Urinary indicators of inflammation and fibrosis in children with congenital uropathies
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01.09.2018 |
Morozov D.
Morozova O.
Maltseva L.
Lakomova D.
Palatova T.
Morozov K.
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Pediatriya - Zhurnal im G.N. Speranskogo |
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© 2018; Pediatria Ltd. All rights reserved. Congenital uropathies (CU) are anomalies associated with impaired patency of the upper and lower urinary tract and include congenital hydronephrosis, megaureter, primary vesicoureteral reflux (VUR), infravesical obstruction with prevalence in the pediatric population up to 1,4-2,8%. The most dangerous complication of CU is the development of kidney fibrosis in 30-60% of children combined with a persistent urinary system infection (USI). The lack of effective methods for early diagnosis and evaluation of renal parenchyma fibrosis treatment efficacy dictates the need for further search for molecular indicators of kidney injury. The article describes the study of inflammation biomarkers (interleukin 6 (IL6), inertleukin 8 (IL8), interleukin 10 (IL10)) and fibrosis (monocyte chemoattractant protein 1 (MCP1), transforming growth factor Β1 (TGFΒ1), vasculoendothelial growth factor (VEGF)) in urine in children with CU for diagnosis, monitoring and predicting the course of pathology. The study included 255 patients with various variants of CU (congenital hydronephrosis - 75, VUR - 169, infravesical obstruction - 11). The mean age of the patients was 4,3±3,2 years. The comparison group included 20 almost healthy children stratified by sex and age without USI. Biomarkers were determined by the method of enzyme immunoassay (ELISA) in the dynamics of pathology. All patients had an increase in urinary levels of proinflammatory cytokines (IL6, 8), even without clinical picture of USI. The increase in the concentration of MCP1 and TGFΒ1 in the urine is proportional to the degree and duration of VUR before its treatment, their content increased after 6 months after the correction of VUR and indicated the persistence of latent pyelonephritis and fibrosis progression. Molecular diagnosis of inflammation and fibrosis markers n the urine is a promising noninvasive method for assessing the pathological process in kidneys, the effectiveness and adequacy of the treatment.
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Mechanisms of LPS-induced acute kidney injury in neonatal and adult rats
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08.08.2018 |
Plotnikov E.
Brezgunova A.
Pevzner I.
Zorova L.
Manskikh V.
Popkov V.
Silachev D.
Zorov D.
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Antioxidants |
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© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Neonatal sepsis is one of the major causes of mortality and morbidity in newborns, greatly associated with severe acute kidney injury (AKI) and failure. Handling of newborns with kidney damage can be significantly different compared to adults, and it is necessary to consider the individuality of an organism’s response to systemic inflammation. In this study, we used lipopolysaccharide (LPS)-mediated acute kidney injury model to study mechanisms of kidney cells damage in neonatal and adult rats. We found LPS-associated oxidative stress was more severe in adults compared to neonates, as judged by levels of carbonylated proteins and products of lipids peroxidation. In both models, LPS-mediated septic simulation caused apoptosis of kidney cells, albeit to a different degree. Elevated levels of proliferating cell nuclear antigen (PCNA) in the kidney dropped after LPS administration in neonates but increased in adults. Renal fibrosis, as estimated by smooth muscle actin levels, was significantly higher in adult kidneys, whereas these changes were less profound in LPS-treated neonatal kidneys. We concluded that in LPS-mediated AKI model, renal cells of neonatal rats were more tolerant to oxidative stress and suffered less from long-term pathological consequences, such as fibrosis. In addition, we assume that by some features LPS administration simulates the conditions of accelerated aging.
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Parameters of vancomycin pharmacokinetics in postoperative patients with renal dysfunction: Comparing the results of a pharmacokinetic study and mathematical modeling
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01.01.2018 |
Ramenskaya G.
Shokhin I.
Lukina M.
Andrushchishina T.
Chukina M.
Tsarev I.
Vartanova O.
Morozova T.
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Bulletin of Russian State Medical University |
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© 2018 Pirogov Russian National Research Medical University. All rights reserved. Mathematical modeling of pharmacokinetic (PK) and pharmacodynamic (PD) parameters essential for establishing correct dosing regimens is an alternative to pharmacokinetic studies (PKS) adopted in the clinical setting. The aim of this work was to compare the values of PK parameters for vancomycin obtained in an actual PKS and through MM in postoperative patients with kidney injury. Our prospective study included 61 patients (47 males and 14 females aged 60.59 ± 12.23 years). During PKS, drug concentrations at steady state Сtrough and Cpeak were measured by high-performance liquid chromatography followed by the calculation of the area under the plasma concentration-time curve AUC24. For mathematical modeling, a single-compartment model was employed; PK parameters were estimated using R 3.4.0. The values of Ctrough measured 48 h after the onset of antibiotic therapy during PKS were significantly lower than those predicted by MM (р = 0.004). In a group of patients with acute kidney injury (AKI), AUC24 measured at the end of treatment was significantly higher than its value predicted by MM (р = 0.011). The probability of achieving the target AUC24 to MIC ratio of over 400 µg•h /ml is higher in the group of patients with Ctrough = 10–15 µg /ml. Our findings confirm that the use of MM in postoperative patients with renal dysfunction is limited and therapeutic drug monitoring should be used instead.
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Mechanisms of nephrosclerosis development in children with vesicoureteral reflux
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01.01.2018 |
Morozova O.
Litvitskiy P.
Morozov D.
Maltseva L.
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Vestnik Rossiiskoi Akademii Meditsinskikh Nauk |
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© 2018 Izdatel'stvo Meditsina. All rights reserved. The review discusses the issue of reflux nephropathy for specialists of the system of higher medical education: the article provides the definition, characterizes the epidemiology, risk factors for disease development in children with vesicoureteral reflux, causes and molecular mechanisms of renal fibrosis formation and progression in reflux nephropathy, markers for diagnosing and predicting the disease course.
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Mechanisms of nephrosclerosis development in children with vesicoureteral reflux
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01.01.2018 |
Morozova O.
Litvitskiy P.
Morozov D.
Maltseva L.
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Voprosy Sovremennoi Pediatrii - Current Pediatrics |
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© 2018 Publishing House of the Union of Pediatricians. All rights reserved. The lecture discusses the issue of reflux nephropathy for specialists of the system of higher medical education: the article provides the definition, characterizes the epidemiology, risk factors for disease development in children with vesicoureteral reflux, causes and molecular mechanisms of renal fibrosis formation and progression in reflux nephropathy, and markers for diagnosing and predicting the disease course. In order to control the retention of the lecture material, the text includes case problems and multiple-choice tests.
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Computed tomography in kidney injuries diagnosis
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01.01.2018 |
Barmina T.
Sharifullin F.
Abakumov M.
Zabavskaya O.
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Russian Electronic Journal of Radiology |
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© 2018 Russian Electronic Journal of Radiology. All rights reserved. Purpose. To present the possibility of the computed tomography (CT) in determination of a kidney injury for improving the quality of diagnostics and treatment of this group of patients. Materials and methods. Analyzed data comes from 72 T-researches with 50 patients with kidney injury at the closed injury of a stomach who were on treatment in Sklifosovsky Research and Clinical Institute for Emergency Medicine. Data of T was verified with the results of operations and autopsies. For determination of injury severity of a kidney the scale of Organ Injury Scale (OIS) was used. Results and discussion. Kidney injuries of the 1 degree (a contusion of a kidney and a subcapsular hematoma) were found in 12 patients, including the one with pre-existing pathology. Injuries of a kidney of the II degree were revealed in 14 patients: a cortical gap-in 9 cases, a subcapsular hematoma of a kidney with gap signs-in 3 cases; a subcapsular cyst with symptoms of hemorrhage and a gap-in two patients. Kidney injuries of the III degree were diagnosed in 7 patients in the form of a rupture of cortical substance from 12 mm to 18 mm deep. Damages of the IV degree were revealed in cases of 11 patients, including thrombosis of a segmentary branch of a renal artery in 6 patients. Injuries of a kidney of the V degree were revealed in 6 patients mainly in the form of fragmentation of a kidney. For an assessment of efficiency of treatment of 22 patients CT research in dynamics was executed, identification of complications served as the indication for repeated surgical intervention. Conclusions. T is an informative method which is possible to define not only an injury of a kidney, but also the degree of its severity. It allows to choose rational tactics for the treatment and to avoid an unreasonable nephrectomy. Performance of T in dynamics allows to estimate efficiency of treatment and in due time to diagnose complications.
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Atypical hemolytic-uremic syndrome as one of the causes of acute kidney injury in pregnant women
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01.01.2018 |
Kozlovskaya N.
Korotchaeva Y.
Shifman E.
Bobrova L.
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Terapevticheskii Arkhiv |
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© 2018 Media Sphera Publishing Group. All rights reserved. Obstetric atypical hemolytic uremic syndrome (aHUS) is one of the reasons for the development of acute kidney injury (AKI) and can determine the prognosis of both mother and child. Aim. Analysis of clinical manifestations, course and outcomes of obstetric aHUS. Materials and methods. 45 patients with aHUS development during pregnancy or immediately after childbirth were observed between 2011 and 2017, age from 16 to 42 years. Results and discussion. All patients had AKI (serum creatinine 521,5±388,0 μmol/l, oliguria or anuria that required initiation of hemodialysis). 93.3% pts had extrarenal manifestations of TMA with the development of multiple organ failure (MOF). The mean number of damage organs was 3,7±1,2. In all patients, the development of aHUS was preceded by obstetric complications, surgery, infection, etc. In the outcome: 53.4% women showed complete recovery of renal function, 11.1% developed CKD 4-5 stages, 35.5% had dialysis-dependent end-stage renal failure (ESDR). Maternal mortality was 23.9%. Perinatal mortality was 32.6%. The early start of eculizumab treatment (within 1-2 weeks from the onset of aHUS), compared with therapy start after 3 weeks, increased the chances of favorable outcome for mother in 5.33 times, and the chances for normalization of renal function in 48.7 times. Conclusion. Obstetric aHUS is characterized by the development of AKI in 100% of cases. In most patients, the obstetric aHUS occurs with the development of MOF. Timely diagnosis of aHUS and immediate treatment by eculizumab allows not only to save the life of patients, but also completely restore their health.
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