REVIEWS AND LECTURES
In recent decades, the main pathogenetic mechanisms for maintaining muscle mass and strength have been discovered. Most of the scientific papers on the molecular aspects of the pathogenesis of sarcopenia were focused on the Akt-signaling pathway. The subject of the study were people of elderly and senile age, immobilized patients, patients with CKD 1-4 stages, animals. However, recently more attention has been paid to the role of protein – the mammalian target of rapamycin mTOR. It seems to be a key link in the control of muscle mass and is a promising marker in understanding the mechanisms of the pathogenesis of sarcopenia. Its importance in protein metabolism in patients with end stage kidney disease is not studied and requires further research. The presented scientific review contains information on the role of mTOR and its components – mTORC1 and mTORC2 in maintaining muscle mass and strength in a healthy person and in the formation of sarcopenia in patients with CKD. The general aid of mTORC1 complex is regulation of protein production which is necessary for cell growth and differentiation. mTORC2 complex functions are not enough studied. It is established that it plays important role in such biological processes as cytoskeleton organization, intracellular homeostasis maintaining, so it provides cell resistance and cell survivability in negative external and internal impulses. mTOR protein can be considered as promising molecular marker in diagnostics of protein metabolism early disturbances in patients with CKD and also as additory factor of sarcopenia severity assessment.
Кidney injury is a frequent and significant complication of cancer and cancer therapy. The kidneys are susceptible to injury from malignant infiltration, damage by metabolites of malignant cells, glomerular injury, nephrotoxic drugs including chemotherapeutic agents. Also bone marrow transplantation complications, infections with immune suppression (including septicemia), tumor lysis syndrome should be taken into account. Chemotherapeutic agents are a common cause of acute kidney injury but can potentially lead to chronic kidney disease development in cancer patients. This article summarizes risk factors of acute kidney injury in cancer patients. Risk factors are divided into two groups. The systemic are decrease of total circulating blood volume, infiltration of kidney tissue by tumor cells, dysproteinemia, electrolyte disturbances. The local (renal) risk factors are microcirculation disturbances, drugs biotransformation with formation of reactive oxygen intermediates, high concentration of nephrotoxic agents in proximal tubules and its sensitivity to ischemia. Drug-related risk factors include: drugs combination with cytotoxic effect high doses long term use necessity, direct cytotoxic effect of not only chemotherapeutic agents but also its metabolites, mean solubility forming intratubular precipitates. Early diagnosis, timely prevention and treatment of these complications provide significantly improve nononcologic results of treatment.
ORIGINAL ARTICLES. CLINICAL INVESTIGATIONS
Currently, accumulated a large amount of data on the role of inflammation in the vascular endothelium damage during the development of the chronic forms of many diseases. THE AIM: identification of endothelial dysfunction (ED) biomarkers as early predictors of CKD development in patients with chronic lung diseases. PATIENTS AND METHODS. 123 patients with COPD aged 55-79 years were examined, studied features of clinical and anthropometric parameters, data of the main biochemical systemic inflammation markers and vascular endothelial dysfunction, their significance in the development of chronic kidney disease (CKD). RESULTS. For the first time CKD was diagnosed in 51.2% of patients with COPD. In comorbid patients with COPD and related CKD noted more severe course of disease. Also in these patients detected significantly elevated endothelial dysfunction indices. CRP and fibrinogen levels were higher in all patients with COPD and authentically correlated with disease severety. Direct correlation between CRP and TNF-α levels was revealed. Noted that tumor necrosis factor was higher in smoker patients with COPD. Markers of kidneys endothelial dysfunction – homocysteine, IL-6, IL-8 – were significantly higher in patients with decreased GFR. Also in these patients were detected increased levels of serum creatinine and urea. Creatinine clearance inversely correlated with homocysteine plasma level. In all cases of fibrinogen increase in patients with COPD. Homocysteine level was also increased, but in combination with CKD it was significantly higher: respectively 19,8±7,51 and 39,8 ± 7,14 μmol/L, p<0,005. CONCLUSION. The received information confirms the hypothesis about the relationship of ED biomarkers homocysteine, TNF-α, IL-6, IL-8 with the development of chronic kidney disease in comorbid patients with COPD.
THE AIM: to investigate the role of the podocin in the progression of renal dysfunction in diabetic nephropathy (DN) in patients with diabetes mellitus (DM) type 2.
PATIENTS AND METHODS. The study was open, controlled with parallel design in patients with DM type 2 and with CKD 1-3a. The duration was 4 years. Standard methods for the assessing of hormonal and metabolic profile of the blood and functional activity of kidneys were performed in patients groups and control group. The primary endpoint is the dynamics of podocinuria in patients on the basis of the ELISA.
RESULTS: The study included 119 patients (61 men and 58 women) with Diabetes mellitus type 2. Diabetic nephropathy. CKD 1-3a. Patients were divided into 3 groups: group 1 – 37 patients with CKD Stage 1; group 2 – 47 patients with CKD Stage 2; group 3 – 35 patients with CKD Stage 3a. Control group – persons without DM and kidney injury (n=30). The participation of podocin in renal functional activity regulation (dynamics of mean values and correlations with albumin excretion rate and GFR) and hormonal and metabolic interactions (dynamics of mean values of fasting glycemia, OGTT, Hb1Ac, C-peptide, creatinine, potassium, total cholesterol, LDL-C, atherogenic index and their correlations with podocinuria) was shown in patients with DM type 2 and DN.
CONCLUSION: podocinuria interrelations with the indices of kidneys functional activity, hormonal and metabolic profile of the blood helps to detail the molecular mechanism of development of ND in type 2 diabetes. Podocin is promising biomarker of CKD 1-2 stages with type 2 DM.
Acute pyelonephritis (AP) is an inflammatory and infectious process that occurs due to immunological disorders, occurring mostly in the calyx-pelvic renal system and the tubulointerstitial zone. Pyelonephritis more often occurs in women of reproductive age.
THE AIM: to study genetically determined changes in the Toll-like receptor 4, mutations in the genes of interleukin 1β, interleukin 6 in women of reproductive age with acute pyelonephritis.
PATIENTS AND METHODS: The study included 26 women with acute pyelonephritis. Control group consisted of 27 practically healthy women comparable ages and without infections of kidneys and urinary tract in anamnsis. The presence of polymorphism of T (-31) C genes IL-1β, C (-174) G IL-6 and Arg299Gly TLR4 was revealed by PCR.
RESULTS: Women of reproductive age with acute pyelonephritis have a high prevalence of polymorphism of IL-1β and TLR4 genes. Genotypes of TT and CT and also polymorphism of the T (-31) C gene of IL-1β and the genotype of the GG polymorphism of the gene Asp299Gly TLR-4 were associated with an increased risk of inflammatory infectious process in the kidneys. In healthy individuals, CC genotypes are found for the T (-31) C gene of IL-1β and AA for the Asp299Gly TLR4 gene.
CONCLUSIONS: It is useful for women of reproductive age to provide genetic diagnostics to detect reference genes polymorphism. It will allow to reveal AP development risk group for carrying out primary prevention.
THE AIM. To determine the concentration of natriuretic peptide in the blood serum in children with congenital malformations of the urinary system (CM US) and to compare with the activity of renin-angiotensin-aldosterone system (RAAS).
MATERIALS AND METHODS. 119 patients with CM US aged 3 to 18 years were examined. A control group of 10 clinically healthy children. 3 groups were assigned: group I – 55 children with congenital vesicoureteral reflux, and group II – 34 children with congenital hydronephrosis and ureterohydronephrosis, III group – 30 children with other forms of dysembryogenesis of the US. Following indicators were identified by ELISA in the blood: renin, aldosterone, N – terminal propeptide natriuretic hormone (NT-рroВNР).
RESULTS. NT-рroВNР, renin and aldosterone hyperproduction were diagnosed in 59,6%, 69,7%, 54.6 % of sick children relatively. Concentrations were higher in all variants of malformations in comparison with the control group. Significant differences were revealed in obstructive species, where arterial hypertension (AH) was diagnosed more often. Patients with AH recorded significantly higher concentrations of NT-proВNР and renin.
CONCLUSION. The key point in pathological processes development
and progression in the cardiovascular system and kidneys is the activation of RAAS. The system of natriuretic factors is important in maintaining the compensated state of patients due to the blockade of RAAS.
THE AIM: to evaluate the role of laboratory obesity markers in the progression of chronic kidney disease (CKD) and the development of cardiovascular complications in patients with arterial hypertension (AH) and obesity.
PATIENTS AND METHODS. 120 patients with AH stage II-III aged from 45 to 70 years with unachieved target blood pressure values (BP) were divided into four comparable in sex, age, frequency of smoking occurrence, hypertension duration, the level of office systolic AD (SBP) and diastolic blood pressure (DBP) groups depending on the body mass index (BMI). We performed physical examination, evaluated the renal function, laboratory markers of obesity, analyzed the combined risk of CKD progression and the development of cardiovascular complications.
RESULTS. There was a significant increase in the level of proteinuria (PU) and albuminuria (AU) among the patients in groups 3 and 4 compared with group 1 (301.3 [138.1, 691.0] and 305.7 [139.4, 646.9] vs 101.3 [47.9, 116.9] mg/g; 91.0 [65.9, 273.5] and 119.2 [91.0, 291.2 vs 42.2 [41.3; 51.1] mg/g, respectively), as well as a statistically significant decrease in the glomerular filtration rate (GFR) in patients of groups 3 and 4 compared with patients in group 1 (63,53,73 and 61,22,71 vs 72 [ 64; 98] mL / min / 1.73 m2). Serum leptin concentration increased from group 1 to group 4 (significant differences were found between groups 2,3,4 in comparison with group 1 and between group 4 in comparison with group 2), while the concentration of adiponectin decreased from group 1 to group 4 (the differences were significant between groups 2,3,4 in comparison with group 1). A statistically significant inverse correlation between GFR and leptin concentration (r = -0.42), a direct correlation between the concentration of adiponectin and GFR (r = 0.36), the inverse relationship between the concentration of adiponectin and PU (r = -0.33), AU (r = -0.24) were found.
CONCLUSION. The study showed a statistically significant progressive deterioration in the renal function, as well as an increase in the combined risk of progression of CKD and the development of cardiovascular complications in AH patients with an increase in obesity with comparable values of office SAP and office DAP among the studied groups. The revealed reliable correlation interrelations between the parameters of renal function and obesity markers testify to the important pathogenetic role of leptin and adiponectin in the development and progression of CKD in patients with AH and obesity.
THE AIM. To assess quality of life (QOL) of hemodialysis (HD) patients using the Kidney Disease Quality of Life Short Form (KDQOL-SFTM) questionnaire including specific for dialysis therapy sections.
PATIENTS AND METHODS. The KDQOL-SF questionnaire was administered to 192 HD patients. RESULTS. It was shown that HD patients experienced low satisfaction with the employment – 0,0 [0,0–50,0] (Me[IQR]) on the scale of «work status». A low score on the scale of "burden of kidney disease" was registered – 31,3 [18,8–50,0]. The highest scores were obtained on the scales of «cognitive functioning» 86,9 [66,7–93,3], «quality of social interaction» – 80,0 [66,7–93,3], «social functioning» – 62,5 [50,0–87,5], mental health – 60,8±18,1 (M±SD). Among the most significant stress factors – limited ability to travel and fluid restriction (74% and 66% of patients, respectively). The most bothersome problems were muscle soreness (50% pateients), fatigue (45%), dizziness (44%), itchy skin (41%), shortness of breath (40%), dry skin (34%).
CONCLUSION. The KDQOL-SFTM questionnaire which takes about 20 minutes to complete provides important information about the limited opportunities and major concerns of dialysis patients.
Chronic glomerulonephritis is characterized by irreversible progression of the pathological process, which leads to the formation of terminal renal failure significantly impairing the patient's quality of life, leading to internal dysfunction and increasing the risk of premature overall and cardiovascular mortality. Consequently, the search for non-invasive methods for assessing the state of renal tissue, including the detection of proteins involved in renal inflammation, fibrosis, intercellular interaction is currently important.
THE AIM: To determine the serum levels of the vascular cell adhesion molecule-1 (VCAM-1) in patients with various forms of chronic glomerulonephritis (CGN) and to clarify its relationship to the development of morphological changes in the renal tissue.
PATIENTS AND METHODS: In 80 patients (men and women), with CGN in the acute stage was carried out a detailed clinical and laboratory examination, including determination of serum VCAM-1 by ELISA and performing puncture renal biopsy with the assessment of morphological changes. Statistical analysis of the results was carried out using «Microsoft Office Excel 2010» («Microsoft Corp.», USA) and "STATISTICA 10.0" («StatSoft Inc.», USA).
RESULTS. The serum level concentration of VCAM-1 was 719 [643;771] ng/ml. Obtained statistically significant interrelations with enlargement of mesangial space, endothelial growth, capillary walls thickening, mesangial hypercellularity, endothelial hypercellularity, protein casts in tubules, anses capillaries union, fibrose demilunes, podocyte necrosis, hypertrophic remodeling type of resistive type vessels, Ig deposites, IgA deposites, IgG seposites, C3 complement fluorescence, fibrinogen deposites.
CONCLUSION: The results of the study demonstrate the important role of VCAM-1 in the development of immunocomplex inflammation in glomerulonephritis. VCAM-1 is a marker of different morphological changes in CGN, and determining the level of VCAM-1 in serum is informative, simple and noninvasive method which provides evaluation of inflammatory process activity, prediction of the risk of morphological changes in the renal tissue structure in patients with CGN.
THE AIM: to evaluate the effectiveness of complex immunomodulatory therapy of vulvovaginitis in preschool children with urinary tract infection (UTI) by studying the features of vaginal microbiocenosis and immune status.
PATIENTS AND METHODS. Prospective controlled randomized study was conducted in 94 girls aged 3-6 years with vulvovaginitis, of which 1 group (n=52) – vulvovaginitis with urinary tract infections; 2 group (n=42) – girls with isolated vulvovaginitis. 2 types of treatment were used: standard treatment and treatment with immunomodulatory drug comprising a recombinant interferon alpha-2b and high-level antioxidants – ascorbic acid and alpha- tocopherol acetate.
RESULTS. Microscopic examination revealed type III vaginal smear in all patients. In 1-st group frequency of Gardnerella vaginalis, Esherichia coli, Сandida albicans isolation increased, in 2-nd group – Staphylococcus epidermidis, Enterococcus faecalis (microbial content more than 105 cfu/ml). In reviewing basic immunogram in girls og 1-st group revealed decrease of total content of CD3+CD8+- lymphocytes (0,82 [0,79;0,99]×109/l vs 1,27 [1,01;1,44]×109/l, p<0,05), CD3-CD16+CD56+-lymphocytes (0,29 [0,26; 0,32] × 109/l vs 0,48 [0,41; 0,5] × 109/l, p<0,05), CD3-CD19+-lymphocytes (0,54 [0,5;0,61] × 109/l vs 0,98 [0,91;1,14] × 109/l in control, p<0,05). After complex treatment in 1-st group decreased microbial colonizations of E.coli from 6,8±0,05×106 to 1,7±0,03×102 cfu/ml, р<0,05; in2-nd group – Staphylococcus epidermidis from 3,6±0,02×106 to 1,5±0,2×102 cfu/ml, р<0,05, and in vaginal smear noted normocenosis.
CONCLUSION. Anti-inflammatory therapy of vulvovaginitis in girls with urinary tract infections, including the use of a complex antiviral immunomodulatory drug containing recombinant interferon α2b and highly active antioxidants – ascorbic acid and alpha tocopherol acetate improves the condition of the vaginal biotope, immune status, reduces the rates of microbial colonization, number of vulvovaginitis relapses.
THE AIM: to study the peculiarities of physical and sexual development of adolescent girls with recurrent urinary tract infections.
PATIENTS AND METHODS. Examined 70 adolescent girls aged 16 – 18 years with exacerbation of chronic pyelonephritis (CP): 1 group (n=43) – with rare relapse history (relapses pyelonephritis from 1 to 3 times during the period of the disease, rCP) and group 2 (n=27) with frequent relapses (more than 3 times a year, fCP). The control group (n=30) consisted of practically healthy adolescent girls of the same age. Anthropometry, evaluation of sexual development, specialized gynecological examination, determination of serum hormones, ultrasound examination of the reproductive organs were carried out. Statistical processing of research results was performed using the software packages Statistica 6.0 ("StatSoft Inc", USA) and statistical analysis Microsoft Office Excel 2003" ("Microsoft Corporation", USA).
RESULTS. It was revealed that in patients with rCP, compared with girls of the 1st and control groups, there was a lower growth, a decrease in the basic pelvic dimensions, against the background of a tendency to increase weight, there were some variants of sexual disorders, more often than in other groups there were early pubarche and later menarche. Established significant increase in the level of LH, testosterone and DHEA-S in the background of hypoprogesteronemia. The rate of hyperpolymenorrhea, uterine bleeding and primary oligomenorrhea was significantly higher, were often found emerging polycystic ovary syndrome and chronic vulvovaginitis.
CONCLUSION. Patients with frequent recurrence of urinary tract infections have a variety of constitutional features, a tendency to metabolic syndrome development, expressed hormonal status violations. The detected increase in testosterone levels contributes to the emerging polycystic ovaries syndrome development.
ISSN 2541-9439 (Online)