LEADING ARTICLE
Over the past two decades, the concept of the epithelial to mesenchymal transition (EMT) has been imported from embryology and oncology to fibrosis, particularly in the kidney. This interest in EMT in the context of renal fibrosis stems from observations of epithelial cells undergoing phenotypic changes reminiscent of fibroblasts. Whether EMT is actually a source of interstitial fibroblasts has been the subject of heated debate, and this controversy has caused physicians to neglect the value of EMT as a biomarker in renal fibrosis. In this review, we describe the evolution of the techniques used to detect EMT during fibrosing renal diseases, and what information they provide in the diagnosis of various renal diseases. Highlighting the great heterogeneity of these techniques and the need to standardize them, we warn against some misleading uses of EMT markers. We suggest using the association of vimentin and β-catenin for the diagnosis of EMT in renal pathology because it is both sensitive and prognostic, thus satisfying the properties required for a screening test. Finally, we discuss the potential interests to diagnose EMT for the comprehension of renal fibrosis and for clinical practice.
REVIEWS AND LECTURES
The importance of the metabolic syndrome (MS) in the global prevalence of chronic kidney disease (CKD) has led to numerous international studies, which showed a close association of this syndrome pathogenesis platform – insulin resistance (IR) and compensatory hyperinsulinemia (HI) – with a glomerular filtration rate (GFR) at the very early stages of nephropathy. Based on these data, it was suggested that therapy aimed at reducing IR may slow the progression of CKD. We have investigated a potential effect of IR correction on the course of nephropathy and on the CKD risk factors, associated with IR. IR correction in these studies was attended by improve of parameters such as waist circumference, body mass index, HOMA-IR, HDL, triglycerides, hyperleptinemia, adiponectin deficiency, with contemporary normalization of renal activity indexes (decrease of hyperfiltration, microalbuminuria and increase of GFR level in patients with decreased filtration capacity of kidneys). The data indicate that correction of IR has a positive effect on many risk factors of nephropathy development and can prevent or slow the progression of CKD in patients with metabolic syndrome.
In the literature review there are features of classification, etiology and clinical manifestations, results of injury biomarkers study (NGAL, IL-18, KIM-1) and biomarkers of function (concentration of creatinine and serum cystatin C, glomerular filtration rate), treatment and outcome of acute kidney injury in children.
The review gives an idea of impact of some molecular mechanisms of apoptosis on the development of nephropathies of various origins. Ways of realization and contribution of molecules (р53, PUMA, MDM2, р21) in renal disease associated with glomerular injury, ischemia, in the development of renal failure and their participation in the progression and prognosis of renal disorders were described. A subtle mechanism of the effect of the molecule р53 on cancerogenesis is revealed. The expression of р53 protein defines a nephrotoxicity of a number of chemotherapeutic drugs. Changes and influence of a proapoptotic protein PUMA were defined only in a context of cancerogenesis and nephrotoxicity. The role of a molecule MDM2 as predictor of cancerogenesis and clinical course of lupus nephritis is considered. Role of molecule MDM2 as a predictor of neoplastic proliferationand evolution of lupus nephritis was studied. The senescence marker, р21 molecule makes a contribution to development of acute renal failure, focal-segmental glomerulosclerosis, diabetic nephropathy, autoimmune disorders in kidneys. Recognizing apoptosis as one of mechanisms in development of kidney diseases, this review gives strong incentive for further research and discovery of innovative approaches for prevention, prognosis and treatment of nephropathies.
Peroxisome proliferator-activated receptors (PPAR), nuclear transcription factors from family of hormonal receptors, carry out control above a carbohydrate and fatty acid metabolism, energy homeostasis, activity of the immune system, inflammation and endothelia of vessels. All of three types of PPAR‘s are expressed in kidney and play an important role in physiology and pathology of these organs, executing renoprotective action by inflammation, diabetes mellitus nephropathy, acute renal failure, glomerulonephritis and other damages.
Adequate control of hydration plays an important role in the treatment of dialysis patients. Well known that chronic fluid overload causes hypertension and left ventricular hypertrophy, however dehydration can be associated with intradialysis complications. Hyperhydration and dehydration associated with increased morbidity and mortality in patients on dialysis. The exact definition of the state of hydration in dialysis patients remains a challenge, and is based on clinical criteria and unavailability of accurate measuring instruments. Bioimpedance spectroscopy method determines the state of hydration and body composition, which reliability had been confirmed by isotopic dilution and other reference methods for the determination of body composition.
ORIGINAL ARTICLES. CLINICAL INVESTIGATIONS
THE AIM of the study was to reveal chronic kidney disease (CKD) risk factors and degree of albuminuria (AU) in different age groups applying to Health Centers in the Moscow Region of Russia and also improvement of its association with different CKD risk factors. METHODS. 1623 subjects (390 (24%) men and 1233 (76%) women, age 18-85 years) were studied. The participants were divided into two age groups: younger participants (age 50 in men and >55 in women). AU was evaluated by dipstick test in casual urine samples. We developed questionnaire collecting information about health complaints, lifestyle, medical and family history. RESULTS. In elderly participants (age >50 in men and >55 in women) AU>30 mg/L was found in 48%, and in younger participants in 39%, р30 mg/L was significantly associated with edema (66,7%), dyspnea (63,2%), palpitation (56,4%), chest pain (83,3%), thirst (73,7%), history of proteinuria (67,5%), history of ultrasound CKD signs (47,4%), obesity (56,2%), smoking (46,4%), low physical activity (34,0%).History of hyperglycemia and diabetes, history of hypertension, hyperlipidemia, family history of CKD, family history of diabetes was associated with high level of AU in both age groups. CONCLUSION. Our data reflect high prevalence of AU>30 mg/L in elderly population. Different age groups are characterized by features of high AU risk factors, which should be taken into the national screening program.
AIM: to study frequency and risk factors of AKI and also features of its clinical course in the postoperative period in patients undergoing CABG in a planned order. PATIENTS AND METHODS. 548 patients (331 men and 217 women) aged from 42 to 68 years (57,9±8,3 years) were examined before and after CABG by cardiopulmonary bypass. A serum creatinine (sCr) levels and glomerular filtration rate were defined before operation, daily within 7 days after CABG, at discharge from the hospital and in 3 months after discharge. AKI was diagnosed and classified by level of sCr using criteria of RIFLE. RESULTS. AKI was diagnosed in 132 patients (24,1%) after CABG, out of them 109 patients (19,9%) had mild AKI, 64 patients (11,7%) – moderate AKI and 29 patients (5,3%) – with severe AKI. Also transient AKI was revealed in 58,3% of the cases, persistent AKI – in 39,4% of the cases and resistant AKI – in 2,3% of the cases. Renal replacement therapy (hemodialysis) was performed in 7 patients (36,8%). An in-hospital mortality among patients with and without AKI was 7,6% and 2,2% respectively (χ2 = 7,23; p = 0,007). CONCLUSION. Thus, sCr levels in patients with AKI were associated with such factors as characteristics of severity of CABG surgery, comorbid conditions such as congestive heart failure, hypertension, atrial fibrillation and age higher than 60 years.
THE AIM OF THE RESEARCH. Determine cerebro-renal relationship between the early signs of cerebral atherosclerosis and the level of the calculated glomerular filtration rate (GFR) with account of the influence of risk factors cerebrovascular diseases in elderly and senile patients of the Republic of Sakha (Yakutia), suffering from chronic brain ischemia (CBI) depending on the environmental and climatic conditions of region of residence. PATIENTS AND METHODS. The study included 245 patients from 60 to 89 years, comparable by age and sex, were divided into two groups according to region of residence (Arctic and South), for two age groups (elderly and senile age) and by the sex (male and female). The main method of the study of cerebral hemodynamics in this work has been ultrasound Doppler Sonography (UDSG). Doppler sonography with color scanning and spectral Doppler analysis of the brachiocephalic arteries on extracranial level was performed according to standard method for ultrasound systems ACUSON «Sequoia-512» sensor linear format of the generated frequency of the ultrasonic signal 4 and 8 MHz in the permanent-wave mode. All patients were investigated the functional state of the kidneys. GFR, was determined by the formula MDRD with subsequent determination of the stages of chronic kidney disease. RESULTS. The direct positive correlation between the thickness of intimate-media (ТIМ) and the average of the GFR, and also found a statistically significant relationship between risk factors in the onset and progression of CKD and CBI, dependent on environmental and climatic conditions of region of residence. CONCLUSION. Features of cerebro-renal relations in persons of elderly and senile age in the Republic of Sakha (Yakutia) are caused by environmental and climatic conditions of region of residence.
AIM OF RESEARCH: Analysis and prognosis of adverse renal outcomes in elderly patients after cardiopulmonary bypass surgery by RBF-neural networks. MATERIALS AND METHODS: a prospective cohort study was performed in 81 patients 65 to 80 years. Investigated a range of demographic, perioperative, biochemical factors as possible significant predictors of acute renal injury and decline of glomerular filtration rate (GFR) in elderly patients avail oneself regression analysis. Set that the significant predictors of AKI are the number of affected organs, the category of diagnosis, the time of surgery, level of lipocaline-2 (NGAL) after cardiac surgery, duration of mechanical ventilation. Significant predictors of GFR decline are the initial concentration of serum creatinine, body mass index, stage of AKI (criteria RIFLE), age, time of surgery and cardiopulmonary bypass. CONCLUSION: based on these data, prediction models of adverse renal outcomes (AKI and decline of GFR) was proposed putting to use the RBF – neural networks.
THE AIM: to study the effect of plasmapheresis on the initial function and intraorganic blood flow of renal graft in the early postoperative period. PATIENTS AND METHODS: we evaluated the results of treatment of 60 renal transplant recipients. The patients were divided into two groups: in 30 recipients of group 1 we applied plasmapheresis with replacement from 1,4 to 3,7 liters of plasma and in 30 recipients of control group we have not performed plasmapheresis. RESULTS: intraorganic hemodynamics clearly reflects the functional state of the transplanted kidney. High resistive index (Ri> 0,9) is an informative diagnosis criterion of acute tubular necrosis and it’s also indicates an inadequate blood supply to the kidneys. Plasmapheresis has expressed positive effect on renal hemodynamics, initial graft function, glomerular filtration rate, the duration of azotemia normalization period. Immediate graft function in patients of group 1 was observed in 26 patients, whereas in the group 2 – only in 14. There were no patients with initial non-functioning graft in group 1, while in group 2 there were two such patients. CONCLUSION: plasmapheresis performed in the early postoperative period (not later than 3-5 hours after reperfusion of the graft) has an expressed positive effect on the functional state of the transplanted kidney.
The study of a group of patients with IgA-nephropathy (IgAN ) was performed with detailed analysis of inflammatory and sclerotic changes in the tubuloinetrstitium (TIN). As well as immunohistochemical analysis of activity C4d – MBL activation marker of complement pathway. Quantitively and and semiquantitatively were estimated immunoglobulins (IgG, IgM, IgM), complement fractions C1q, C3c, fibrinogen, kappa light chains and lambda deposition, the number of TIN microvessels with – C4d – positive reaction in endothelium. Extracapillary proliferation, global and segmental sclerosis, mesangial proliferation, interstitial fibrosis, the number of peritubular capillaries in the TIN with leukocytes-peritubular capillaritis (PTC), the age, sex, daily proteinuria and serum creatinine, glomerular filtration rate (GFR) by MDRD were evaluated. As a result we have obtained the data about inflammatory activity in TIN microvessels of some patients under IgAN that may signify the partial activation the lectin complement pathway and the more severe clinical course.
JOURNAL IN THE JOURNAL. ACTUAL PROBLEMS OF UROLOGY
THE AIM – to improve the quality of treatment of patients with large upper ureteral stones. Comparison of treatment results of 86 such patients in different ways was carried out. In 29 of them (34.11%) the treatment was started with extracorporeal shock wave lithotripsy, in 19 (21.35%) patients – contact lithotripsy. In some cases it was enough to remove calculus, in some we had to start additional methods of treatment. The third group, 38 patients (44.54%), was performed only endovideosurgery ureterolithotomy. The article represents results of comparing the efficiency of mentioned treatment methods based on comparison of the functional state of kidneys, pyelonephritis activity, duration of hospital stay, required repeated interventions and analysis of complications, depending on the size of stone and duration of its stay in the same place. Statistically it is proved that at large upper ureteral stones endovideosurgical ureterolithotomy is more preferably than contact and extracorporeal lithotripsy. Long term stay of the stone on the same place increase complications risk and necessity of reinterventions after extracorporeal lithotripsy and contact lithotripsy can’t be recommended for treatment of this group of patients.
PRACTICAL NOTES
Extraskeletal calcification is frequent and severe complication in chronic hemodialysis patients. Uremic tumoral calcinosis is the massive calcium deposits in periarticular tissues, usually around large joints. We report the clinical, roentgenographic, tomographic and ultrasound imaging findings and describe pathology results in a case of severe metastatic calcification of periarticular tissues in a patient on chronic hemodialysis due to hyperphosphataemia and increased calcium-phosphorus product.
ISSN 2541-9439 (Online)