Efficacy and safety of herbal medicine in complex therapy of acute pyelonephritis in young children

Introduction. Growing antibacterial resistance of urinary tract infection pathogens in children and the risk of relapses necessitate finding the safest ways to improve treatment outcomes.

Aim. To evaluate the effectiveness of taking Canephron^® N in combination with antibacterial therapy in children aged 1 to 3 years with acute uncomplicated pyelonephritis to increase the effectiveness of therapy with a reduced risk of parenchyma damage and faster recovery of renal function.

Materials and methods. A prospective, open, randomized study was conducted in 2 groups of sick children: Group 1 (50 children) received antibacterial therapy and Canephron^® N for 10–14 days, Group 2 (50 children) – only antibacterial therapy. The duration of observation of patients was 60 days, the period of active treatment was 10–14 days, follow-up was 1.5 months. Clinical and laboratory data, partial renal functions, enzymuria (ALP, LDH, GGT), metabolic disorders were assessed.

Results and discussion. The average duration of clinical manifestations and urinary syndrome in Group 1 was 2–3 days less than in patients in Group 2. A decrease in the inflammatory process was accompanied by normalization of the functional state of the kidneys by day 15 in 85% of patients in Group 1, which was significantly better (p < 0.05) than in Group 2 (49%). In patients of Group 1, in contrast to patients of Group 2, the excretion of oxalates and calcium in urine also decreased (p < 0.05). Particular attention should be paid to the faster normalization of the level of fermenturia in patients of Group 1.

Conclusions. Combination therapy with the inclusion of a herbal preparation contributed to a faster elimination of clinical manifestations of the disease, a decrease the activity of the inflammatory process and the severity of urinary syndrome, reduced fermenturia, oxalate-calcium crystalluria and improved the processes of tubular reabsorption.

1. Breinbjerg A, Jørgensen CS, Frøkiær J, Tullus K, Kamperis K, Rittig S. Risk factors for kidney scarring and vesicoureteral reflux in 421 children after their first acute pyelonephritis, and appraisal of international guidelines. Pediatr Nephrol. 2021;36(9):2777–2787. https://doi.org/10.1007/s00467-021-05042-7.

2. Hoen LA, Bogaert G, Radmayr C, Dogan HS, Nijman RJM, Quaedackers J et al. Update of the EAU/ESPU guidelines on urinary tract infections in children. J Pediatr Urol. 2021;17(2):200–207. https://doi.org/10.1016/j.jpurol.2021.01.037.

3. Mattoo TK, Shaikh N, Nelson CP. Contemporary Management of Urinary Tract Infection in Children. Pediatrics. 2021;147(2):e2020012138. https://doi.org/10.1542/peds.2020-012138.

4. Shaikh N, Ewing AL, Bhatnagar S, Hoberman A. Risk of renal scarring in children with a first urinary tract infection: a systematic review. Pediatrics. 2010;126(6):1084–1091. https://doi.org/10.1542/peds.2010-0685.

5. Shaikh N, Craig JC, Rovers MM, Da Dalt L, Gardikis S, Hoberman A et al. Identification of children and adolescents at risk for renal scarring after a first urinary tract infection: a meta-analysis with individual patient data. JAMA Pediatr. 2014;168(10):893–900. https://doi.org/10.1001/jamapediatrics.2014.637.

6. Shaikh N, Haralam MA, Kurs-Lasky M, Hoberman A. Association of Renal Scarring With Number of Febrile Urinary Tract Infections in Children. JAMA Pediatr. 2019;173(10):949–952. https://doi.org/10.1001/jamapediatrics.2019.2504.

7. Stange R, Schneider B, Albrecht U, Mueller V, Schnitker J, Michalsen A. Results of a randomized, prospective, doubledummy, double-blind trial to compare efficacy and safety of a herbal combination containing Tropaeoli majoris herba and Armoraciae rusticanae radix with co-trimoxazole in patients with acute and uncomplicated cystitis. Res Rep Urol. 2017;9:43–50. https://doi.org/10.2147/RRU.S121203.

8. Wawrysiuk S, Naber K, Rechberger T, Miotla P. Prevention and treatment of uncomplicated lower urinary tract infections in the era of increasing antimicrobial resistance – non-antibiotic approaches: A systemic review. Arch Gynecol Obstet. 2019;300(4):821–828. https://doi.org/10.1007/s00404-019-05256-z.

9. Naber KG. Efficacy and safety of the phytotherapeutic drug Canephron® N in prevention and treatment of urogenital andgestational disease: review of clinical experience in Eastern Europe and Central Asia. Res Rep Urol. 2013;5:39–46. https://doi.org/10.2147/RRU.S39288.

10. Brenneis C, Künstle G, Haunschild J. Spasmolytic activity of Canephron N on the contractility of rat and human isolated urinary bladder. In: Proceedings of the 13th Congress of the International Society for Ethnopharmacology. Graz, Austria, 2–6 September 2012.

11. Haloui M, Louedec L, Michel JB, Lyoussi B. Experimental diuretic effects of Rosmarinus officinalis and Centaurium erythraea. J Ethnopharmacol. 2000;71(3):465–472. https://doi.org/10.1016/s0378-8741(00)00184-7.

12. Nausch B, Künstle G, Mönch B, Koeberle A, Werz O, Haunschild J. Canephron® N alleviates pain in experimental cystitis and inhibits reactive oxygen/nitrogen species as well as microsomal prostaglandin E2 synthase-1. Der Urol. 2015;54:28.

13. Künstle G, Brenneis C, Haunschild J. 671 Efficacy of Canephron® N against bacterial adhesion, inflammation and bladder hyperactivity. Eur Urol Suppl. 2013;12(1):e671. https://doi.org/10.1016/S1569-9056(13)61153-7.

14. Nausch B, Pace S, Pein H, Koeberle A, Rossi A, Künstle G, Werz O. The standardized herbal combination BNO 2103 contained in Canephron® N alleviates inflammatory pain in experimental cystitis and prostatitis. Phytomedicine. 2019;60:152987. https://doi.org/10.1016/j.phymed.2019.152987.

15. Davidov MI, Bunova NE. Comparative assessment of canephron N and ciprofloxacin as monotherapy of acute uncomplicated cystitis in women. Urologiia. 2018;(4):24–32. (In Russ.) https://doi.org/10.18565/urology.2018.4.24-32.

16. Davidov MI, Voitko DA, Bunova NE. Treatment of acute uncomplicated cystitis in women with antibiotic allergy or intolerance. Urologiia. 2019;(5):64–71. (In Russ.) https://doi.org/10.18565/urology.2019.5.64-71

17. Wagenlehner FM, Abramov-Sommariva D, Höller M, Steindl H, Naber KG. Non-Antibiotic Herbal Therapy (BNO 1045) versus Antibiotic Therapy (Fosfomycin Trometamol) for the Treatment of Acute Lower Uncomplicated Urinary Tract Infections in Women: A Double-Blind, Parallel-Group, Randomized, Multicentre, Non-Inferiority Phase III Trial. Urol Int. 2018;101(3):327–336. https://doi.org/10.1159/000493368.

18. Kirillov VI, Bogdanova NA. Clinical and pathogenetic substantiation of the effectiveness of the herbal preparation Canephron N in pediatric nephrology. RMJ. 2015;23(28):1710–1714. (In Russ.) Available at: https://www.rmj.ru/articles/pediatriya/Kliniko-patogeneticheskoe_obosnovanieeffektivnosti_rastitelynogo_preparataKanefron_N_v_nefrologii_detskogo_vozrasta/.

19. Voznesenskaya TS, Kutafina YeК. Phytotherapy treatment of urinary tract infection in children. Pediatric Pharmacology. 2007;4(5):38–40. (In Russ.) Available at: https://www.pedpharma.ru/jour/article/view/723.

20. Kirillov VI, Runenko VI, Bogdanova NA, Mstislavskaya SA. Complex therapy effect on the status of the children’s kidneys with the vesicoureteral reflux in the post operation period. Current Pediatrics. 2007;6(2):36–41. (In Russ.) Available at: https://vsp.spr-journal.ru/jour/article/view/1019.

21. Sukalo AV, Krokhina SA, Tur NI, Shevchenko OS. Use of the drug Canephron N in the complex therapy of urinary tract infections in children. Meditsinskie Novosti. 2004;(11):84–86. (In Russ.)

22. Dlin VV, Shatokhina OV, Osmanov IM, Yurieva EA. Canephron® N effectiveness in children with dysmetabolic nephropathy with oxalate-calcium cristalluria. Vestnik Pediatricheskoy Farmacologii i Nutritsiologii. 2008;5(4):66–69. (In Russ.) Available at: https://medi.ru/info/12503/