kidneys pathology at a hyperthyroidism are rough structural damages of the nephron tubular epithelium. CONCLUSIONS – combined administration in rats of thyroxin and propylthiouracilum has weakly expressed beneficial effect by limiting the development of structural damages to the renal parenchyma and clot formation. 

THE AIM: to determine reference limits of volume, osmolality and concentration of Na⁺, K⁺, Cl⁻, non-organic phosphate (P_i ), and Ca²⁺ in amniotic fluid (AF) of rabbits on 27-28 day of gestation. MATERIALS AND METHODS: during research on first-pregnant rabbits (n=6), received 37 samples of AF, determined fetal mass, fetal part of placenta mass, volume, osmolality and concentration of Na⁺, K⁺, Cl⁻, Pi , and Ca²⁺. RESULTS: obtained reference limits of volume (0,09–1,63 ml), osmolality (210,0–267,0, mOsmol/kg), concentration of ions Na⁺ (110,0–146,0 mmol/l), K⁺ (6,0–12,4 mmol/l), Cl^– (87,0–117,0 mmol/l), Ca²⁺ (1,88– 2,89 mmol/l) and P_i (0,56–1,57 mmol/l) in AF. Reverse correlation of AF volume with fetus mass (r = -0,525, p < 0,001) and positive correlation between fetus mass and AF osmolality (r = 0,375, p = 0,022) were determined. Concentrations of Na⁺, K⁺, Cl⁻ are correlated with placenta mass (r = 0,368, p = 0,025; r = 0,353, p = 0,032; r = 0,381, p = 0,020, respectively). AF osmolality correlated with concentrations of Na⁺ (r = 0,514, p < 0,001) and Cl(r = 0,510, p < 0,001). CONCLUSION: results could be used for developing animal models of medicamental influence on AF volume, osmolality and ion composition on late gestation. 

AIM: to analyze functional state of kidneys in women with urinary incontinence. PATIENTS AND METHODS: 277 women with complaints on urinary incontinence and 14 healthy women aged 18 to 55 years were examined. 143 women was diagnosed stress urinary incontinence, 43 – urge urinary incontinence and 91 – mixed urine incontinence. Nycturia was revealed in 24 women and polyuria – in 60 women with urine incontinence. The increased diuresis, water reabsorption in collecting ducts, ion excretion including Na and Mg ion were higher during the night in patients with nycturia and during the day in patients with polyuria in comparison with healthy patients. Use of desmopressin (minirin) in a dose of 100 mcg reduced diuresis and ion excretion to normal levels. It is suggested that the main role in the pathogenesis of kidney functions in patients with polyuria and nycturia is played by a decrease of ion reabsorption in the thick ascending Henle loop, which results in higher load of collecting ducts by liquid, increase of diuresis and electrolytes excretion. Use of desmopressin in these patients is pathogenetically proved because it removes main tubular defect. 

Improved knowledge of molecular mechanisms of the damaging effect of thermal ischemia and reperfusion to renal tissue of patients with renal cancer has significant prospects for new therapeutic approaches aimed at enhancing quality of care. THE AIM: to study changes in the expression of apoptosis-regulating genes MDM 2, BAX, CASP7, CASP3, CASP8, CASP9, BCL2, CASP8 / FADD, p53, APAF1, AIFM1, ICAD and XIAP in renal tissue of patients with renal cell carcinoma subjected to the action of ischemia and reperfusion. PATIENTS AND METHODS. We used for the study tissue biopsies of 12 patients with histologically confirmed diagnosis of renal cancer. Needle biopsy was performed before stop the blood supply, for 10 minutes of ischemia and 20 minutes after reperfusion in the kidney. The relative expression of genetic loci was determined by real-time PCR. RESULTS. It was found: 1) absence from the 10th minute of ischemia significant differences transcriptome profile of the majority of investigated genes from similar parameters prior to ischemia, with the exception of reducing expression of genes CASP7 and ICAD; 2) a significant increase in expression of pro-apoptotic genes (BAX, CASP3/7, APAF1 and p53), and anti-apoptotic genes (XIAP, MDM2 and BCL2) 20 minutes after reperfusion of the kidney tissue; 3) a changes in the balance of expression of pairs of proand anti-apoptotic genes p53 / MDM2 and Bax / BCL2 in the 10th minute of ischemia and 20 minutes after reperfusion. CONCLUSION. These data characterize transcriptomic state of renal tissue in the early period after ischemia and restore the blood flow in it as the initiation point shift the balance of proand anti-apoptotic genes. 

THE AIM: To study the state of the proand antioxidant system at the systemic and local level in acute serous and purulent pyelonephritis (ASP, APP). PATIENTS AND METHODS. Oxidative status was studied in 62 patients with ASP and APP, randomized by age, sex, the minimum number of co-morbidities in remission. RESULTS. It was found that the ASP, to a greater extent with the APP on the system (blood plasma, red blood cells) and local level (urine) increases the concentration of stable metabolites of nitric oxide, increases the content of lipid peroxidation products (alkyl hydroperoxides, malonic dialdehyde) and decreases the activity of the antioxidant system (superoxide dismutase levels, catalase, in plasma, urine and erythrocytes). After the comprehensive treatment of the studied indices at ASP are corrected or normalized, and at APP are subject to a minimum correction. CONCLUSION. The results reveal changes of oxidative status occurring in acute serous and purulent pyelonephritis, and also confirm the need for the comprehensive treatment of this disease using drugs with antioxidant and cytoprotective effects. 

Recently has greatly improved diagnosis of hereditary thrombophilia. Unlike other forms of methylene tetrahydro folate reduktase gene mutation (MTHFR) that are characteristic of both venous and arterial thrombosis. In the literature described isolated cases of thrombosis of renal vessels in adults. The authors describe their own observation of a child with a congenital heart defect, who inherited thrombophilia manifested by the development of left-sided occlusion of the renal artery, resulting in severe renovascular hypertension and nephrosclerosis of left kidney. The girl on molecular genetic testing revealed a homozygous carrier of the plasminogen I type inhibitor allele, compound heterozygous allele carriers of MTHFR, heterozygous carrier of the methionine synthase reductase (MTRR) allele.

The article is devoted to the outstanding scientist anatomist, paleontologist, doctor of biological sciences, lieutenant-colonel of medical service A. P. Bystrov (1899–1959), who lived only 60 years. Twenty-five years he was connected with the military department, two years worked inMoscowin the Paleontological Institute, the last 13 years of his life he taught at the geological faculty ofLeningradstate university.