Connective tissue dysplasia as a trigger of pyelonephritis severity in children

N.S. Lukyanenko, M.Yu. Iskiv, K.A. Kens, H.V. Makuch


Background. In recent decades, more and more attention of practitioners is attracted to the role of pathology of various organs and systems of the human body associated with connective tissue dysplasia, which leads to chronicity and relapse of the pathological process in the kidneys. The purpose of the research: to clarify the role of undifferentiated connective tissue disease in the severity of pyelonephritis in children and to search for possible molecular genetic markers associated with violations of fibrillogenesis in children with different clinical course of pyelonephritis. Materials and methods. There were examined 60 children with pyelonephritis aged 3–18 years. According to the results of follow-up, they were divided in 2 groups: І — 30 patients with chronic pyelonephritis, whose follow-up was characterized by 3 and more pyelonephritis relapses during 2 years, ІІ — 30 children with pyelonephritis, who didn’t have relapses within 2 years. The control group consisted of 42 somatically healthy children of the same age. All children underwent the routine comprehensive clinical and laboratory examination, clinical and laboratory markers of fibrillogenesis disorders were evaluated. There was conducted the molecular and genetic investigation of polymorphic locі rs605143 of collagen gene COL4A1 and rs565470 of collagen gene COL4A2. Results. In children with chronic pyelonephritis, phenotypic signs of undifferentiated connective tissue dysplasia were significantly more common as compared to that of children, who had only one episode of pyelonephritis a year. Virtually in all examined children with chronic pyelonephritis, the values of free and bound fractions of hydroxyproline in the blood plasma were significantly increased (47.14 ± 0.03 μmol/l and 40.08 ± 0.03 μmol/l, respectively) indicating an increased collagen exchange, and differed reliably from those in patients with acute pyelonephritis (17.65 ± 0.01 μmol/l and 17.22 ± 0.02 μmol/l), whose hydroxyproline fractions were elevated only by 12.0 and 16.0 %, respectively. In 97.0 % of children with chronic pyelonephritis, elevated levels of urinary hydroxyproline were detected indicating an increase in the breakdown and excretion of collagen metabolism products, which significantly exceeds the rate of excretion of hydroxyproline in patients with acute pyelonephritis (10 %). The frequency of the wild AA genotype rs605143 of the COL4A1 collagen gene in children with recurrent chronic pyelonephritis was found to be higher than that of control group (21.4 vs. 4.8 %, p < 0.05). The presence in a child of AA genotype of the polymorphic rs605143 locus of the COL4A1 collagen gene five times increases the risk of chronic pyelonephritis recurrence (odds ratio (OR) 5.105, 95% confidence interval (CI) 0.12–0.87). On the contrary, as our studies have shown, the presence of TT genotype of the polymorphic locus rs565470 of the COL4A2 collagen gene reduces the risk of pyelonephritis recurrence (OR 0.14, 95% CI 0.02–1.19). Conclusions. The presence of undifferentiated connective tissue dysplasia in a child plays an important role in the course of chronic pyelonephritis. In order to predict genetically determined propensity to pyelonephritis relapse, it is recommended to carry out a molecular genetic testing of AA and AG genotypes of the polymorphic locus rs605143 of COL4A1 collagen gene, and TT and TS the genotypes of the rs565470 polymorphic locus of the COL4A2 collagen gene.


children; connective tissue dysplasia; violations of fibrillogenesis; clinical laboratory and molecular genetic markers of dysplasia; hydroxyproline; collagen; pyelonephritis


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