Skip to main content

Advertisement

SpringerLink
Log in

Primary vesicoureteral reflux; what have we learnt from the recently published randomized, controlled trials?

  • Educational Review
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

In recent years, progress has been made on understanding the relationship between vesicoureteral reflux (VUR) and urinary tract infection (UTI). The findings on recent prospective, randomized, controlled studies have questioned the conventional VUR clinical significance and, therefore, have challenged the traditional diagnostic and therapeutic recommendations. These new studies have redefined the pathogenic role of vesicoureteral reflux in UTI as well as have disputed the routine use of urinary antibiotic prophylaxis to prevent UTI and renal damage in VUR patients. The time to overinvestigate and treat the vast majority of otherwise healthy children who have an uncomplicated UTI with long-term antibiotic prophylaxis seems to be over. Is there a role of severe VUR in the development of chronic renal disease and renal failure? New ideas are needed to answer these questions with the goal to avoid repeating past mistakes when therapeutic choices were based on expert opinions rather than facts.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. National Institute of Health and Clinical Excellence (NICE)(2007). Available at: www.nice.org.uk/CG54

  2. American Academy Pediatrics Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management, Roberts KB (2011) 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 128(595–610):13

    Google Scholar 

  3. Wan J, Skoog SJ, Hulbert WC, Casale AJ, Greenfield SP, Cheng EY, Peters CA, Executive Committee, Section on Urology, American Academy of Pediatrics (2012) Section on urology response to new guidelines for the diagnosis and management of UTI. Pediatrics 129:e1051–e1053

    Article  PubMed  Google Scholar 

  4. Tekgül S, Riedmiller H, Hoebeke P, Kočvara R, Nijman RJ, Radmayr C, Stein R, Dogan HS (2012) European Association of Urology EAU guidelines on vesicoureteral reflux in children. Eur Urol 62(3):534–542

    Article  PubMed  Google Scholar 

  5. Lee T, Ellimoottil C, Marchetti KA, Banerjee T, Ivančić V, Kraft KH, Bloom DA, Park JM, Wan J (2017) Impact of clinical guidelines on voiding Cystourethrogram use and vesicoureteral reflux incidence. https://doi.org/10.1016/j.juro.2017.08.099

  6. Arant BS Jr (1991) Vesicoureteral reflux and renal injury. Am J Kidney Dis 17:491–511

    Article  Google Scholar 

  7. Bailey RR (1979) In: Hodson CJ (ed) Kincaid SmithP reflux nephropathy, 1st edn. Masson, New York, pp 59–61

    Google Scholar 

  8. Noe HN (1992) The long-term results of prospective sibling reflux screening. J Urol 148:1739–1742

    Article  CAS  PubMed  Google Scholar 

  9. Murer L, Benetti E, Artifoni L (2007) Embryology and genetics of primary vesico-ureteric reflux and associated renal dysplasia. Pediatr Nephrol 22:788–797

    Article  PubMed  Google Scholar 

  10. Baker R, Maxted W, Maylath J, Shuman I (1966) Relation of age, sex and infection to reflux: data indicating high rate of spontaneous cure rate in pediatric patients. J Urol 95:27–32

    Article  CAS  PubMed  Google Scholar 

  11. Chand DH, Rhoades SA, Kraus S, Strife CF (2003) Incidence and severity of vesicoureteral reflux in children related to age, gender, race and diagnosis. J Urol 170:1548–1550

    Article  PubMed  Google Scholar 

  12. Arant BS Jr (1992) Medical management of mild and moderate vesicoureteral reflux: follow up studies of infants and young children. A preliminary report of the Southwest Pediatric Nephrology Study group. J Urol 148:1683–1687

    Article  PubMed  Google Scholar 

  13. Tamminem-Mobius T, Brunier E, Ebel KD, Lebowitz R, Olbing H, Seppanen U, Sixt R (1992) Cessation of vesicoureteral reflux for 5 years in infants and children allocated to medical treatment. J Urol 148:1662–1666

    Article  Google Scholar 

  14. Trial Investigators RIVUR, Hoberman A, Greenfield SP, Mattoo TK, Keren R, Mathews R, Pohl HG, Kropp BP, Skoog SJ, Nelson CP, Moxey-Mims M, Chesney RW, Carpenter MA (2014) Antimicrobial prophylaxis for children with vesicoureteral reflux. N Engl J Med 370:2367–2376

    Article  CAS  Google Scholar 

  15. Pennesi M, Travan L, Peratoner L, Bordugo A, Cattaneo A, Ronfani L, Minisini S, Ventura A, North East Italy Prophylaxis in VUR study group (2008) Is antibiotic prophylaxis in children with vesicoureteral reflux effective in preventing pyelonephritis and renal scars? A randomized, controlled trial. Pediatrics 121:e1489–e1494

    Article  PubMed  Google Scholar 

  16. Schwab WC Jr, Wu H-Y, Selman H, Smith GHH, Snyder HM, Canning DA (2002) Spontaneous resolution of vesicoureteral reflux: a 15-year perspective. J Urol 168:2594–2599

    Article  PubMed  Google Scholar 

  17. Kunin CM, Deutscher R, Paquin A Jr (1964) Urinary tract infection in school children: an epidemiological, clinical, and laboratory study. Medicine 43:91–130

    CAS  PubMed  Google Scholar 

  18. Elo J, Tallgreen LG, Sarna S, Alfthan O, Stenstrom R (1981) The role of vesicoureteral reflux in pediatric urinary-tract infection. Scand J Urol Nephrol 15:243–248

    Article  CAS  PubMed  Google Scholar 

  19. Garin EH, Olavarria F, Garcia Nieto V, Valenciano B, Campos YL (2006) Clinical significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after acute pyelonephritis: a multicenter, randomized, controlled study. Pediatrics 117(626–32):9

    Google Scholar 

  20. Craig JC, Simpson JM, Williams GJ, Lowe A, Reynolds GJ, McTaggart SJ, Hodson EM, Carapetis JR, Cranswick NE, Smith G, Irwig LM, Caldwell PH, Hamilton S, Roy LP (2009) Prevention of recurrent urinary tract infection in children with Vesicoureteric reflux and normal renal tracts (PRIVENT) antibiotic prophylaxis and recurrent urinary tract infection in children. N Engl J Med 361:1748–1759

    Article  CAS  PubMed  Google Scholar 

  21. Montini G, Rigon L, Zucchetta P, Fregonese F, Toffolo A, Gobber D, Cecchin D, Pavanello L, Molinari PP, Maschio F, Zanchetta S, Cassar W, Casadio L, Crivellaro C, Fortunati P, Corsini A, Calderan A, Comacchio S, Tommasi L, Hewitt IK, Da Dalt L, Zacchello G, Dall’Amico R, IRIS Group (2008) Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized, controlled, non-inferiority trial. Pediatrics 122:1064–1071

    Article  PubMed  Google Scholar 

  22. Roussey-Kesler G, Gadjos V, Idres N, Horen B, Ichay L, Leclair MD, Raymond F, Grellier A, Hazart I, de Parscau L, Salomon R, Champion G, Leroy V, Guigonis V, Siret D, Palcoux JB, Taque S, Lemoigne A, Nguyen JM, Guyot C (2008) Antibiotic prophylaxis for the prevention of recurrent urinary tract infection in children with low grade vesicoureteral reflux: results from a prospective randomized study. J Urol 179:674–679

    Article  CAS  PubMed  Google Scholar 

  23. Brandström P, Esbjörner E, Herthelius M, Swerkersson S, Jodal U, Hansson S (2010) The Swedish reflux trial in children: III. Urinary tract infection pattern. J Urol 184:286–291

    Article  PubMed  Google Scholar 

  24. Hari P, Hari S, Sinha A, Kumar R, Kapil A, Pandey R, Bagga A (2015) Antibiotic prophylaxis in the management of vesicoureteric reflux: a randomized double-blind placebo-controlled trial. Pediatr Nephrol 30:479–486

    Article  PubMed  Google Scholar 

  25. Snodgrass WT, Shah A, Yang M, Kwon J, Villanueva C, Traylor J, Pritzker K, Nakonezny PA, Haley RW, Bush NC (2013) Prevalence and risk factors for renal scars in children with febrile UTI and/or VUR: a cross-sectional observational study of 565 consecutive patients. J Pediatr Urol 9:856–863

    Article  PubMed  Google Scholar 

  26. Hoberman A, Charron M, Hickey RW, Baskin M, Kearney DH, Wald ER (2003) Imaging studies after a first febrile urinary tract infection in young children. N Engl J Med 348:195–202

    Article  PubMed  Google Scholar 

  27. Hansson S, Jodal U, Norén L, Bjure J (1989) Untreated bacteriuria in asymptomatic girls with renal scarring. Pediatrics 84:964–968

    CAS  PubMed  Google Scholar 

  28. Bergström T, Lincoln K, Redin B, Winberg J (1968) Studies of urinary tract infections in infancy and childhood. X. Short or long-term treatment in girls with first or second-time urinary tract infections uncomplicated by obstructive urological abnormalities. Acta Paediatr Scand 57:186–194

    Article  PubMed  Google Scholar 

  29. Hewitt I, Dall’Amico R, Montini G (2014) Letter to the editor. N Engl J Med 371:1070–1073

    Article  Google Scholar 

  30. Montini G, Hewitt I (2009) Urinary tract infections: to prophylaxis or not to prophylaxis? Pediatr Nephrol 24:1605–1609

    Article  PubMed  Google Scholar 

  31. Wang HH, Gbadegesin RA, Foreman JW, Nagaraj SK, Wigfall DR, Wiener JS, Routh JC (2014) Efficacy of antibiotic prophylaxis in children with vesicoureteral reflux: systematic review and meta-analysis. J Urol 193:963–969

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hewitt IK, Pennesi M, Morello W, Ronfani L, Montini G (2017) Antibiotic prophylaxis for urinary tract infection-related renal scarring: a systematic review. Pediatrics. https://doi.org/10.1542/peds.2016-3145

  33. Wang ZT, Wehbi E, Alam Y, Khoury A (2018) A reanalysis of the RIVUR trial using a risk classification system. J Urol 199:1608–1614

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pediatric Nephrology, University of Florida, Gainesville, FL, USA

    Eduardo H. Garin

Authors
  1. Eduardo H. Garin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eduardo H. Garin.

Ethics declarations

Conflict of interest

The author has no conflict of interest to declare.

Additional information

Answers

1. c; 2. c; 3. e; 4. c; 5. c

Key summary facts

1. Non-dilating VUR does not predispose to UTI, acute pyelonephritis (APN), and renal parenchymal damage.

2. Urinary antibiotic prophylaxis is not routinely indicated in healthy children with non-dilating VUR.

3. The role of severe VUR in the pathogenesis of UTI, APN, and the use of urinary antibiotic prophylaxis needs to be defined.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Garin, E.H. Primary vesicoureteral reflux; what have we learnt from the recently published randomized, controlled trials?. Pediatr Nephrol 34, 1513–1519 (2019). https://doi.org/10.1007/s00467-018-4045-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-018-4045-9

Keywords

Search

Navigation