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Clinical presentation, diagnosis, and course of primary vesicoureteral reflux

Tej K Mattoo, MD, DCH, FRCP
Saul P Greenfield, MD
Section Editors
Laurence S Baskin, MD, FAAP
F Bruder Stapleton, MD
Deputy Editor
Melanie S Kim, MD


Vesicoureteral reflux (VUR) is the retrograde passage of urine from the bladder into the upper urinary tract. It is the most common urologic finding in children, occurring in approximately 1 percent of newborns, and as many as 30 to 45 percent of young children with a urinary tract infection (UTI) [1-3].

Current management is based upon the premise that VUR predisposes patients to acute pyelonephritis by transporting bacteria from the bladder to the kidney. Pyelonephritis itself is a morbid event that requires acute medical care and possible hospitalization in young infants. In addition, the resulting infection may lead to loss of renal parenchyma (renal scarring). Extensive scarring may progress to chronic kidney disease (CKD) (eg, hypertension, decreased renal function, proteinuria, and sometimes end-stage renal disease [ESRD]) [1,4-6]. However, this long-held belief that reflux in most instances may lead to progressive CKD and potentially ESRD has been increasingly questioned. As a result, the clinical impact of VUR and its management remain uncertain and controversial.

The diagnosis, presentation, and clinical course of primary VUR will be reviewed here. The management of primary VUR is discussed elsewhere in the program. (See "Management of vesicoureteral reflux".)


Vesicoureteral reflux (VUR) is divided into two categories: primary and secondary.

Primary VUR — Primary VUR, the most common form of reflux, is due to incompetent or inadequate closure of the ureterovesical junction (UVJ), which contains a segment of the ureter within the bladder wall (intravesical ureter). Normally, reflux is prevented during bladder contraction by fully compressing the intravesical ureter and sealing it off with the surrounding bladder muscles.


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Literature review current through: Jan 2017. | This topic last updated: Tue Aug 23 00:00:00 GMT+00:00 2016.
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  1. Dillon MJ, Goonasekera CD. Reflux nephropathy. J Am Soc Nephrol 1998; 9:2377.
  2. Shah KJ, Robins DG, White RH. Renal scarring and vesicoureteric reflux. Arch Dis Child 1978; 53:210.
  3. Smellie JM, Normand IC, Katz G. Children with urinary infection: a comparison of those with and those without vesicoureteric reflux. Kidney Int 1981; 20:717.
  4. Elder JS, Peters CA, Arant BS Jr, et al. Pediatric Vesicoureteral Reflux Guidelines Panel summary report on the management of primary vesicoureteral reflux in children. J Urol 1997; 157:1846.
  5. Blane CE, DiPietro MA, Zerin JM, et al. Renal sonography is not a reliable screening examination for vesicoureteral reflux. J Urol 1993; 150:752.
  6. Willi U, Treves S. Radionuclide voiding cystography. Urol Radiol 1983; 5:161.
  7. Ramage IJ, Schuckett B, McLorie GA, Geary DF. Primary vesicoureteric reflux diagnosed in the 1st month of life. Pediatr Nephrol 1999; 13:716.
  8. Willemsen J, Nijman RJ. Vesicoureteral reflux and videourodynamic studies: results of a prospective study. Urology 2000; 55:939.
  9. Hiraoka M, Hori C, Tsukahara H, et al. Vesicoureteral reflux in male and female neonates as detected by voiding ultrasonography. Kidney Int 1999; 55:1486.
  10. Ransley PG. Vesicoureteric reflux: continuing surgical dilemma. Urology 1978; 12:246.
  11. Hoberman A, Charron M, Hickey RW, et al. Imaging studies after a first febrile urinary tract infection in young children. N Engl J Med 2003; 348:195.
  12. Chand DH, Rhoades T, Poe SA, et al. Incidence and severity of vesicoureteral reflux in children related to age, gender, race and diagnosis. J Urol 2003; 170:1548.
  13. Montini G, Rigon L, Zucchetta P, et al. Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized, controlled, noninferiority trial. Pediatrics 2008; 122:1064.
  14. Roussey-Kesler G, Gadjos V, Idres N, et al. 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 2008; 179:674.
  15. Yeung CK, Godley ML, Dhillon HK, et al. The characteristics of primary vesico-ureteric reflux in male and female infants with pre-natal hydronephrosis. Br J Urol 1997; 80:319.
  16. RIVUR Trial Investigators, Hoberman A, Greenfield SP, et al. Antimicrobial prophylaxis for children with vesicoureteral reflux. N Engl J Med 2014; 370:2367.
  17. Skoog SJ, Peters CA, Arant BS Jr, 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.
  18. Kaefer M, Curran M, Treves ST, et al. Sibling vesicoureteral reflux in multiple gestation births. Pediatrics 2000; 105:800.
  19. Cordell HJ, Darlay R, Charoen P, et al. Whole-genome linkage and association scan in primary, nonsyndromic vesicoureteric reflux. J Am Soc Nephrol 2010; 21:113.
  20. Onal B, Miao X, Ozonoff A, 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.
  21. Zaffanello M, Tardivo S, Cataldi L, et al. Genetic susceptibility to renal scar formation after urinary tract infection: a systematic review and meta-analysis of candidate gene polymorphisms. Pediatr Nephrol 2011; 26:1017.
  22. Shaikh N, Spingarn RB, Hum SW. Dimercaptosuccinic acid scan or ultrasound in screening for vesicoureteral reflux among children with urinary tract infections. Cochrane Database Syst Rev 2016; 7:CD010657.
  23. Birkelund Y, Klemetsen Ø, Jacobsen SK, et al. Vesicoureteral reflux in children: a phantom study of microwave heating and radiometric thermometry of pediatric bladder. IEEE Trans Biomed Eng 2011; 58:3269.
  24. Arthurs OJ, Edwards AD, Joubert I, et al. Interactive magnetic resonance voiding cystourethrography (iMRVC) for vesicoureteric reflux (VUR) in unsedated infants: a feasibility study. Eur Radiol 2011; 21:1874.
  25. Fallah MM, Falahati M, Mohammadi A, et al. Comparative study of color Doppler voiding urosonography without contrast enhancement and direct radionuclide voiding cystography for diagnosis of vesicoureteric reflux in children. J Ultrasound Med 2012; 31:55.
  26. 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.
  27. 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.
  28. Keir MJ, Lambert HJ, Coulthard MG. Maximizing the sensitivity of the indirect radionuclide cystogram: a retrospective audit. Pediatr Nephrol 2013; 28:2137.
  29. D'Souza MK, Verma NS, A R PK, et al. Detecting reflux: does ureteric jet Doppler waveform have a role? Pediatr Nephrol 2013; 28:1821.
  30. Kis E, Nyitrai A, Várkonyi I, et al. Voiding urosonography with second-generation contrast agent versus voiding cystourethrography. Pediatr Nephrol 2010; 25:2289.
  31. Vasanawala SS, Kennedy WA, Ganguly A, et al. MR voiding cystography for evaluation of vesicoureteral reflux. AJR Am J Roentgenol 2009; 192:W206.
  32. Medical versus surgical treatment of primary vesicoureteral reflux: report of the International Reflux Study Committee. Pediatrics 1981; 67:392.
  33. Greenfield SP, Carpenter MA, Chesney RW, et al. The RIVUR voiding cystourethrogram pilot study: experience with radiologic reading concordance. J Urol 2012; 188:1608.
  34. Metcalfe CB, Macneily AE, Afshar K. Reliability assessment of international grading system for vesicoureteral reflux. J Urol 2012; 188:1490.
  35. Jaswon MS, Dibble L, Puri S, et al. Prospective study of outcome in antenatally diagnosed renal pelvis dilatation. Arch Dis Child Fetal Neonatal Ed 1999; 80:F135.
  36. Brophy MM, Austin PF, Yan Y, Coplen DE. Vesicoureteral reflux and clinical outcomes in infants with prenatally detected hydronephrosis. J Urol 2002; 168:1716.
  37. van Eerde AM, Meutgeert MH, de Jong TP, Giltay JC. Vesico-ureteral reflux in children with prenatally detected hydronephrosis: a systematic review. Ultrasound Obstet Gynecol 2007; 29:463.
  38. Herndon CD, McKenna PH, Kolon TF, et al. A multicenter outcomes analysis of patients with neonatal reflux presenting with prenatal hydronephrosis. J Urol 1999; 162:1203.
  39. Zerin JM, Ritchey ML, Chang AC. Incidental vesicoureteral reflux in neonates with antenatally detected hydronephrosis and other renal abnormalities. Radiology 1993; 187:157.
  40. Marra G, Barbieri G, Moioli C, et al. Mild fetal hydronephrosis indicating vesicoureteric reflux. Arch Dis Child Fetal Neonatal Ed 1994; 70:F147.
  41. Avni EF, Ayadi K, Rypens F, et al. Can careful ultrasound examination of the urinary tract exclude vesicoureteric reflux in the neonate? Br J Radiol 1997; 70:977.
  42. Yerkes EB, Adams MC, Pope JC 4th, Brock JW 3rd. Does every patient with prenatal hydronephrosis need voiding cystourethrography? J Urol 1999; 162:1218.
  43. Guarino N, Casamassima MG, Tadini B, et al. Natural history of vesicoureteral reflux associated with kidney anomalies. Urology 2005; 65:1208.
  44. Cascio S, Paran S, Puri P. Associated urological anomalies in children with unilateral renal agenesis. J Urol 1999; 162:1081.
  45. Nelson CP, Johnson EK, Logvinenko T, Chow JS. Ultrasound as a screening test for genitourinary anomalies in children with UTI. Pediatrics 2014; 133:e394.
  46. Massanyi EZ, Preece J, Gupta A, et al. Utility of screening ultrasound after first febrile UTI among patients with clinically significant vesicoureteral reflux. Urology 2013; 82:905.
  47. Vates TS, Shull MJ, Underberg-Davis SJ, Fleisher MH. Complications of voiding cystourethrography in the evaluation of infants with prenatally detected hydronephrosis. J Urol 1999; 162:1221.
  48. Hafez AT, McLorie G, Bagli D, Khoury A. Analysis of trends on serial ultrasound for high grade neonatal hydronephrosis. J Urol 2002; 168:1518.
  49. Silva JM, Santos Diniz JS, Marino VS, et al. Clinical course of 735 children and adolescents with primary vesicoureteral reflux. Pediatr Nephrol 2006; 21:981.
  50. Sjöström S, Sillén U, Jodal 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.
  51. Estrada CR Jr, Passerotti CC, Graham DA, et al. Nomograms for predicting annual resolution rate of primary vesicoureteral reflux: results from 2,462 children. J Urol 2009; 182:1535.
  52. Sjöström S, Sillén U, Bachelard M, et al. Spontaneous resolution of high grade infantile vesicoureteral reflux. J Urol 2004; 172:694.
  53. Godley ML, Desai D, Yeung CK, et al. The relationship between early renal status, and the resolution of vesico-ureteric reflux and bladder function at 16 months. BJU Int 2001; 87:457.
  54. Smellie JM, Jodal U, Lax H, et al. Outcome at 10 years of severe vesicoureteric reflux managed medically: Report of the International Reflux Study in Children. J Pediatr 2001; 139:656.
  55. Ismaili K, Hall M, Piepsz A, et al. Primary vesicoureteral reflux detected in neonates with a history of fetal renal pelvis dilatation: a prospective clinical and imaging study. J Pediatr 2006; 148:222.
  56. Upadhyay J, McLorie GA, Bolduc S, et al. Natural history of neonatal reflux associated with prenatal hydronephrosis: long-term results of a prospective study. J Urol 2003; 169:1837.
  57. Keren R, Shaikh N, Pohl H, et al. Risk Factors for Recurrent Urinary Tract Infection and Renal Scarring. Pediatrics 2015; 136:e13.
  58. Jacobson SH, Eklöf O, Eriksson CG, et al. Development of hypertension and uraemia after pyelonephritis in childhood: 27 year follow up. BMJ 1989; 299:703.
  59. el-Khatib MT, Becker GJ, Kincaid-Smith PS. Reflux nephropathy and primary vesicoureteric reflux in adults. Q J Med 1990; 77:1241.
  60. Claësson I, Jacobsson B, Jodal U, Winberg J. Compensatory kidney growth in children with urinary tract infection and unilateral renal scarring: an epidemiologic study. Kidney Int 1981; 20:759.
  61. Lahdes-Vasama T, Niskanen K, Rönnholm K. Outcome of kidneys in patients treated for vesicoureteral reflux (VUR) during childhood. Nephrol Dial Transplant 2006; 21:2491.
  62. Mattoo TK, Chesney RW, Greenfield SP, et al. Renal Scarring in the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) Trial. Clin J Am Soc Nephrol 2016; 11:54.
  63. Patterson LT, Strife CF. Acquired versus congenital renal scarring after childhood urinary tract infection. J Pediatr 2000; 136:2.
  64. Wennerström M, Hansson S, Jodal U, Stokland E. Primary and acquired renal scarring in boys and girls with urinary tract infection. J Pediatr 2000; 136:30.
  65. Marra G, Oppezzo C, Ardissino G, et al. Severe vesicoureteral reflux and chronic renal failure: a condition peculiar to male gender? Data from the ItalKid Project. J Pediatr 2004; 144:677.
  66. Ishikura K, Uemura O, Hamasaki Y, et al. Insignificant impact of VUR on the progression of CKD in children with CAKUT. Pediatr Nephrol 2016; 31:105.
  67. Murawski IJ, Gupta IR. Vesicoureteric reflux and renal malformations: a developmental problem. Clin Genet 2006; 69:105.
  68. Caione P, Ciofetta G, Collura G, et al. Renal damage in vesico-ureteric reflux. BJU Int 2004; 93:591.
  69. Swerkersson S, Jodal U, Sixt R, et al. Relationship among vesicoureteral reflux, urinary tract infection and renal damage in children. J Urol 2007; 178:647.
  70. 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; 126:1084.
  71. Hannula A, Perhomaa M, Venhola M, et al. Long-term follow-up of patients after childhood urinary tract infection. Arch Pediatr Adolesc Med 2012; 166:1117.
  72. Shaikh N, Craig JC, Rovers MM, 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; 168:893.
  73. Peters CA, Skoog SJ, Arant BS Jr, et al. Summary of the AUA Guideline on Management of Primary Vesicoureteral Reflux in Children. J Urol 2010; 184:1134.
  74. Tekgül S, Riedmiller H, Hoebeke P, et al. EAU guidelines on vesicoureteral reflux in children. Eur Urol 2012; 62:534.
  75. Routh JC, Grant FD, Kokorowski P, et al. Costs and consequences of universal sibling screening for vesicoureteral reflux: decision analysis. Pediatrics 2010; 126:865.
  76. Hunziker M, Puri P. Familial vesicoureteral reflux and reflux related morbidity in relatives of index patients with high grade vesicoureteral reflux. J Urol 2012; 188:1463.
  77. Hunziker M, Colhoun E, Puri P. Renal cortical abnormalities in siblings of index patients with vesicoureteral reflux. Pediatrics 2014; 133:e933.
  78. Wan J, Greenfield SP, Ng M, et al. Sibling reflux: a dual center retrospective study. J Urol 1996; 156:677.
  79. Menezes M, Puri P. Familial vesicoureteral reflux--is screening beneficial? J Urol 2009; 182:1673.