Connective tissue dysplasia as a trigger of pyelonephritis severity in children
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.
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Lavrenchuk OV. Aktual'na diagnostyka, faktory progresuvannja ta likuvannja pijelonefrytu u ditej. Diss. dokt. med. nauk [Current diagnostics, factors of progression and treatment of pyelonephritis in children. Dr. med. sci. diss.]. Kyiv: Poligraf pljus; 2015. 37p. (in Ukrainian).
Ministry of Нealth of Ukraine. Order № 627 dated November 3, 2008. On the approval of the protocol for the treatment of children with urinary tract infections and tubulointerstitial nephritis. Available from: http://old.moz.gov.ua/ua/portal/dn_20081103_627.html. Accessed: November 3, 2008. (in Ukrainian).
Frolova TV, Ohapkina OV, Sorokolat YuV, Koliushko KG. Risk of origins on the fibrillogenesis disorders in children at population. Experimental and clinical medicine. 2013;(58):131-135. (in Ukrainian).
Solejko OV, Rykalo NA, Osypenko IP, Solejko LP. Syndrom nedyferencijovanoi' dysplazii' spoluchnoi' tkanyny: vid koncepcii' patogenezu do strategii' likuvannja: navchal'nyj posibnyk [Syndrome of undifferentiated connective tissue dysplasia: from the concept of pathogenesis to the strategy of treatment: a textbook]. Vinnitsa: Nova Knyga; 2014. 166 p. (in Ukrainian).
Makarchuk OM, Rymarchuk OM, Drogomyrec'kyj LV. Undifferentiated connective tissue dysplasia as a factor of likely gestational complications. Obsterics. Gynecology. Genetics. 2015;(2);18-19. (in Ukrainian).
Zaremba EH, Rak NR. The manifestations of undifferentiated connective tissue dysplasia on the part of the cardiovascular system in patients with arterial hypertension. Acta medica Leopoliensia. 2015;21(2);14-18. (in Ukrainian).
Kazimirko VK, Ivanitskaya LM, Dubkova AG, et al. Diagnostic difficultis in undifferentiated connective tissue dysplasia in rheumalogists clinical practice. Ukrainian journal of rheumatology. 2013;(53):96-100. (in Ukrainian).
Povshedna TJu, Shevchuk DV, Kornіjchuk NM. The role of timely treatment of congenital malformations of the urinary system in preventing chronic renal insufficiency in children. Biological research. Сollection of scientific works. Zhitomir: Ruta; 2015. 423-429 pp. (in Ukrainian).
Lukyanenko NS, Kens KA, Petrіtsa NA. Evaluating the diagnostic value of the tissue hypoxia, membrane destruction and undifferentiated connective tissue dysplasia markers in young children with vesicouretheral reflux. Zdorovʹe rebenka. 2016;(74):86-92. doi: 10.22141/2224-05188.8.131.526.82138. (in Ukrainian).
Ivanov DD, Korzh OM. Nefrologija v praktyci simejnogo likarja: navchal’no-metodychnyj posibnyk [Nefrology in the practice of a family doctor: teaching aid]. Donetsk: Publisher Zaslavsky OYu; 2014. 464p.( in Ukrainian).
Podol's'kyj VV. Female reproductive health is the most important problem of our time. Zhinoche zdorov'ja. 2003;(13):100-102. (in Ukrainian).
Tempfer CB, Simoni M, Destenaves B, Fauser BC. Functional genetic polymorphisms and female reproductive disorders: part II--endometriosis. Hum Reprod Update. 2009 Jan-Feb;15(1):97-118. doi: 10.1093/humupd/dmn040.
Iur'eva EA, Dlin VV. Diagnosticheskii spravochnik nefrologa [Diagnostic guide for nephrologist]. Moscow: Overley; 2002. 95p. (in Russian).
Nyan'kovskyi SL, Dobrik OO, Іs'kiv MYu. Metabolic therapy and its role in the complex treatment of connective tissue dysplasia in Pediatric Nephrology. Sovremennaya pediatriya. 2016;(73):131-136. doi10.15574/SP.2016.73.131. (in Ukrainian).
Adi D, Xie X, Ma YT, et al. Association of COL4A1 genetic polymorphisms with coronary artery disease in Uygur population in Xinjiang, China. Lipids Health Dis. 2013 Oct 25;12:153. doi: 10.1186/1476-511X-12-153.
Kryganova TA, Dlin VV. The rate of urinary tract abnormalities and the functional state of kidneys in relation to the degree of connective tissue dysplasia in children. Rossiyskiy Vestnik Perinatologii i Pediatrii. 2016;61(3):81-86. (in Russian).
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