The role of nitric oxide synthase and cystatin C in the mechanisms of antimicrobial protection in children with urinary tract infections considering the etiological factor




children, urinary tract infections, cystatin C, inducible nitric oxide synthase


The aim of the study was to investigate the main etiological factors of urinary tract infections in children, the role of nitric oxide synthase and cystatin C in the mechanisms of antimicrobial protection in children with acute and chronic urinary tract infections.

Materials and methods. The study groups consisted of 84 children (mean age – 10.0 ± 1.3 years). The main group was divided into subgroups: the first subgroup – 17 children with acute pyelonephritis, the second subgroup – 21 patients with chronic pyelonephritis, the third subgroup – 16 patients with acute cystitis, the fourth subgroup – 10 patients with unspecified urinary tract infections.

The control group consisted of 20 relatively healthy children. The levels of inducible NO-synthase (NOS2) and cystatin C were measured by enzyme-linked immunosorbent assay. The etiological pathogen was identified in the urine of 200 patients with urinary tract infections.

Results. Escherichia coli was identified as the dominant pathogen in 46.7 % of cystitis patients and in 66.6 % of chronic pyelonephritis patients. The next most frequently detected etiological agent in children with acute (27.3 % of cases) and chronic (25.6 %) pyelonephritis and unspecified urinary tract infection (32.2 %) was Enterococcus faecium. Proteus mirabilis was found in 26.6 % of patients with cystitis.

The level of NOS2 in all the studied subgroups was significantly higher than that in the control group (P < 0.01). A statistically significant increase in the level of cystatin C in the main group (P < 0.05) was determined. The cystatin C-to-NOS2 ratios in the studied subgroups were 1.5–2.0 times lower than those in the control group (P < 0.05).

Conclusions. The change in the spectrum of pathogens has been determined, which was a premise of the need for constant bacteriological monitoring. The development of the primary inflammatory process in the urinary tract occurred amidst a certain dysfunction of the immune system, which was manifested in an insufficient quantitative response of cystatin C, as well as high serum levels of inducible NO-synthase in the patients.


Author Biographies

H. O. Lezhenko, Zaporizhzhia State Medical University, Ukraine

MD, PhD, DSc, Head of the Department of Hospital Pediatrics

N. A. Zakharchenko, Zaporizhzhia State Medical University, Ukraine

MD, PhD Student of the Department of Hospital Pediatrics


Balighian, E., & Burke, M. (2018). Urinary Tract Infections in Children. Pediatrics in Review, 39(1), 3-12.

Bezruk, V. V. (2015). Infektsii sechovoi systemy u ditei: etiolohichna struktura, vikovi ta henderni osoblyvosti [Urinary tract infection in children: etiological structure, age and gender characteristics]. Zdorov'e rebenka - Child`s Health, (7), 113-117. [in Ukrainian].

Budnik, T. V., & Mordovets, Ye. M. (2016). Rezultaty vyvchennia mikrobiolohichnoho portreta infektsii sechovoi systemy v ditei m. Kyieva ta Kyivskoi oblasti [The results of the study of microbiologic pattern of the urinary tract infection in children from Kyiv and Kyiv region]. Pochky - Kidneys, (2), 21-25. [in Ukrainian].

Eremenko, R., Barmatz, S., Lumelsky, N., Colodner, R., Strauss, M., & Alkan, Y. (2020). Urinary Tract Infection in Outpatient Children and Adolescents: Risk Analysis of Antimicrobial Resistance. The Israel Medical Association journal : IMAJ, 22(4), 236-240.

't Hoen, L. A., Bogaert, G., Radmayr, C., Dogan, H. S., Nijman, R., Quaedackers, J., Rawashdeh, Y. F., Silay, M. S., Tekgul, S., Bhatt, N. R., & Stein, R. (2021). Update of the EAU/ESPU guidelines on urinary tract infections in children. Journal of pediatric urology, 17(2), 200-207.

Khan, A., Jhaveri, R., Seed, P. C., & Arshad, M. (2019). Update on Associated Risk Factors, Diagnosis, and Management of Recurrent Urinary Tract Infections in Children. Journal of the Pediatric Infectious Diseases Society, 8(2), 152-159.

Korbel, L., Howell, M., & Spencer, J. D. (2017). The clinical diagnosis and management of urinary tract infections in children and adolescents. Paediatrics and international child health, 37(4), 273-279.

Lameire, N., Van Biesen, W., & Vanholder, R. (2017). Epidemiology of acute kidney injury in children worldwide, including developing countries. Pediatric nephrology (Berlin, Germany), 32(8), 1301-1314.

Lee, M., Rey, K., Besler, K., Wang, C., & Choy, J. (2017). Immunobiology of Nitric Oxide and Regulation of Inducible Nitric Oxide Synthase. Results and problems in cell differentiation, 62, 181-207.

Leung, A. K. C., Wong, A. H. C., Leung A. A. M., & Hon, K. L. (2019). Urinary Tract Infection in Children. Recent Patents on Inflammation & Allergy Drug Discovery, 13(1), 2-18.

Lezhenko, G. O., Pashkova, O. Ye., Rudova, O. I., & Rubanova, Ye. I. (2014). Dosvid zastosuvannia tsefiksymu v likuvanni infektsii sechovoi systemy u ditei. [Experience of Cefixime application for the treatment of urinary tract infection in children]. Zdorov'e rebenka - Child`s, (3), 12-16. [in Ukrainian].

Logadottir, Y., Hallsberg, L., Fall, M., Peeker, R., & Delbro, D. (2013). Bladder pain syndrome/interstitial cystitis ESSIC type 3C: high expression of inducible nitric oxide synthase in inflammatory cells. Scandinavian journal of urology, 47(1), 52-56.

Magister, S., & Kos, J. (2013). Cystatins in immune system. Journal of Cancer, 4(1), 45-56.

Millner, R., & Becknell, B. (2019). Urinary tract infections. Pediatric Clinics of North America. 66(1), 1-13.

Sadeghi-Bojd, S., Naghshizadian, R., Mazaheri, M., Ghane Sharbaf, F., & Assadi, F. (2020). Efficacy of Probiotic Prophylaxis After The First Febrile Urinary Tract Infection in Children With Normal Urinary Tracts. Journal of the Pediatric Infectious Diseases Society, 9(3), 305-310.

Svensson, L., Poljakovic, M., Demirel, I., Sahlberg, C., & Persson, K. (2018). Host-Derived Nitric Oxide and Its Antibacterial Effects in the Urinary Tract. Advances in microbial physiology, 73, 1-62.

Vumma, R., Bang, C. S., Kruse, R., Johansson, K., & Persson, K. (2016). Antibacterial effects of nitric oxide on uropathogenic Escherichia coli during bladder epithelial cell colonization--a comparison with nitrofurantoin. The Journal of antibiotics, 69(3), 183-186.

Watson, J. R., Sánchez, P. J., Spencer, J. D., Cohen, D. M., & Hains, D. S. (2018). Urinary Tract Infection and Antimicrobial Stewardship in the Emergency Department. Pediatric emergency care, 34(2), 93-95.

Xu, Y., Ding, Y., Li, X., & Wu, X. (2015). Cystatin C is a disease-associated protein subject to multiple regulation. Immunology and cell biology, 93(5), 442-451.

Ministry of Health of Ukraine. (2008, November 3). Pro zatverdzhennia protokolu likuvannia ditei z infektsiiamy sechovoi systemy i tubolointerstytsialnym nefrytom [On the approval of the treatment protocol for children with urinary system infections and tubulointerstitial nephritis (No. 627)].

Zi, M., & Xu, Y. (2018). Involvement of cystatin C in immunity and apoptosis. Immunology letters, 196, 80-90.




How to Cite

Lezhenko HO, Zakharchenko NA. The role of nitric oxide synthase and cystatin C in the mechanisms of antimicrobial protection in children with urinary tract infections considering the etiological factor. Zaporozhye Medical Journal [Internet]. 2022Aug.1 [cited 2024Jun.18];24(4):459-63. Available from:



Original research