Cytokine Profile and Enzymes of Tubular Nephrothelium in the Urine of Children with Congenital Megaureter
Authors: Nikulina Halyna , Myhal Liudmyla , Petersburgsky Volodymyr , Drannik Heorhii , Kalinina Nataliia , Kalischuk Oles , Serbina Iryna , Savchenko Viktoriia 
Published: October 2023

The objective: to determine the concentration of transforming growth factor β1 (TGF-β1), interleukin 1β (IL-1β) and tumor necrosis factor-α (TNF-α), activity levels of tubular nephrothelium enzymes total N-acetyl-β-D-glucosaminidase (NAG), its thermostable NAG isoenzyme B (NAG-B), β-galactosidase (β-Gal), γ-glutamyl transpeptidase (GGT) and neutral α-glucosidase (Nα-Gl) as cytokine-enzymological risk criteria for the development of nephrofibrosis in the urine of children with congenital nonrefluxing megaureter (NRMU) and refluxing megaureter (RMU) with unilateral and bilateral localization of the pathological process.
Materials and methods. 174 patients with congenital MU were examined, who were divided into two groups. Group 1 included 131 children with NRMU, group 2 – 43 children with RMU aged from 6 months to 15 years. The control group included 25 practically healthy children.
There were 97 patients with unilateral NRMU (group 1a), with bilateral – 34 persons (group 1b); there were 16 patients with unilateral RMU (group 2a), with bilateral – 27 (group 2b). Cytokine and enzyme indicators were studied in the morning portion of urine before reconstructive treatment. The levels of cytokines were determined by the ELISA method. Enzyme activity of urine was determined by the colorimetric method.
Statistical processing of data was performed after analyzing the conformity of their distribution to the norm parameters.
Results. It was found that the levels of TGF-β1, IL-1β and TNF-α, as well as the activity levels of NAG, NAG-B, β-Gal, GGT and Nα-Gl in the urine of patients with both congenital NRMU and congenital RMU are significantly increased compared to similar indicators in the control group (p<0.001). In patients with congenital RMU, compared to similar average indicators of patients with congenital NRMU, there is a significant increase of all cytokine and enzyme parameters (р<0.05–0.001), which indicates the probability of ischemic-hypoxic, as well as fibrotic damages in the kidney parenchyma in children with MU, especially in patients with RMU.
A significant increase in the cytokine levels and enzyme activity levels were established in patients with NRMU and RMU with a unilateral process compared to similar control data (p<0.001. A statistically significant increase of TNF-α, the activity of NAG-B and β-Gal in patients with bilateral NRMU, the concentration of IL-1β, TNF-α and activity levels of NAG, NAG-B, β-Gal, GGT and Nα-Gl in patients with bilateral RMU compared with similar data in groups of patients with unilateral process was found (p<0.05–0.001).
Conclusions. Congenital MU (NRMU, RMU) negatively affects the function of the tubular nephrothelium, which is manifested by an increased level of profibrogenic cytokine TGF-β1 and pro-inflammatory cytokines IL-1β and TNF-α in the urine of children, as well as the activity levels of lysosomal enzymes NAG, NAG-B, β-Gal and brush border enzymes GGT and Nα-Gl, which have renal specific properties. This indicates a high probability of ischemic processes in the kidney parenchyma and the risk of nephrofibrosis development in these patients, especially in patients with RMU with bilateral localization of the pathological process.