Objective of the study: to study the clinical significance of the determination of angiotensin 2 (Ang II) and transforming growth factor β1 (TGF-β1) in urine of children with acute and chronic secondary pyelonephritis (PN) for increasing the efficiency of diagnosis of the disease. Materials and methods of research: a prospective open non-randomized controlled longitudinal single-center study was carried out in the Speransky City Children’s Hospital № 9 from January 10, 2015 to June 2020 to study the sensitivity and specificity of the tests under study. 60 children from 1 to 15 years old with acute and chronic secondary PN were examined. Children were divided into 2 groups: 1st – 30 patients with the onset of acute PN, 2nd – 30 patients with recurrent chronic secondary PN. The control group consisted of 20 apparently healthy children. In the 1st group of patients, girls predominated (24 children, 80%), the median age was 7 [3; 9] years, the median duration of followup is 41 [8; 45] months from the onset of the disease. In the 2nd group girls also predominated – 23 (77%), the median age – 8 [5; 11] years, the median duration of the disease at the time of inclusion in the study was 5 [3; 9] years. Most children were diagnosed with vesicoureteral reflux (VUR): grade I–II – in 18 (60%) and grade II–III – in 7 (23%). Incomplete renal doubling was detected in 4 (14%) patients, complete – in one (3%). The control group mainly consisted of girls – 16 (80%), the median age – 5,5 [3,25; 8,75] years. All patients underwent a study of general clinical and biochemical blood test, general analysis of urine, determination in a single morning portion of urine by enzyme immunoassay method according to ELISA TGF-β1 and Ang II. To standardize the level of TGF-β1 and Ang II in the urine, the level of creatinine in each portion of urine was determined and the results were converted to 1 mg of creatinine. Instrumental examination included ultrasound of the kidneys and bladder before and after micturition. Static nephroscintigraphy was performed 6 months after the onset of the disease or recurrence of chronic secondary PN. Results: it was found that at the onset of acute PN and with relapses of chronic secondary PN, there was an increased urinary excretion of TGF-β1 (p=0,002) and Ang II (p=0,002) when compared with the control group. It was shown that the level of increase in these markers depended on the form of PN. There were statistically significant differences in the urinary excretion of TGF-β1 and Ang II in children with acute PN and exacerbation of chronic secondary PN prior to the initiation of antibiotic therapy (p=0,001 and p=0,001, respectively). Urinary levels of Ang II and TGF-β1 in patients with exacerbation of chronic secondary PN in the first days of the microbial-inflammatory process in the renal parenchyma were by an order of magnitude higher than those in children with the onset of acute PN. A high degree of correlation was revealed between the level of uAng II/Cr and uTGF-β1/Cr (r=0,75, p=0,0001 and r=0,89, p=0,0001, respectively) in the 1st and 2nd groups of children (r=0,86, p=0,0001 and r=0,75, p=0,001, respectively) in the acute phase of the disease before antibiotic therapy with the data obtained during static nephroscintigraphy in the period of remission of the disease. Conclusion: the results indicate the importance of studying the urinary excretion of Ang II/Cr and TGF-β1/Cr as additional diagnostic markers for the identification of patients with a relapse current of PN, as well as to predict the degree of development of sclerotic processes in the renal tissue in children with different forms of PN.
Angiotensin stimulates TGF-β1 and clusterin in the hydronephrotic neonatal rat kidney
