Skip to main content
Log in

Febrile urinary tract infection, vesicoureteral reflux, and renal scarring: current controversies in approach to evaluation

  • Review Article
  • Published:
Pediatric Surgery International Aims and scope Submit manuscript

Abstract

The ideal approach to the radiological evaluation of children with urinary tract infection (UTI) is in a state of confusion. The conventional bottom-up approach, with its focus on the detection of upper and lower urinary tract abnormalities, including vesicoureteral reflux, has been challenged by the top-down approach, which focuses on confirming the diagnosis of acute pyelonephritis before more invasive imaging is considered. Controversies abound regarding which approach may best assess the ultimate risk for reflux-related renal scarring. Evolving practices motivated by the emerging evidence, the desire to minimize unnecessary interventions, as well as improve compliance with recommended testing, have added to the current controversies. Recent guideline updates and ongoing clinical trials hopefully will help in addressing some of these concerns.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Peters CA, Skoog SJ, Arant BS Jr et al (2010) Summary of the AUA Guideline on management of primary vesicoureteral reflux in children. J Urol 184:1134–1144

    Article  PubMed  Google Scholar 

  2. Hellstrom A, Hanson E, Hansson S et al (1991) Association between urinary symptoms at 7 years old and previous urinary tract infection. Arch Dis Child 66:232–234

    Article  PubMed  CAS  Google Scholar 

  3. Shortliffe LMD (2007) Infection and inflammation of the pediatric genitourinary tract. In: Wein AJ (ed) Campbell-Walsh Urology, 9th edn. Saunders Elsevier, Philadelphia (p Chapter 12)

    Google Scholar 

  4. Freedman AL (2007) Urinary tract infection in children. In: Litwin MS, Saigal CS (eds) Urologic diseases in America. US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Washington, DC, vol NIH Publication No. 07-5512, pp 439–457

  5. American Academy of Pediatrics. Committee on quality improvement (1999) Subcommittee on urinary tract infection: practice parameter: the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. Pediatrics 103:843–852

    Google Scholar 

  6. Keren R, Carpenter MA, Hoberman A et al (2008) Rationale and design issues of the randomized intervention for children with vesicoureteral reflux (RIVUR) study. Pediatrics 122(Suppl 5):S240–S250

    Article  PubMed  Google Scholar 

  7. Chesney RW, Carpenter MA, Moxey-Mims M et al (2008) Randomized intervention for children with vesicoureteral reflux (RIVUR): Background commentary of RIVUR investigators. Pediatrics 122(Suppl 5):S233–S239

    Article  PubMed  Google Scholar 

  8. Faust WC, Diaz M, Pohl HG (2009) Incidence of post-pyelonephritic renal scarring: a meta-analysis of the dimercapto-succinic acid literature. J Urol 181:290–297

    Article  PubMed  Google Scholar 

  9. Elder JS (2007) Vesicoureteral reflux. In: Kliegman RM, Behrman RE, Jenson HB et al (eds) Nelson Textbook of Pediatrics, 18th edn. Saunders Elsevier, Philadelphia (p Chapter 539)

  10. Orellana P, Baquedano P, Rangarajan V et al (2004) Relationship between acute pyelonephritis, renal scarring, and vesicoureteral reflux. Results of a coordinated research project. Pediatr Nephrol 19:1122–1126

    Article  PubMed  Google Scholar 

  11. Scott JE, Stansfeld JM (1968) Ureteric reflux and kidney scarring in children. Arch Dis Child 43:468–470

    Article  PubMed  CAS  Google Scholar 

  12. Hutch JA, Chisholm ER, Smith DR (1969) Summary of pathogenesis of, and new classification for urinary tract infection (and a report of 381 cases to which this classification has been applied). J Urol 102:758–761

    PubMed  CAS  Google Scholar 

  13. Filly RA, Friedland GW, Govan DE et al (1974) Urinary tract infections in children. Part II––Roentgenologic aspects. West J Med 121:374–381

    PubMed  Google Scholar 

  14. Skoog SJ, Belman AB, Majd M (1987) A nonsurgical approach to the management of primary vesicoureteral reflux. J Urol 138:941–946

    PubMed  CAS  Google Scholar 

  15. Jodal U, Smellie JM, Lax H et al (2006) Ten-year results of randomized treatment of children with severe vesicoureteral reflux. Final report of the international reflux study in children. Pediatr Nephrol 21:785–792

    Article  PubMed  Google Scholar 

  16. Elder JS, Peters CA, Arant BS Jr et al (1997) Pediatric Vesicoureteral Reflux Guidelines Panel summary report on the management of primary vesicoureteral reflux in children. J Urol 157:1846–1851

    Article  PubMed  CAS  Google Scholar 

  17. Lin KY, Chiu NT, Chen MJ et al (2003) Acute pyelonephritis and sequelae of renal scar in pediatric first febrile urinary tract infection. Pediatr Nephrol 18:362–365

    PubMed  Google Scholar 

  18. Ataei N, Madani A, Habibi R et al (2005) Evaluation of acute pyelonephritis with DMSA scans in children presenting after the age of 5 years. Pediatr Nephrol 20:1439–1444

    Article  PubMed  Google Scholar 

  19. Hewitt IK, Zucchetta P, Rigon L et al (2008) Early treatment of acute pyelonephritis in children fails to reduce renal scarring: data from the Italian Renal Infection Study Trials. Pediatrics 122:486–490

    Article  PubMed  Google Scholar 

  20. Coulthard MG, Verber I, Jani JC et al (2009) Can prompt treatment of childhood UTI prevent kidney scarring? Pediatr Nephrol 24:2059–2063

    Article  PubMed  Google Scholar 

  21. Coulthard MG (2002) Do kidneys outgrow the risk of reflux nephropathy? Pediatr Nephrol 17:477–480

    Article  PubMed  Google Scholar 

  22. Mingin GC, Nguyen HT, Baskin LS et al (2004) Abnormal dimercapto-succinic acid scans predict an increased risk of breakthrough infection in children with vesicoureteral reflux. J Urol 172:1075–1077

    Article  PubMed  Google Scholar 

  23. Martz K, Stablein DM, North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) (2008). Annual Report

  24. Estrada CR Jr, Passerotti CC, Graham DA et al (2009) Nomograms for predicting annual resolution rate of primary vesicoureteral reflux: results from 2, 462 children. J Urol 182:1535–1541

    Article  PubMed  Google Scholar 

  25. Mingin GC, Hinds A, Nguyen HT et al (2004) Children with a febrile urinary tract infection and a negative radiologic workup: factors predictive of recurrence. Urology 63:562–565

    Article  PubMed  Google Scholar 

  26. Hoberman A, Charron M, Hickey RW et al (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. Vachvanichsanong P, Dissaneewate P, Thongmak S et al (2008) Primary vesicoureteral reflux mediated renal scarring after urinary tract infection in Thai children. Nephrology (Carlton) 13:38–42

    Article  Google Scholar 

  28. Rushton HG, Majd M, Jantausch B et al (1992) Renal scarring following reflux and nonreflux pyelonephritis in children: evaluation with 99mtechnetium-dimercaptosuccinic acid scintigraphy. J Urol 147:1327–1332

    PubMed  CAS  Google Scholar 

  29. Majd M, Rushton HG, Jantausch B et al (1991) Relationship among vesicoureteral reflux, P-fimbriated Escherichia coli, and acute pyelonephritis in children with febrile urinary tract infection. J Pediatr 119:578–585

    Article  PubMed  CAS  Google Scholar 

  30. Mahant S, Friedman J, MacArthur C (2002) Renal ultrasound findings and vesicoureteral reflux in children hospitalised with urinary tract infection. Arch Dis Child 86:419–420

    Article  PubMed  CAS  Google Scholar 

  31. Bjorgvinsson E, Majd M, Eggli KD (1991) Diagnosis of acute pyelonephritis in children: comparison of sonography and 99mTc-DMSA scintigraphy. AJR Am J Roentgenol 157:539–543

    PubMed  CAS  Google Scholar 

  32. MacKenzie JR, Fowler K, Hollman AS et al (1994) The value of ultrasound in the child with an acute urinary tract infection. Br J Urol 74:240–244

    Article  PubMed  CAS  Google Scholar 

  33. Preda I, Jodal U, Sixt R et al (2010) Value of ultrasound in evaluation of infants with first urinary tract infection. J Urol 183:1984–1988

    Article  PubMed  Google Scholar 

  34. Cohen AL, Rivara FP, Davis R et al (2005) Compliance with guidelines for the medical care of first urinary tract infections in infants: a population-based study. Pediatrics 115:1474–1478

    Article  PubMed  Google Scholar 

  35. National Institute for Health and Clinical Excellence (NICE) (2007) Urinary tract infection in children: diagnosis, treatment and long-term management. Clinical guideline 54. August 2007. http://guidance.nice.org.uk/CG054. Accessed 2 August 2010

  36. Tse NK, Yuen SL, Chiu MC et al (2009) Imaging studies for first urinary tract infection in infants less than 6 months old: can they be more selective? Pediatr Nephrol 24:1699–1703

    Article  PubMed  Google Scholar 

  37. Riccabona M, Avni FE, Blickman JG et al (2008) Imaging recommendations in paediatric uroradiology: minutes of the ESPR workgroup session on urinary tract infection, fetal hydronephrosis, urinary tract ultrasonography and voiding cystourethrography, Barcelona, Spain, June 2007. Pediatr Radiol 38:138–145

    Article  PubMed  Google Scholar 

  38. Majd M, Nussbaum Blask AR, Markle BM et al (2001) Acute pyelonephritis: comparison of diagnosis with 99mTc-DMSA, SPECT, spiral CT, MR imaging, and power Doppler US in an experimental pig model. Radiology 218:101–108

    PubMed  CAS  Google Scholar 

  39. Hansson S, Dhamey M, Sigstrom O et al (2004) Dimercapto-succinic acid scintigraphy instead of voiding cystourethrography for infants with urinary tract infection. J Urol 172:1071–1073

    Article  PubMed  Google Scholar 

  40. Preda I, Jodal U, Sixt R et al (2007) Normal dimercaptosuccinic acid scintigraphy makes voiding cystourethrography unnecessary after urinary tract infection. J Pediatr 151:581–584

    Article  PubMed  Google Scholar 

  41. Siomou E, Giapros V, Fotopoulos A et al (2009) Implications of 99mTc-DMSA scintigraphy performed during urinary tract infection in neonates. Pediatrics 124:881–887

    Article  PubMed  Google Scholar 

  42. Herz D, Merguerian PA, Danielson C. Five-year prospective results of DMSA imaging in children with febrile urinary tract infection: proof the top-down approach works. 2009. 2009 American Academy of Pediatrics National Conference and Exhibition, 10-16-2009, Washington, DC

  43. Ziessman HA, Majd M (2009) Importance of methodology on (99m)technetium dimercapto-succinic acid scintigraphic image quality: imaging pilot study for RIVUR (randomized intervention for children with vesicoureteral reflux) multicenter investigation. J Urol 182:272–279

    Article  PubMed  Google Scholar 

  44. Khoury A, Bagli DJ (2007) Reflux and megaureter. In: Wein AJ (ed) Campbell-Walsh Urology, 9th edn. Saunders Elsevier, Philadelphia (p Chapter 117)

  45. Elder JS, Shah MB, Batiste LR et al (2007) Part 3: endoscopic injection versus antibiotic prophylaxis in the reduction of urinary tract infections in patients with vesicoureteral reflux. Curr Med Res Opin 23(Suppl 4):S15–S20

    Article  PubMed  Google Scholar 

  46. Garin EH, Olavarria F, Garcia NV et al (2006) Clinical significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after acute pyelonephritis:a multicenter, randomized, controlled study. Pediatrics 117:626–632

    Article  PubMed  Google Scholar 

  47. Montini G, Rigon L, Zucchetta P et al (2008) Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized, controlled, noninferiority trial. Pediatrics 122:1064–1071

    Article  PubMed  Google Scholar 

  48. Pennesi M, Travan L, Peratoner L et al (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 

  49. Roussey-Kesler G, Gadjos V, Idres N et al (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  PubMed  CAS  Google Scholar 

  50. Brandstrom P, Esbjorner E, Herthelius M et al (2010) The Swedish reflux trial in children: III. Urinary tract infection pattern. J Urol 184:286–291

    Article  PubMed  Google Scholar 

  51. Brandstrom P, Neveus T, Sixt R et al (2010) The Swedish reflux trial in children: IV. Renal damage. J Urol 184:292–297

    Article  PubMed  Google Scholar 

  52. Craig JC, Simpson JM, Williams GJ et al (2009) Antibiotic prophylaxis and recurrent urinary tract infection in children. N Engl J Med 361:1748–1759

    Article  PubMed  CAS  Google Scholar 

  53. Holmdahl G, Brandstrom P, Lackgren G et al (2010) The Swedish reflux trial in children: II. Vesicoureteral reflux outcome. J Urol 184:280–285

    Article  PubMed  Google Scholar 

  54. Peters CA (2010) Vesicoureteral reflux: seeing the trees in the forest. J Urol 184:8–9

    Article  PubMed  Google Scholar 

  55. Copp HL, Nelson CP, Shortliffe LD et al (2010) Compliance with antibiotic prophylaxis in children with vesicoureteral reflux: results from a national pharmacy claims database. J Urol 183:1994–1999

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Marie Sabo Recine, MS, for medical writing assistance. The authors wish to thank Oceana Therapeutics for their unrestricted educational grant, which allowed this activity to move forward.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Martin A. Koyle.

Appendices

Case study: bottom-up approach

A 3-year-old previously healthy, toilet-trained female with a normal prenatal ultrasound and unremarkable past medical history was diagnosed with her first febrile UTI, diagnosed with pyelonephritis, and treated promptly with oral antibiotics by her primary care physician. She was referred to Cincinnati Children’s Hospital and had a standard bottom-up evaluation. VCUG showed left-sided grade 2/5 reflux and large bladder capacity (400 mL), consistent with voiding dysfunction. Ultrasound showed a normal right kidney and abnormalities with some cortical loss, especially in the upper pole region, on the left. These findings prompted a DMSA scan, which showed a diffusely scarred left kidney that has lost approximately 40% of function.

There was some question as to whether there may have been other UTIs, but the parents kept meticulous records and there were no unexplained febrile illnesses or recurrent ear infections. The possibility was raised that the child may have had a higher grade of reflux at a younger age, with some of the scarring attributable to reflux nephropathy prior to infection. The pathologic bladder must also be considered.

Clinical context

There are patients who have a biologic susceptibility to renal injury, even from a single UTI. We owe these patients the ability to detect clinically significant reflux, and possibly treat it at a younger age to prevent ongoing injury.

Case study: top-down approach

A 15-year-old female with persistently elevated blood pressure was referred to the Children’s Hospital of Michigan Pediatric Nephrology department for further evaluation. There was nothing of significance in her past medical history/systemic review except for an episode of UTI and flank pain at the age of 12 years, which responded to oral antibiotic therapy. General physical exam was normal, as were routine lab investigations; ultrasound and Doppler flow study were normal. DMSA scan showed scarring in both kidneys, with left greater than the right. Differential uptake was 66% in the right kidney and 34% in the left. A nuclear VCUG showed left intrarenal reflux.

The patient was started on prophylactic antibiotic and enalapril. The patient underwent endoscopic injection therapy with dextranomer/hyaluronic acid (Dx/HA), after which the antibiotic prophylaxis was discontinued.

At 1-year follow-up, repeat VCUG showed absence of reflux. Blood pressure was well controlled on enalapril and urine protein was negative. Three years later, blood pressure remained well controlled and repeat DMSA showed no progression of renal scarring. The patient was transferred to an adult nephrologist at that time.

Clinical context

In an adolescent patient with hypertension and UTI, renal scarring is a potential possibility, thus, a top-down approach is favored.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koyle, M.A., Elder, J.S., Skoog, S.J. et al. Febrile urinary tract infection, vesicoureteral reflux, and renal scarring: current controversies in approach to evaluation. Pediatr Surg Int 27, 337–346 (2011). https://doi.org/10.1007/s00383-011-2863-y

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00383-011-2863-y

Keywords

Navigation