Peculiarities of Restoration of the Functional Condition of the Kidney Parenchyma in Children with Congenital Defects of the Ureterovesical Segment Depending on Methods of Its Operative Correction (According to Cytokine-enzymological Criteria)

Abstract

Congenital anomalies of the uretero-vesical junction (CAUVJ) are frequent cause of chronic kidney disease in children and if not timely corrected can lead to nephrosclerosis, hypertension and chronic renal failure. The modern arsenal of methods UVJ reconstruction includes transvesical and extravesical ureterocystoneostomy. With the transvesical approach due to trauma, the functional state of the detrusor can significantly deteriorate for a long time (up to 3 weeks), which further compromises the functions of the upper urinary tract and kidneys. In these circumstances, the scientific justification of the safest method of correction of CAUVJ is an actual problem. The advantages of determining the complex of biomarkers in the urine to assess the functional state of the kidney include high informativeness and non-invasiveness. The objective: to determine the optimal method of surgical correction of CAUVJ in children by assessing the dynamics of changes in the complex of marker cytokines: tumor growth factor beta-1 (FRP-β1), tumor necrosis factor alpha (TNF-α) and enzymes: γ-glutamyltranspeptidase (GGT) and neutral α-glucosidase (NG). Materials and methods. Children with CAUVJ (n=47) depending on the method of surgical correction were randomized into two active groups: group 1 – 23 children (transvesical technique) and group 2 – 24 children (extravesical technique). A control group of 25 healthy children was also formed, the distribution of which by age and sex corresponded to the groups from the CAUVJ. The functional status of the kidneys was assessed based on the concentration of TGF-β1, TNF-α, GGT and NG in the morning portion of urine before surgery and, respectively, 3-4 weeks, 4-6 months and 1-3 years after it. Urine was obtained during physiological urination. Concentrations of TGF-β1 and TNF-α were measured by enzyme-linked immunosorbent assay (DRG test system, USA), GGT activity – by colorimetric method (reagents of PJSC «Reagent»), NG activity – by the method of I. S. Lukomskaya. Prior to surgery, all patients were evaluated for urodynamics of the lower urinary tract. Statistical analysis: under normal distribution, the data were described as M±m, the significance of intergroup differences was assessed by Student’s t-test. The significance level was 0.05. Results. Initially, in children with CAUVJ, the average concentrations of TGF-β1, TNF-α, were significantly (p<0.001) higher than in the control group (4.6 and 6.7, respectively). The mean activity of NG and GGT was also higher in the combined group of patients with CAUVJ: 5.9 and 2.3 times, respectively, compared with the control. None of the children with CAUVJ had clinical manifestations of neurogenic bladder dysfunction. The average urodynamic parameters of the lower urinary tract in patients of groups 1 and 2 did not differ statistically (data not shown). 3-4 weeks after surgery, clinically insignificant changes in the concentration of both cytokines were registered in groups 1 and 2. In group 1, the concentration of TGF-β1 slightly (by 3 units) increased, while in group 2 – slightly (by 1 unit) decreased. The concentration of TNF-α decreased by only 3 and 5 units, respectively. The average activity of NG and GGT decreased most significantly in group 1, where extravesical methods were used: 47.4 units against 1.2 and 42 against 11.9, respectively. During this period, urinary disorders were more pronounced in group 1, where 60% of patients showed residual urine (compared to 20% in group 2), 55-60% of patients had intermittent urination, and the total effective volume of the bladder was in 2 times less than in the control group. 3-4 months after surgery, the decrease in cytokine concentration and enzyme activity in urine was also more significant in group 2 (p <0.05). Thus, the specific decrease in TGF-β1 in group 2 reached 35% vs. 26% in group 1, TNF-α – 27% vs. 17%, GGT – 62% vs. 50%, NG – 31% vs. 21%. Despite the positive dynamics, in both groups all the studied indicators remained significantly higher than those in the control group. Compared with the previous assessment, only the average level of TNF-α decreased significantly in both groups 1–3 years after the operation. Also in both groups, all indicators significantly exceeded those in the control group: TGF-β1 was 2.6 times higher (group 1) and 2.5 times (group 2), TNF-α – 3.6 times (1 group) and 3.2 times (2 groups), GGT – 2 times (1 group) and 1.8 times (2 groups), NG – 1.7 times (1 group) and 1.5 times (2 groups). At the same time, in both groups there was a complete restoration of reservoir and micturition functions of the bladder. Conclusion. CAUVJ in children is associated with a violation of the functional state of the renal parenchyma, as evidenced by a significant increase in levels of markers in the urine: TGF-β1, TNF-α, GGT and NG. Extra extravesical correction of CAUVJ in children has an advantage over transvesical, as it does not lead to transient bladder dysfunction and contributes to a more pronounced restoration of the functional state of the renal parenchyma (more pronounced decrease in levels of TGF-β1, TNF-α, GGT and NG) 1-3 months to 4-6 months after surgery. Regardless of the method of correction and even with the effective restoration of upper urinary tract function in children with CAUVJ, concentrations of markers of dysfunction of the renal parenchyma remain elevated for a long time after surgery (1-3 years), which may indicate the permanent nature of its damage. Further researches are needed to develop effective therapeutic algorithms for maintaining and restoring renal function in children with CAUVJ.