Evolving Approaches to Pediatric Vesicoureteral Reflux: Diagnostic Innovations, Risk Stratification, and Treatment Trends
Main Article Content
Abstract
Vesicoureteral reflux (VUR) is a common pediatric condition historically managed with a goal of preventing renal injury from recurrent urinary tract infections (UTIs). However, contemporary understanding recognizes that not all reflux confers the same risk. This review highlights evolving diagnostic strategies, risk stratification tools, and treatment trends in VUR management. The natural history of VUR is influenced by multiple factors, including grade, timing on voiding cystourethrogram (VCUG) presence of bladder and bowel dysfunction (BBD), and anatomical anomalies. While many cases of low-grade reflux resolve spontaneously, high-grade or early-filling VUR, especially with BBD, poses a higher risk of persistent disease and recurrent febrile UTIs.Diagnosis has shifted toward minimizing invasive testing and radiation exposure. Contrast-enhanced voiding urosonography (ceVUS) offers a non-radiating alternative to VCUG with excellent diagnostic accuracy. Adjunctive tools such as the ureteral diameter ratio (UDR) and Vesicoureteral Reflux Index (VURx) enhance risk stratification and predict likelihood of resolution or breakthrough infections. Treatment has similarly evolved. Observation and selective use of continuous antibiotic prophylaxis (CAP) are now standard for low-risk patients, reflecting concerns about resistance and microbiome disruption. Endoscopic injection using the Double HIT method provides high success rates with minimal morbidity and is now widely favored over open surgery in most cases. Robotic ureteral reimplantation is increasingly utilized, though its cost and learning curve remain barriers to widespread adoption. Emerging research in artificial intelligence, urinary biomarkers, and microbiome preservation offers promise for even more personalized care. Revised guidelines and multicenter registries are fostering data-driven, risk-based approaches. VUR management has transitioned from a uniform treatment model to a nuanced, individualized strategy. Innovations in diagnostics, quantitative risk tools, and minimally invasive therapies now support safe, effective, and tailored care. The focus continues to shift toward optimizing long-term outcomes while reducing treatment burden for children with VUR.
Keywords:
Vesico-Ureteral Reflux, Pediatrics, Risk Assessment, Diagnostic Imaging, Ultrasonography, Anti-Bacterial Agents, Endoscopic Surgery, Robotic Surgical Procedures, Bladder and Bowel Dysfunction, Ureteral Diameter Ratio, Artificial Intelligence, Microbiome, Urinary Tract Infections
Article Details
How to Cite
PRESS, Benjamin; GERMANY, Rachael; KIRSCH, Andrew.
Evolving Approaches to Pediatric Vesicoureteral Reflux: Diagnostic Innovations, Risk Stratification, and Treatment Trends.
Medical Research Archives, [S.l.], v. 13, n. 7, july 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6718>. Date accessed: 07 dec. 2025.
doi: https://doi.org/10.18103/mra.v13i7.6718.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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2. Läckgren G. Management of Vesicoureteral Reflux: What Have We Learned Over the Last 20 Years? Frontiers in Pediatrics. 2021;9:650326.
3. Mattoo TK. Vesicoureteral Reflux and Reflux Nephropathy. Advances in Chronic Kidney Disease. 2011;18(5):348-54.
4. Elder JS, Diaz M. Vesicoureteral Reflux—Traditional Concepts and New Insights. Nature Reviews Urology. 2013;10(11):640-8.
5. Kirsch AJ, Arlen AM. The Ureteral Diameter Ratio as a Predictor of VUR Resolution. Journal of Pediatric Urology. 2014;10(6):1249-54.
6. Arlen AM, Kirsch AJ. Contemporary Outcomes of VUR Management in the United States. The Journal of Urology. 2020;204(3):572-7.
7. Chua ME. Diagnostic Accuracy of CeVUS Versus VCUG: A Meta-Analysis. World Journal of Urology. 2019;37(11):2245-55.
8. Ntoulia A. Contrast-Enhanced Voiding Urosonography: A Radiation-Free Option. Pediatric Radiology. 2018;48(2):216-26.
9. Investigators RT. Antimicrobial Prophylaxis for Children with Vesicoureteral Reflux. New England Journal of Medicine. 2014;370:2367-76.
10. Langley JM. Antibiotic Prophylaxis in Children: Resistance and Microbiome Impacts. Journal of the Pediatric Infectious Diseases Society. 2023;12(1):15-24.
11. Williams G. Antibiotics for Preventing Recurrent UTI in Children. Cochrane Database of Systematic Reviews. 2019(2):CD001532.
12. Kirsch AJ, Arlen AM. Evolving surgical management of pediatric vesicoureteral reflux: is open ureteral reimplantation still the 'Gold Standard'? International braz j urol : official journal of the Brazilian Society of Urology. 2020;46(3):314-21.
13. Peters CA. Robotic Ureteral Reimplantation: Contemporary Outcomes. The Journal of Urology. 2023;209(2):401-8.
14. Sorensen MD. Cost-Effectiveness and Complications of Bilateral Robotic Reimplantation. Urology. 2024; 175:67-73.
15. Sargent MA. What is the normal prevalence of vesicoureteric reflux? Pediatric Radiology. 2000; 30(9):587-93.
16. Noe HN. The long-term results of prospective sibling reflux screening. Journal of Urology. 1992; 148:1739-42.
17. van Eerde AM, Duran K, van Riel E, de Kovel CGF, Koeleman BPC, Knoers NVAM, et al. Genes in the Ureteric Budding Pathway: Association Study on Vesico-Ureteral Reflux Patients. PLOS ONE. 2012;7(4):e31327.
18. Westland R, Renkema KY, Knoers NVAM. Clinical Integration of Genome Diagnostics for Congenital Anomalies of the Kidney and Urinary Tract. Clinical Journal of the American Society of Nephrology. 2021;16(1):128-37.
19. Peters CA, Skoog SJ, Arant BS, et al. Summary of the AUA guideline on management of primary vesicoureteral reflux in children. Journal of Urology. 2010;184:1134-44.
20. Kirsch AJ, Arlen AM, Leong T, Merriman LS, Herrel LA, Scherz HC, et al. Vesicoureteral reflux index (VURx): a novel tool to predict primary reflux improvement and resolution in children less than 2 years of age. J Pediatr Urol. 2014;10(6):1249-54.
21. Cooper CS. Diagnosis and management of vesicoureteral reflux. Pediatrics in Review. 2017; 38(11):505-17.
22. Elder JS. Imaging for vesicoureteral reflux: bottom-up, top-down or none of the above. J Urol. 2006;176(3):1063-9.
23. Peters CA, Skoog SJ, Arant BS, et al. Summary of the AUA guideline on management of primary vesicoureteral reflux in children. J Urol. 2010; 184:1134-44.
24. Çelebi S, Özaydın S, Baştaş CB, Kuzdan Ö, Erdoğan C, Yazıcı M, et al. Reliability of the Grading System for Voiding Cystourethrograms in the Management of Vesicoureteral Reflux: An Interrater Comparison. Advances in urology. 2016;2016:1684190.
25. Metcalfe CB, Macneily AE, Afshar K. Reliability assessment of international grading system for vesicoureteral reflux. J Urol. 2012;188(4 Suppl):1490-2.
26. Ozaydin S, Celebi S, Caymaz I, Besik C, Karaaslan B, Kuzdan O, et al. Increasing the Reliability of the Grading System for Voiding Cystourethrograms Using Ultrasonography: An Inter-Rater Comparison. Nephro-urology monthly. 2016;8(5):e38685.
27. Frimberger D, Bauer SB, Cain MP, Greenfield SP, Kirsch AJ, Ramji F, et al. Establishing a standard protocol for the voiding cystourethrography. J Pediatr Urol. 2016;12(6):362-6.
28. Janssen KM, Kirsch AJ, Crisostomo-Wynne TC, Leong T, Cuda SP, Arlen AM. Standardized protocol for voiding cystourethrogram: Are recommendations being followed? J Pediatr Urol. 2021;17(1):66.e1-.e6.
29. Polito C, Moggio G, La Manna A, Cioce F, Cappabianca S, Di Toro R. Cyclic voiding cystourethrography in the diagnosis of occult vesicoureteric reflux. Pediatric nephrology (Berlin, Germany). 2000;14(1):39-41.
30. Subcommittee on Urinary Tract Infection RKB. Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics. 2011;128(3):595-610.
31. Chua ME, Ming JM. Diagnostic accuracy of contrast-enhanced voiding urosonography compared with voiding cystourethrography in children: a meta-analysis. World J Urol. 2019; 37(11):2245-55.
32. Kirsch AJ, Arlen AM. Utility of the ureteral diameter ratio and bladder volume in predicting vesicoureteral reflux resolution. J Urol. 2014; 192(1):194-9.
33. Ntoulia A. Contrast-enhanced voiding urosonography: a radiation-free alternative for diagnosing vesicoureteral reflux. Pediatr Radiol. 2018;48(2):216-26.
34. Arlen AM, Kirsch AJ, Leong T, Cooper CS. Validation of the ureteral diameter ratio for predicting early spontaneous resolution of primary vesicoureteral reflux. Journal of Pediatric Urology. 2017;13(4):383.e1-.e6.
35. Arlen AM, Leong T, Guidos PJ, Alexander SE, Cooper CS. Distal ureteral diameter ratio is predictive of breakthrough febrile urinary tract infection. Journal of Urology. 2017;198(6):1418-23.
36. Cooper CS, Alexander SE, Kieran K, Storm DW. Utility of the distal ureteral diameter on VCUG for grading VUR. Journal of Pediatric Urology. 2015;11(4):183.e1-.e6.
37. Cooper CS, Birusingh KK, Austin JC, Knudson MJ, Brophy PD. Distal ureteral diameter measurement objectively predicts vesicoureteral reflux outcome. Journal of Pediatric Urology. 2013;9(1):99-103.
38. Swanton AR, Arlen AM, Alexander SE, Kieran K, Storm DW, Cooper CS. Inter-rater reliability of distal ureteral diameter ratio compared to grade of VUR. J Pediatr Urol. 2017;13(2):207.e1-.e5.
39. Arlen AM, Garcia-Roig M, Weiss AD, Leong T, Cooper CS, Kirsch AJ. Vesicoureteral Reflux Index: 2-Institution Analysis and Validation. J Urol. 2016; 195(4 Pt 2):1294-9.
40. Garcia-Roig M, Ridley DE, McCracken C, Arlen AM, Cooper CS, Kirsch AJ. Vesicoureteral Reflux Index: Predicting Primary Vesicoureteral Reflux Resolution in Children Diagnosed after Age 24 Months. J Urol. 2017;197(4):1150-7.
41. Arlen AM, Leong T, Wu CQ, Traore EJ, Cooper CS, Kirsch AJ. Predicting Breakthrough Urinary Tract Infection: Comparative Analysis of Vesicoureteral Reflux Index, Reflux Grade and Ureteral Diameter Ratio. J Urol. 2020;204(3):572-7.
42. Hoberman A, Greenfield SP, Mattoo TK. Imaging studies after a first febrile urinary tract infection in young children. N Engl J Med. 2003; 348(3):195-202.
43. Khondker A, Kwong JC, Malik S, Erdman L, Keefe DT, Fernandez N, et al. The state of artificial intelligence in pediatric urology. Frontiers in Urology. 2022;Volume 2 - 2022.
44. American Urological A. VUR clinical practice guideline. 2023.
45. Skoog SJ. Pediatric vesicoureteral reflux guidelines: an update. Journal of Urology. 2010; 184(3):1134-44.
46. G W, JC C. Antibiotics for preventing recurrent urinary tract infection in children. Cochrane Database Syst Rev. 2019(2):CD001532.
47. JM L. Antibiotic prophylaxis in children: resistance and microbiome impacts. J Pediatric Infect Dis Soc. 2023;12(1):15–24.
48. M G-R, AJ K. The role of antibiotic prophylaxis in the management of vesicoureteral reflux. J Urol. 2018;199(1):287–93.
49. TK M. Vesicoureteral reflux and reflux nephropathy. Adv Chronic Kidney Dis. 2011;18(5):348–54.
50. Fouhy F. The effect of antibiotics on the infant gut microbiome. Gut Microbes. 2021;13(1):1939834.
51. Mattoo TK. Contemporary management of vesicoureteral reflux. Pediatric Nephrology. 2022; 37:1501-10.
52. Peters CA, Skoog SJ, Arant BS, Jr., Copp HL, Elder JS, Hudson RG, et al. Summary of the AUA Guideline on Management of Primary Vesicoureteral Reflux in Children. The Journal of urology. 2010; 184(3):1134-44.
53. Kirsch AJ, Cooper CS, Läckgren G. Non-Animal Stabilized Hyaluronic Acid/Dextranomer Gel (NASHA/Dx, Deflux) for Endoscopic Treatment of Vesicoureteral Reflux: What Have We Learned Over the Last 20 Years? Urology. 2021;157:15-28.
54. Garcia-Roig M, Travers C, McCracken CE, Kirsch AJ. National Trends in the Management of Primary Vesicoureteral Reflux in Children. The Journal of urology. 2018;199(1):287-93.
55. Routh JC, Inman BA, Reinberg Y. Dextranomer /hyaluronic acid for pediatric vesicoureteral reflux: systematic review. Pediatrics. 2010;125(5):1010-9.
56. Yap T-L, Chen Y, Nah SA, Ong CCP, Jacobsen A, Low Y. STING versus HIT technique of endoscopic treatment for vesicoureteral reflux: A systematic review and meta-analysis. Journal of Pediatric Surgery. 2016;51(12):2015-20.
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