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The Diagnosis and Medical Management of Vesicoureteral Reflux: An Update and Current Controversies

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Pediatric Surgery
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Abstract

Primary vesicoureteral reflux (VUR) is most often diagnosed in children after a urinary tract infection (UTI), in infants with a prenatal ultrasound showing hydronephrosis, or in asymptomatic siblings of probands with VUR. While other diagnostic modalities have been advocated, the voiding cystourethrogram (VCUG) remains the most accurate. In particular, renal ultrasound (USG) will miss many children with all grades of reflux. Renal scarring, either due to renal dysplasia at birth or after pyelonephritis, is the most consequential of the sequelae of undiagnosed and untreated VUR. Recurrent urinary infection without pyelonephritic scarring, while of less significance, also contributes to VUR-related morbidity. Long-term, continuous low-dose antibiotic prophylaxis has been the mainstay of medical management. The majority of those with low-grade VUR (grades I, II, and III) outgrow their reflux with somatic growth, and they constitute 90% of all children identified with VUR. Continuous prophylaxis has been shown to prevent recurrent UTIs during the years of observation. More recently, the rationale for continuous prophylaxis has been challenged. Conflicting studies have produced contradictory outcomes, arguing for and against the benefit of prophylaxis. These studies and their shortcomings are discussed at length. Most recently, the results of the NIH-sponsored RIVUR (Randomized Intervention for children with Vesicoureteral Reflux) Trial were published, showing that continuous prophylaxis halved the number of UTIs over a 2-year observation period. Renal scarring was not decreased, however. The presence of bowel and bladder dysfunction (BBD) was a significant contributing factor to recurrent UTI. While it is known that many children might not require medical management, it is not possible to segregate those at risk for recurrent UTI, with or without renal involvement. The identification of those at greatest risk who would benefit from treatment remains a challenge for future research.

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References

  • Abdelhalim A, Khoury AE. Critical appraisal of the top-down approach for vesicoureteral reflux. Investig Clin Urol. 2017;58(Suppl 1):S14–22.

    Google Scholar 

  • Arlen AM, Kirsch AJ, Leong T, Cooper CS. Validation of the ureteral diameter ratio for predicting early spontaneous resolution of primary vesicoureteral reflux. J Pediatr Urol 2017;13:383.e1.

    Google Scholar 

  • Arthurs OJ, Edwards AD, et al. Intractive magnetic resonance voiding cystourethrography (iMRVC) for vesicoureteric reflux (VUR) in unsedated infants: a feasibility study. Eur Radiol. 2011;21:1874–81.

    Google Scholar 

  • Bayrum MT, Kavukcu S, et al. Place of ultrasonography in predicting vesicoureteral reflux in patients with mild renal scarring. Urol. 2014;83:904–8.

    Google Scholar 

  • Benninga M, Candy DC, et al. The Paris consensus on childhood constipation terminology (PACCT) group. J Pediatr Gastroeneterol Nutr. 2005;40:273–5.

    Google Scholar 

  • Boubnova J, Sergent-Alaoui A, et al. Evolution and prognosis value of intrarenal reflux. J Ped Urol. 2010;7:638–43.

    Google Scholar 

  • Brandstom P, Neveus T, et al. The Swedish reflux trial in childreh: IV. Renal Damage. J Urol. 2010;184:292–7.

    Google Scholar 

  • Brandstrom P, Esbjorner E, et al. The Swedish reflux trial in children: III. Urinary tract infection pattern. J Urol. 2010;184:286–91.

    Google Scholar 

  • Bulut IK, Mir S, et al. The predictive value of urinary UPIb mRNA levels in VUR and recurrent urinary tract infections. Clin Nephrol. 2014;81:152–8.

    Google Scholar 

  • Cannon GM, Arahna AA, et al. Improvement in vesicoureteral reflux grade on serial imaging predicts resolution. J Urol. 2010;183:709–13.

    Google Scholar 

  • Carpenter MA, Hoberman A, et al. The RIVUR trial: profile and baseline clinical associations of children with vesicoureteral reflux. Pediatrics. 2013;132:e34–45.

    Google Scholar 

  • Cascio S, Colhoun E, Puri P. Bacterial colonization of the prepuce in boys with vesicoureteral reflux who receive antibiotic prophylaxis. J Peds. 2000;139:160–2.

    Google Scholar 

  • Cheng CH, Hang JF, et al. Nephromegaly is a significant risk factor for renal scarring in children with first febrile urinary tract infections. J Urol. 2011;186:2353–5849.

    Google Scholar 

  • Cooper CS, Birusingh KK, Austin JC, et al. Distal ureteral diameter measurement objectively predicts vesicoureteral reflux outcome. J Pediatr Urol 2013;9:99.

    Google Scholar 

  • Cooper CS, Alexander SE, Kieran K, Storm DW. Utility of the distal ureteral diameter on VCUG for grading VUR. J Pediatr Urol 2015;11:183.e1.

    Google Scholar 

  • Craig J, Simpson JM, et al. Antibiotic prophylaxis and recurrent urinary tract infection. NEJM. 2009;361:1748–59.

    Google Scholar 

  • D’Souza MK, Verma NS, et al. Detecting reflux: does ureteric jet doppler waveform have a role? Pediatr Nephro. 2013;28:1821–6.

    Google Scholar 

  • Darlow JM, Darlay R, Dobson MG, Stewart A, Charoen P, Southgate J, Baker SC, Xu Y, Hunziker M, Lambert HJ, Green AJ, Santibanez-Koref M, Sayer JA, Goodship THJ, Puri P, Woolf AS, Kenda RB, Barton DE, Cordell H. Genome-wide linkage and association study implicates the 10q26 region as a major genetic contributor to primary nonsyndromic vesicoureteric reflux. J Sci Rep. 2017;7(1):14595.

    Google Scholar 

  • Drube J, Schiffer E, et al. Urinary proteome analysis to exclude severe vesicoureteral reflux. Pediatrics. 2012;129:e356–63.

    Google Scholar 

  • Duran C, del Riego J, Riera L, et al. Voiding urosonography including urethrosonography: high-quality examinations with an optimised procedure using a second-generation US contrast agent. Pediatr Radiol. 2012;42:660–7.

    Google Scholar 

  • Elder JS, Longnecker R. Premedication with oral midazolam for voiding cystourethrogram in children: safety and efficacy. Am J Rad. 1995;164:1229–32.

    Google Scholar 

  • Fallah MM, Falahati M, et al. Comparative study of color doppler voiding urosonagraphy without contrast enhancement and direct radionuclide voiding cystography for diagnosis of vesicoureteric reflux in children. J Ultrasound Med. 2012;31:55–61.

    Google Scholar 

  • Farhat W, Bagli DJ, et al. The dysfunctional voiding scoring system: quantitative standardization of dysfunctional voiding symptoms in children. J Urol. 2000;164:1011–5.

    Google Scholar 

  • Fast AM, Nees SN, et al. Outcomes of targeted treatment for vesicoureteral reflux in children with nonneurogenic lower urinary tract dysfunction. J Urol. 2013;190:1028–33.

    Google Scholar 

  • Finnell SME, Carroll AE, et al. Diagnosis and management of an initial UTI in febrile infants and young children. Pediatrics. 2011;128. www.pediatrics.org/cgi/doi/10.1542/peds.2011-1332

  • Frimberger D, Mercado-Deane MG. Establishing a Standard Protocol for the Voiding Cystourethrography. Pediatrics. 2016;138(5):e20162590.

    Google Scholar 

  • Garin EH, Olavarria F, et al. Clinical significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after acute pyelonephritis: a multicenter, randomized, controlled study. Pediatrics. 2006;117:626–32.

    Google Scholar 

  • Georgaki-Andelaki H, Kostaridou S, et al. Long-term follow-up of children with vesicoureteral reflux with and without antibiotic prophylaxis. Scan J Inf Dis. 2005;37:842–5.

    Google Scholar 

  • Giannotti G, Menezes M, et al. Sibling vesicoureteral reflux in twins. Pediatr Surg Int. 2011;27:513–5.

    Google Scholar 

  • Giramonti KM, Fox JK, et al. Is parental anxiety and coping associated with girls’ distress during a VCUG? Preliminary findings. J Ped Urol. 2012;8:405–9.

    Google Scholar 

  • Gokce I, Alpay H, et al. Urinary levels of inteleukin-6 and interleukin-8 in patients with vesicoureteral reflux and renal parenchymal scar. Pediatr Nephrol. 2010;25:905–12.

    Google Scholar 

  • Goldraich NP, Goldraich IH. Follow up of conservatively treated children with high and low grade reflux: a prosepctive study. J Urol. 1992;148:1688.

    Google Scholar 

  • Grazioli S, Parvex P, et al. Antenatal and postnatal ultrasound in the evaluation of the risk of vesicoureteral reflux. Pediatr Nephrol. 2010;25:1687–92.

    Google Scholar 

  • Greenfield SP, Ng M, Wan J. Resolution rates of low grade vesicoureteral reflux stratified by patient age at presentation. J Urol. 1997a;157:1410.

    Google Scholar 

  • Greenfield SP, Ng M, Wan J. Experience with vesicoureteral reflux in children: clinical charactertistics. J Urol. 1997b;158:574.

    Google Scholar 

  • Greenfield SP, Carpenter MA, et al. The RIVUR voiding cystourethrogram pilot study: experience with radiologic reading concordance. J Urol. 2012;188:1608–128.

    Google Scholar 

  • Greenfield SP, Cheng E, DeFoor W, Kropp B, Rushton HG, Skoog S, Carpenter M. Vesicoureteral Reflux and Antibiotic Prophylaxis: Why Cohorts and Methodologies Matter. J Urol. 2016;196(4):1238–43.

    Google Scholar 

  • Herndon CDA, Ferrer F, McKenna P. Survey results on medical and surgical follow up of patients with vesicoureteral reflux from American Association of Pediatrics, Section on Urology members. J Urol. 2001;165:559.

    Google Scholar 

  • Hoberman A, Charron M, et al. Imaging studies after a first febrile urinary tract infection in young children. NEJM. 2013;348:195–202.

    Google Scholar 

  • Hoberman A, Greenfield SP, et al. Antimicrobial prophylaxis for children with vesicoureteral reflux. NEJM. 2014;370 https://doi.org/10.1056/NEJMoal401811.

  • Hunziker M, Puri P, et al. Familial vesicoureteral reflux and reflux related morbidity in relatives of index patients with high grade vesicorureteral reflux. J Urol. 2012;188:1463–6.

    Google Scholar 

  • Hunzker M, Colhoun E, et al. Renal cortical abnormalities in siblings of index patients with vesicorureteral reflux. Pediatrics. 2014;133:e933–7.

    Google Scholar 

  • Karami H, Razi A, et al. Is there a role for urodynamic study in children with high grade vesicoureteral reflux? Urology. 2012;79:888–91.

    Google Scholar 

  • Keir MJ, Lambert HJ, Coultard MG. Maximizing the sensitivity of the indirect radionuclide cystogram: a retrospective audit. Pediatr Nephrol. 2013;28:2137–41.

    Google Scholar 

  • Kelly H, Barton D, et al. Linkage analysis of candidate genes in families with vesicoureteral reflux. J Urol. 2009;182:1669–72.

    Google Scholar 

  • Kis E, Nyitrai A, Várkonyi I, et al. Voiding urosonography with second-generation contrast agent versus voiding cystourethrography. Pediatr Nephrol. 2010;25:2289–93.

    Google Scholar 

  • Kitchens DM, Herndon A, Joseph DB. Outcome after discontinuing prophylactic antibiotics in children with persistent vesicoureteral reflux. J Urol. 2010;184:1594–7.

    Google Scholar 

  • Leroy S, Boiussou F, et al. Prediction of high grade vesicoureteral reflux after pediatric urinary tract infection: external validation study of procalcitonin-based decision rule. PLoS One. 2011;6:e29556.

    Google Scholar 

  • Lytzen R, Thorup J, Cortes D. Experience with the NICE guidelines for imaging studies in children with first pyelonnephritis. Eur J Pediatr Surg. 2011;21:283–6.

    Google Scholar 

  • Mantadakis E, Vouloumanou EK, et al. Acute Tc-99m DMSA scan for identifying dilating vesicoureteral reflux in children: a meta-analysis. Pediatrics. 2010;128:e169–79.

    Google Scholar 

  • Marchini GS, Onal B, et al. Genome gender diversity in affected sib-pairs with familial vesico-ureteric reflux identified by single nucleotide polymorphism linkage analysis. BJU Inter. 2011;109:1709–14.

    Google Scholar 

  • Massanyi EZ, Preece J, et al. Utility of screening ultrasound after first febrile UTI among patients with clinically significant vesicoureteral reflux. Urol. 2014;82:905–9.

    Google Scholar 

  • Matsumoto F, Shimada K, et al. Positioning the instillation of contrast at the ureteral orifice cystography can be useful to predict postoperative contralateral reflux in children with unilateral reflux. Int J Urol. 2011;18:80–2.

    Google Scholar 

  • Menezes M, Puri P. Familial vesicoureteral reflux--is screening beneficial? J Urol 2009; 182:1673–1677.

    Google Scholar 

  • Metcalf CB, MacNeilly AE, et al. Reliability assessment of international grading system for vesicoureteral reflux. J Urol. 2012;188:1490–2.

    Google Scholar 

  • Montini G, Rigon L, et al. Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized controlled, noninferiority trial. Pediatrics. 2008;122:1064–71.

    Google Scholar 

  • Naseri M, Ghiggeri GM, et al. Five cases of severe vesico-ureteric reflux in a family with an X-linked compatible trait. Pediatr Nephrol. 2010;25:349–52.

    Google Scholar 

  • National Institute for health and clinical excellence: urinary tract infection in children. NICE 2007.; http://guidance.nice.org.uk/CG054

  • Nelson CP, Johnson EK, et al. Ultrasound as a screening test for genitourinary anomalies with UTI. Pediatrics. 2014;133:394–403.

    Google Scholar 

  • Oliviera EA, Diniz JSS, et al. Features of primary vesicoureteric reflux detected by investigation of foetal hydronephrosis. Int Urol Nephrol. 1998;30:535.

    Google Scholar 

  • Onal B, Miao X, et al. Protective locus against renal scarring on chromosome 11 in affected sib pairs with familial vesicoureteral reflux identified by single nucleotide polymorphism linkage analysis. J Urol. 2012;188:1467–73.

    Google Scholar 

  • Palmer BW, Faridali GR et al., Voiding cystourethrograms--are our protocols the same? J Urol 2011; 186: 1668–1671.

    Google Scholar 

  • Papadopoulou F, Anthopoulou A, Siomou E, et al. Harmonic voiding urosonography with a second-generation contrast agent for the diagnosis of vesicoureteral reflux. Pediatr Radiol. 2009;39:239–44.

    Google Scholar 

  • Pennesi M, Travan L, et al. Is antibiotic prophylaxis in children with vesicoureteral reflux effective in preventing pyelonephritis and renal scars? A randomized, controlled trial. Pediatrics. 2008;121:e1489–94.

    Google Scholar 

  • Quirino IG, Silva MP, et al. Combined use of late phase dimercaptosuccinic acid renal scintigraphy and ultrasound as first line screening after a urinary tract infection in children. J Urol. 2011;185:258–63.

    Google Scholar 

  • Roussey-Kesler G, Gadjos V, et al. Antibiotic prophylaxis for prevention of recurrent urinary tract infection in children with low grade vesicoureteral reflux: results from a prospective randomized study. J Urol. 2008;179:674–9.

    Google Scholar 

  • Rubenstein JN, Maizels M, et al. The PIC cystogram: a novel approach to identify “occult” vesicoureteral reflux in children with febrile urinary tract infections. J Urol. 2003;169:2339–43.

    Google Scholar 

  • Rushton HG, Majd M, et al. Renal scarring following reflux and non-reflux pyelonephritis in children: evaluation with technetium-dimercaptosuccinic acid scintigraphy. J Urol. 1992;147:1327.

    Google Scholar 

  • Sandy NS, Nguyen HT, et al. Assessment of parental satisfaction in children undergoing voiding cystourethrography without sedation. J Urol. 2011;185:658–62.

    Google Scholar 

  • Shaikh N, Hoberman A, et al. Identifying children with vesicoureteral reflux: a comparison of 2 approaches. J Urol. 2012;188:1895–9.

    Google Scholar 

  • Sjostrom S, Bachelard M, et al. Change of urodynamic patterns in infants with dilating vesicoureteral reflux: 3-year followup. J Urol. 2009;182:2446–54.

    Google Scholar 

  • Sjostrom S, Sillen U, et al. Predictive factors for resolution of congenital high grade vesicoureteral reflux in infants: results of univariate and multivariate analyses. J Urol. 2010;183:1177–84.

    Google Scholar 

  • Skoog SJ, Belman AB, Majd M. A non-surgical approach to the management of primary vesicoureteral reflux. J Urol. 1987;138:941.

    Google Scholar 

  • Skoog SJ, Peters CA, et al. Pediatric vesicoureteral reflux guidelines panel summary report: clinical practice guidelines for screening siblings of children with vesicoureteral reflux and neonates/infants with prenatal hydronephrosis. J Urol. 2010;184:1145–51.

    Google Scholar 

  • Snow BW. New non-invasive methods to diagnose vesicoureteral reflux. Curr Op in Urol. 2011;21:339–42.

    Google Scholar 

  • Sun HL, Wu KH, et al. Role of procalcitonin in predicting dilating vesicoureteral reflux in young children hospitalized with a first febrile urinary infection. Ped Inf Dis J. 2013;32:e 348-54.

    Google Scholar 

  • Szymanski KM, Al-Said AN, et al. Do infants with mild prenatal hydronephrosis benefit from screening for vesicoureteral reflux? J Urol. 2012;188:576–81.

    Google Scholar 

  • Tamminen-Mobius BE, et al. Cessation of vesicoreteral reflux for 5 years in infants and children allocated to medical treatment. The international reflux study in children. J Urol. 1992;148(1662)

    Google Scholar 

  • Thompson RH, Chen JJ, et al. Cessation of prophylactic antibiotics in older children with vesicoureteral reflux. J Urol. 2001;166:1465.

    Google Scholar 

  • Tsai JD, Huang CT, et al. Screening high grade vesicoureteral reflux in young infants with a febrile urinary tract infection. Pediatr Nephrol. 2012;27:955–63.

    Google Scholar 

  • Tse NK, Yuen SL, et al. Imaging studies for the first urinary tract infection in infants less than 6 months old: can they be more selective? Pediatr Nephrol. 2009;24:1699–703.

    Google Scholar 

  • Vallee JP, Vallee MP, et al. Contemporary incidence of mobidity related to vesicoureteral reflux. Urology. 1999;53:812.

    Google Scholar 

  • Vasanawala SS, Kennedy WA, et al. MR voiding cystography for evaluation of vesicoureteral reflux. Am J Rad. 2009;192:W206–11.

    Google Scholar 

  • Verbitsky M, Krithivasan P, Batourina E, et al. Copy Number Variant Analysis and Genome-wide Association Study Identify Loci with Large Effect for Vesicoureteral Reflux. Am Soc Nephrol. 2021;32(4):805–20.

    Google Scholar 

  • Wan J, Greenfield SP, et al. Sibling reflux: a dual center retrospective study. J Urol. 1996;156:677.

    Google Scholar 

  • Wan J, Skoog S, et al. On behalf of the executive committee, section on urology, American Academy of Pediatrics: section on urology response to new guidelines for diagnosis and management of UTI. Pediatrics. 2012;129:e1051–3. URL: www.pediatrics.org/cgi/doi/10.1542/peds. 2011-3615

  • Wheeler D, Vimalachandra D, et al. Interventions for primary vesicoureteral reflux. Cochrane Database Syst Rev. 2004;3:CD001532.

    Google Scholar 

  • Williams G, Wei L, et al. Long term antibiotics for preventing recurrent urinary tract infection in children (review) the Cochrane collaboration in the Cochrane library. Norfolk: John Wiley & Sons, Ltd; 2009. p. 1–28.

    Google Scholar 

  • Yildiz B, Poyraz N, et al. High sensitive C-reactive protein: a new marker for urinary tract infection, VUR and renal scar. Eur Rev Med Pharmacol Sci. 2013:2598–604.

    Google Scholar 

  • Yilmaz A, Bilge I, et al. Matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in vesicoureteral reflux. Pediatr Nephrol. 2012;27:435–41.

    Google Scholar 

  • Zeissman HA, Majd M. Importance of methodology on 99m-technetium dimercaptosuccinic acid image quality: imaging pilot study for RIVUR (randomized intervention for children with vesicoureteral reflux) multicenter investigation. J Urol. 2009;182:272–9.

    Google Scholar 

  • Zhang X, Xu H, et al. Accuracy of early DMSA scan for VUR in young children with febrile UTI. Pediatrics. 2012;133:e30–8.

    Google Scholar 

  • Zhou TB, Lin N, et al. Association of ACE I/D gene polymorphism with vesicoureteral reflux susceptibility in children: a meta-analysis. J Ren Angio Aldo Syst. 2012;13:273–81.

    Google Scholar 

  • Zu S, Bartik Z, et al. Mutations in the ROBO2 and SLIT2 genes are rare causes of familial vesico-ureteral reflux. Pediatr Nephrol. 2009;24:1501–8.

    Google Scholar 

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Greenfield, S.P. (2022). The Diagnosis and Medical Management of Vesicoureteral Reflux: An Update and Current Controversies. In: Puri, P. (eds) Pediatric Surgery. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-38482-0_178-1

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