Markers of fibrillogenic disorders in children with different variants of pyelonephritis

Abstract

Background. In recent years, the clinical course of pyelonephritis in children is characterized by an increase in the number of latent and subclinical forms of the disease, increased resistance to traditional antibiotic therapy, which leads to chronic and recurrent pathological process in the kidneys. At the same time, the structure of nephropathy in children is characterized mainly by congenital and hereditary diseases, as well as diseases associated with hereditary predisposition, with a latent onset and torpid course. Particular attention should be paid to the children with manifestations of connective tissue dysplasia. The objective of the study: the search for possible clinical and laboratory markers associated with fibrillogenic disorders in children with different variants of pyelonephritis, and finding out the role of fibrillogenic disorders in the seve­rity of pyelonephritis in children. Materials and methods. Sixty children with pyelonephritis aged 3 to 18 years were examined. According to the results of catamnestic observation, they were divided into two groups: І — 30 children with pyelonephritis, who had 3 or more episodes of recurrent pyelonephritis du­ring the year, and ІІ — 30 children with pyelonephritis, who had no relapses during the year. The control group consisted of 42 somatically healthy children of the same age. All children underwent a routine comprehensive clinical and laboratory examination and determination of clinical and laboratory markers of fibrillogenic disorders (phenotypic signs of undifferentiated connective tissue dysplasia, hydroxyproline in urine). A molecular genetic testing of the AA and AG loci of the RS 605143 polymorphic locus of the COL4A1 gene was conducted. Results. In children with recurrent pyelonephritis, phenotypic signs of undifferentiated connective tissue dysplasia were more likely to be observed compared to those in children, who had only one episode of pyelonephritis during the year, namely: joint hypermobility (in 53 % of children versus 6.67 % in the comparison group, controls — 4.76 %), asthenic body structure (56.67 vs. 26.67 %, controls — 16.67 %), visual impairment (86.67 vs. 36.67 %, controls — 7.14 %), deformity of the chest (43.33 vs. 10 %, controls — 4.76 %), scoliostic posture (53.33 vs. 13.33 %, controls — 4.76 %), arachnodactylia and predisposition to bleeding were recorded only in children from group I (23.33 and 6.67 %, respectively, no cases in the control group). Determination of hydroxyproline level in the urine in children with recurrent pyelonephritis indicates an increased decay and excretion of collagen metabolism products in the child’s body in 97 % of the subjects, which significantly exceeds the rate of hydroxyproline urinary excretion in children with acute pyelonephritis (10 %), and indicates the significant disturbances of collagen catabolism in children prone to recurrent pyelonephritis. The probable higher frequency of the “wild” AA genotype — rs605143 gene of the collagen COL4A1 in children with recurrent pyelonephritis was found to be higher than that of the general population (21.4 vs. 4.8 %, p < 0.05). The presence of AA genotype of the rs605143 gene polymorphic locus of COL4A1 increases the risk of recurrence of chronic pyelonephritis by five times (odds ratio 5.105, 95% confidence interval 0.12–0.87). Conclusions. In order to predict a genetically determined predisposition to recurrent pyelonephritis in children, it is recommended to carry out molecular genetic testing for AA and AG genotypes of the polymorphic locus rs605143 gene of the COL4A1 collagen.