Recent studies have clearly linked higher serum inorganic phosphate (Pi) concentrations and an imbalance of Pi-regulating kidney-bone-parathyroid endocrine and paracrine systems to cardiovascular disease (CVD) events and mortality. This association has been identified in patients with chronic kidney disease (CKD) and in the general population. This editorial discusses the available clinical and experimental data in frames of the conception linking pathophysiology of phosphate exchange disorders related to CKD and CVD events.

During pharmacoeconomic analysis researches can use various pharmacoeconomic methods. These ones depend on aim and purposes of research. At the same time modern choice of pharmaeconomic analysis methods doesn’t mean uniform approach to estimation of various diseases. Specific features of both investigated objects and every particular group of diseases reflect during pharmacoeconomic evaluation. This article covers general moments of pharmacoeconomic analysis procedure and also presents features of such analysis in chronic kidney disease estimation. The aspects of effectiveness criteria choice for pharmacoeconomic analysis used in the “cost-effectiveness analysis” and “budget impact analysis” have been described. It has been shown that the specificity of the analyzed disease is reflected at all stages of pharmacoeconomic studies: elaboration of study design, choice of efficacy endpoint, determination of the research costs profile, implementation of particular methods of pharmacoeconomic analysis, interpretation of the results of pharmacoeconomic evaluation. It was found that pharmacoeconomic analysis of renal replacement therapy in patients with chronic kidney disease is the most specific.

The review presents data on the molecular mechanisms underlying podocytes and mesangial cells damage in glomerular hypertension. Mechanical stress in these cells activates the local RAS and increases the secretion of Ang II which in autocrine and paracrine manner stimulates AT1-receptors and triggers signaling cascades, leading eventually to the EMT-like phenotype changes, apoptosis podocytes and mesangial cells profibrotic degeneration. A key role in these processes plays a TGF-ß, which activates signaling pathways that mediate the majority of the pathological effects occuring in these cells upon mechanical damage and excitement of AT1-receptors of their cell membranes. At low concentrations TGF-ß induces in podocytes Smad 2/3-dependent and other intracellular signaling cascades which induce EMT-like changes and dedifferentiation of cells and at high concentrations together with Ang II activates signal pathways leading to apoptosis and loss of podocytes in glomerular filter structure. In glomerular mesangial cells TGF-ß and Ang II trigger signaling pathways which cause excessive accumulation of mesangial matrix and stimulate the production of MCP-1, TNFα, IL-18 and IL-6 inducing the inflammation of mesangial tissue. Elucidation of the molecular mechanisms of podocytes and mesangial cells damage in glomerular hypertension provides to identify potential targets for creation a new drugs development for the treatment of hypertensive patients with nephropathy of different origin.

This article provides native and foreign literature review about effectiveness of testis biopsy and assisted reproductive technologies (ART) in men with azoospermia caused by microdeletion of Y-chromosome long arm AZF locus and Klinefelter’s syndrome.

THE AIM: phase III multicenter open-label randomized comparative trial on efficacy and safety of calcium polystyrene sulfonate for correction of hyperkalemia in patients with renal failure not requiring dialysis compared with low potassium diet was performed for evaluation of efficacy and safety in 5 investigational sites of Russia. PATIENTS AND METHODS: the study included patients with level of potassium in the plasma 5.5 -6.5 mmol/L. Patients received calcium polystyrene sulfonate 30 g per day during 5 days and kept a low potassium diet. Control group was treated with only low potassium diet. Primary end-point was reduction in serum potassium concentration by Day 5 of treatment compared to baseline. RESULTS: 64 patients randomized to calcium polystyrene sulfonate [n = 32] and control diet therapy [n = 32] groups. There were no differences between groups in general parameters including demographic data and the characteristics of concomitant disorders. The level of potassium observed at the visit of Day 5 of treatment reduced by 0.837 ± 0.475 mmol/L in calcium polystyrene sulfonate group and by 0.497 ± 0.409 mmol/L in the diet group; the differences between the groups were statistically significant (p = 0.0434). As a confirmation of the second end-point, ratio of reaching normal potassium level probability on Day 5 of treatment compared to diet therapy group was 1,45 (95% CI 1,04 - 2,03). CONCLUSION: calcium polystyrene sulfonate provides significant reduction of serum potassium in patients with hyperkalemia with chronic kidney disease (CKD) which are not requiring dialysis; it has the favorable safety profile and tolerability.

THE AIM: to ascertain whether aKlotho and FGF23 are associated with inorganic phosphate urinary excretion in early stages of chronic kidney disease (CKD). PATIENTS AND METHODS. The cross-sectional study included 80 patients (age 40.3±16.1) with primary immune glomerulopathies and estimated glomerular filtration rate (eGFR) range 30-140 ml/min/1.73 m². Serum levels of Pi (sPi), intact FGF23, intact PTH, serum αKlotho (sKlotho), urinary αKlotho creatinine ratio (uKlotho/uCr) were analyzed. Renal expression of αKlotho protein (rKlotho) was estimated by morphometric method. Evaluated parameters of renal Pi exchange including fractional excretion of Pi (FEPi) and 24h urinary Pi excretion (uPi24). RESULTS. There are no significant differences of sPi and uPi24 in groups of patients with eGFR 140-100, 99-70, 69-50 и 49-30 ml/min/1.73 m². The level of FEPi increased gradually along with fall of eGFR of 99-70 ml/min/1.73 m² (р<0.001). FEPi level significantly increased during decrease of eGFR (р<0,001). Compared to eGFR 140-100 ml/min/1.73 m² rKlotho expression in tubular epithelium was significantly lower at eGFR 99-70 ml/min/1.73 m², while sKlotho concentration decreased at eGFR 69-50 ml/min/1.73 m2. sKlotho concentration was significantly associated with eGFR, interstitial fibrosis, and glomerular sclerosis. During eGFR decrease the level of PTH increased significantly at eGFR 99-70 ml/min/1.73 m² compared to eGFR 140-100 ml/min/1.73 m². The level of FGF23 was significantly higher in patients with eGFR 49-30 ml/min/1.73 m². In patients with eGFR > 50 ml/min/1.73 m² no correlations were found between aKlotho/FGF23 and indices of Pi metabolism. FGF23 was associated with sPi in patients with eGFR < 50 ml/min/1.73 m². In the same groups FEPi was associated with PTH level. Neither Klotho nor FGF23 were associated with indices of urinary Pi excretion in multivariable regression analysis. sPi was independently associated with FGF23 (ß=0.50; р=0.007), while FEPi with PTH (ß=0.43; р=0.003). CONCLUSION. The decline of αKlotho in serum and kidneys occurs on early stages of CKD and apparently associates with tubulointerstitial injury preceding the increase of FGF23. In early stages of CKD the alterations in tubular reabsorption and renal excretion of Pi as important factor of this anion neutral balance support occur independently of circulating FGF23 and renal αKlotho.

THE AIM: to evaluate blood pressure (BP) level importance measured in different phases of “dialysis” week as a prognostic factor in hemodialysis patients. PATIENTS AND METHOD: correlation between BP level before, during and after dialysis in in-terdialytic interval and survival of patients was estimated in two years prospective study of one dialysis center. RESULTS: BP in most of patients decreases during dialysis session and continues to decrease in interdialysis interval. BP before first session was 146±24 and 85±14, second - 141±19 and 82±13, third - 141±23 and 84±15 mm Hg, being in target range (<140/90 mm Hg) in 57% of women and 48% of men. The interdialysis body mass gain (BM) was linked only with systolic BP measured before session (r=0.222; p=0.04), and diastolic BP measured at any time point, more closely - with predialysis values (r=0.454÷0.281; p<0.01). Two year survival (Kaplan-Meier) was not associated with predialysis and intradialysis BP; the association with postdialysis BP was close to significance in adjusted Cox regression model (p=0.051). Interdialysis BP higher 141 mm Hg (border of upper and middle tercile) was interrelated with mortality relative risk (RR) 3.23 (95%CI 1.08÷9.66); p=0.036. Regression model also included BM gain (RR=1.73 per 1% IWG), age (RR +7% per 1 year) and gender. Diastolic BP higher than 84 mm HG in interdialysis period was associated with increase of mortality level: RR=6.84 (95%CI 1.55÷30.2) p=0.011. CONCLUSION: BP in interdialysis period is significantly more important for survival than on dialysis.

THE AIM: to find operative intervention indicators are forming surgery risk factor of acute kidney injury (AKI) after aortofemoral reconstruction (AFR) and to predict individual creatininemia level in postoperative period. PATIENTS AND METHODS: We performed medical record of 82 patients with different forms of aortofemoral segment pathology, which had AFR surgical intervention in 2007 and 2008. For diagnose AKI we used AKIN (Acute Kidney Injury Network) score. All patients were dividing into to groups: group 1 (n=64) without AKI, and group 2 (n=18) with AKI. We used a descriptive statistics, correlation and regression statistical analysis. RESULTS: In patient which had had surgical intervention the real AKI rate was 21,9% (95% CI 11,7%>-32,1%>) in contrast with recorded cases of AKI (95% CI 0,9%>-8,4%>). Patient with AKI had higher (p<0,05) blood loss level in operation time and received more infusion therapy volume (blood cell reinfusion, blood components and colloid infusion). The regression model of maximum creatininemia level during 72 hours after aortofemoral reconstruction was shown. CONCLUSION: Operative risk factor with other factors is increasing a developing of AKI from patients undergoing aortofemoral reconstructions. The proprieties (speed and volume) of intraoperative blood loss are a main factor of this. The regression model, based on standard indicators (blood creatinin level before the surgical intervention, infusion therapy volume, aorta clamping time) will help to set a maximum level of creatinenemia during the first three days after reconstruction. Prediction of the maximum level creatinenemia in the postoperative period will provide an opportunity to advance to assume development AKI with a specific patient, which should attract additional attention to the medical staff in this category of patients.

AIM: To compare the efficacy of invasive interventions on parathyroid glands: parathyroidectomy (PTE) and local vitamin D injection therapy (LDIT) - in dialysis patients with secondary hyperparathyroidism (SHPT). PATIENTS AND METHODS: The effect size of invasive interventions on laboratory factors of mineral and bone damage CKD in comparison with the continuation of available conservative treatment in matched groups was evaluated for PTE (84 patients in treatment group and 105 - in control) and for LDIT (37 - in treatment group and 62 - in control). The effect size was evaluated for first month after intervention and in comparison between mean values for previous and following year. Treatment and control groups for each intervention were balanced by age, gender, dialysis duration, comorbidity, mineral and bone damage CKD parameters. The baseline PTH levels were 1250±556 pg/ml in PTE group and 921±356 pg/ml in LDIT group. RESULTS: The PTH level decreased by 1075±548 pg/ ml in PTE group. 38% of patients reached target range of PTH level (150-600 pg/ml) during the following year. The PTH level decreased by 347±360 pg/ml in LDIT group. 51% of patients reached target range of PTH level during the following year. The effect size was approximately equal to two pooled standard deviation (SD) of baseline PTH value for PTE and one SD for LDIT and remained stable for following year. The effect size concerning phosphate and alkaline phosphatase was compatible for PTE and LDIT, while concerning calciemia the effect size was significant only for PTE. CONCLUSION: Local vitamin D injection therapy in nodular hyperplasia (calculated gland volume < 0.5 sm3) with moderate PTH elevation (600-1000 pg/ml) are able to retard SHPT progression and improve mineral and bone disease CKD parameters in comparison with continuation of available conservative treatment. The effect size for LDIT is compatible with that for PTE in later stages of hyperplasia.

THE AIM. To create model of urate nephropathy in rats. MATERIAL AND METHODS. The study was performed on 25 male Wistar rats. To form urate nephropathy rats were administered oxonium and uric acid (UA) as part of standard laboratory mixture. Using biochemical and morphological techniques were evaluated changes obtained on days 7, 14, 21. RESULTS. During the experiment was noticed sequential growth of UA concentration in the blood plasma of animals. The concentration of uric acid in the urine and excretion of urates increased significantly. At the same time in the course of the experiment were recorded signs of kidney injury: increased excretion of protein in the urine, and also activity of several enzymes in urine. Picture of kidney injury characteristic for urate nephropathy was confirmed by histological examination results: already on the 7th day in renal tubular lumen defined urate deposits. CONCLUSION. The identified functional, biochemical and morphological changes allow to certify existence of urate nephropathy in long-term inhibition of uricase in rats, which can be considered as an adequate model of the corresponding human disease.

THE AIM: to study of renal function in rats, depending on the duration of administration of 6-propyl-2-thiouracil. MATHERIAL AND METHODS. Rats were administered 6-propyl-2-thiouracil orally every day for 7 or 25 days. Activity of kidneys was observed under condition of 5% water load, considering 5 ml of water to 100 g of body weight. RESULTS. It was established that renal function in rats depends on the duration of drug administration. In the early stages of the experiment, there is a moderate increase in the values of glomerular filtration rate, reduction of renal excretion of osmotically active substances, fluids and proteins, decrease in extracellular fluid osmolality. Long-term administration of the drug is accompanied by normalization of glomerular filtration rate, amd there is no significant increase in proteinuria, and a significant reduction in the excretion of osmotically active substances and the level of plasma osmolality. There were not found signs of toxic effects of propylthiouracil on the kidney activity in rats. CONCLUSION. The recorded changes in renal function caused by hypothyroid status and not related to the toxic effect of propylthiouracil on the activity of rat kidneys.

THE AIM: to analyze the results and estimation of efficacy of robot-assisted radical prostatectomy (RARP) in patients with prostate cancer (PCa). PATIENTS AND METHODS. Between 2010 and 2016 we performed 257 RARP in patients with PCa stage T1-T3aN0M0, Gleason 4-9, 48-78 years old with 11,5-155 ml prostate volume and 3,1-120 ng/ml general PSA level. We performed standard and modified RARP technique which included the preserving and reconstruction of periprostatic anatomical structures of pelvic. RESULTS. The operative time was 170±50 min, blood loss - 130±35 ml. There were no conversions, the intraoperative complications rate was 2,1%. Postoperative Clavien I-II rate - 21%, Clavien III - 3,5%, Clavien IV-V - 0%. Hospital stay was 12,0±4,2 days, urethral catheter removed on day 7-8. The continence rate was 91% and 98,6% after 1 and 12 months respectively, the potency recovery rate was 72% and 92% in 1 and 12 months respectively. The positive surgical margin rate was 14%. The “trifecta” and “pentafecta” were achieved in 87% and 52% respectively after 12 months. Five-years cancer-free survival rate, cancer-specific and overall survival rate were 94%, 100% and 97,5% respectively. CONCLUSION. Due to construction benefits of da Vinci robotic system we may now achieve preserving, reconstruction and enhancing of periprostatiс anatomical structures which are participated in continence mechanism. The improving of RARP technique should contribute to early continence recovery in patients with PCa.

The lecture presents the prevalence of urolithiasis, the possible causes of incidence rate, role of uric acid metabolism disorders in the genesis of nephrolithiasis, pathological changes of kidneys due to metabolism disorders of uric acid. Therapy of kidney stones is not limited by calculi removal, and includes the correction of metabolism to prevent growth and recurrence of lithiasis. In this aspect, are considered inhibitors of xanthine oxidase, uricosuric medications, citrate drugs. A special place is given to the frequency and characteristics of urate nephrolithiasis, modern possibilities of its comprehensive diagnostics and therapy. Discussed in detail citrate litholytic therapy with individual selection of doses, the use of herbal remedies, dietary treatment, ways of urate nephrolithiasis prevention.