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Utility of Follow-up Renal Sonography in Children With Vesicoureteral Reflux and Normal Initial Sonogram

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Utility of Follow-up Renal Sonography in Children With Vesicoureteral

Reflux and Normal Initial Sonogram

Lisa H. Lowe, MD*; Manish N. Patel, DO*; John M. Gatti, MD‡; and Uri S. Alon, MD§

ABSTRACT. Objective. The purpose of this study was to determine the value of follow-up renal sonogra-phy in children who presented with urinary tract infec-tion and were found to have a voiding cystogram diag-nosis of vesicoureteral reflux while having a normal initial renal sonogram.

Methods. We retrospectively reviewed the medical records of 64 consecutive children who presented for follow-up renal sonography with a voiding cystogram diagnosis of vesicoureteral reflux and a normal initial sonogram conducted as part of the routine evaluation after urinary tract infection. Data recorded included gen-der, age, initial grade of reflux, time to follow-up sono-gram, and abnormalities on follow-up sonogram. Chil-dren with conditions that may predispose to vesicoureteral reflux were excluded.

Results. Children who were studied (7 boys, 57 girls) ranged in age from 1 month to 10 years, 10 months (mean: 35.6 months; median: 24 months). Ninety-four (73.4%) of 128 renal units demonstrated vesicoureteral reflux on voiding cystogram; 89 (94.7%) of 94 of them were grade 1 to 3. The mean time to follow-up was 22 months (range: 4 months to 5 years, 2 months; median: 18 months). All 128 (95% confidence interval: 0%–2.8%) renal units were normal on follow-up sonography.

Conclusion. Routine performance of repeat sonogra-phy seems unnecessary among children, particularly girls, with low- to medium-grade vesicoureteral reflux, who have had a previous normal sonogram and no con-ditions that predispose to vesicoureteral reflux. Pediat-rics 2004;113:548 –550; vesicoureteral reflux, sonography, urinary tract infection, kidneys, prophylactic antimicro-bials.

T

he initial uroradiologic approach to infants and young children with febrile urinary tract infec-tions, including voiding cystourethrography and renal sonography, is unequivocally recom-mended by such organizations as the American Academy of Pediatrics, the American Academy of Family Practice, the American College of Emergency Physicians, the American Urological Association, and the American College of Radiology.1,2The goal

of these imaging studies is to identify anatomic and

functional abnormalities that may place patients at risk for recurrent infection and kidney damage. Ul-trasound is used as an adjunct to voiding cystogra-phy to detect abnormal renal size, thinning of the parenchyma (scarring), obstruction, and hydrone-phrosis. Because children with vesicoureteral reflux are at risk for renal scarring, which, if severe, can be associated with significant morbidity, renal sonogra-phy is often periodically repeated, often with each subsequent voiding cystourethrogram. However, there is little guidance regarding follow-up imaging beyond periodic voiding cystography until vesi-coureteral reflux has resolved spontaneously or per-sisted significantly enough to warrant surgical cor-rection.3

It has been our impression that if a renal ultra-sound is initially normal in a child with history of urinary tract infections, then repeat ultrasounds rarely deteriorate in the setting of primary vesi-coureteric reflux. The purpose of this study was to determine the utility of follow-up renal ultrasound in the setting of known vesicoureteral reflux and a nor-mal initial sonogram.

METHODS

A departmental computerized scheduling database identified 64 consecutive children from May 2001 to March 2002 (11 months) who were scheduled for follow-up renal sonography after having a normal initial sonogram and diagnosis of vesicoureteral reflux based on fluoroscopic voiding cystogram. Demographic data (age and gender) were recorded in addition to grade of reflux on initial voiding cystogram, renal size on initial and last follow-up sono-gram, time between initial and last follow-up sonosono-gram, abnormal findings on last follow-up sonogram, use of prophylactic antimi-crobials, spontaneous resolution of reflux on cystogram during the study period, surgical intervention, and presence of recurrent infection.

Only children with primary reflux were included in the study. Specifically, children with known conditions that may predispose to vesicoureteral reflux, such as neurogenic bladder, ureteroceles, obstructive uropathy, renal duplication, and dysplasia, were ex-cluded from the study. In children who had multiple follow-up sonograms, only the last sonogram result was used for data anal-ysis.

All sonograms were performed using HDI 5000 ultrasound machines (Phillips Medical Systems, Bothell, WA). Sonograms and fluoroscopic voiding cystograms were initially interpreted by 1 of 6 pediatric radiologists. Follow-up sonograms were also reviewed retrospectively a second time by another pediatric radiologist to confirm the normal initial result. Renal size was measured in a longitudinal plane and compared with published standards.4

Grading of vesicoureteral reflux was based on the criteria of the International Reflux Study in Children.5

For the purpose of data analysis, each kidney was considered a “renal unit,” and all patients had 2 kidneys. StatXact 3.0 software (Cytel Software, Cambridge, MA) was used to calculate the con-fidence interval based on the binomial distribution.

From the *Department of Radiology, Children’s Mercy Hospital and Uni-versity of Missouri, Kansas City, Missouri; ‡Department of Pediatric Uro-logic Surgery, Children’s Mercy Hospital and University of Missouri, Kan-sas City, Missouri; and §Department of Nephrology, Children’s Mercy Hospital and University of Missouri, Kansas City, Missouri.

Received for publication Dec 6, 2002; accepted Jul 14, 2003.

Reprint requests to (L.H.L.) Department of Radiology, Children’s Mercy Hospital, 2401 Gillham Rd, Kansas City, MO 64108. E-mail: lhlowe@ cmh.edu

PEDIATRICS (ISSN 0031 4005). Copyright © 2004 by the American Acad-emy of Pediatrics.

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RESULTS

The study group included 128 renal units in 7 male and 57 female children ranging in age from 1 month to 10 years, 10 months (mean: 35.6 months; median: 24 months) at presentation. Ninety-four renal units had vesicoureteral reflux on voiding cystogram (Ta-ble 1). All 128 renal units were normal on initial and follow-up sonography (95% confidence interval: 0%– 2.8%). The time from the initial normal sonogram to the last follow-up sonogram ranged from 4 months to 5 years, 2 months (mean: 22 months; median: 18 months).

Fifty-two (81.25%) of 64 children received prophy-lactic antibiotics, 10 did not, and in 2 this information could not be obtained. Vesicoureteral reflux resolved during the study period in 64 renal units (42 chil-dren). In 42 (65.63%) of 64 renal units (28 children; average age: 4 years, 10 months), reflux resolved spontaneously (4 grade 1, 27 grade 2, 10 grade 3, 1 grade 4). In 14 children (mean age: 6 years, 9 months). reflux resolved in 22 (34.38%) of 64 renal units as a result of surgical intervention (3 grade 1, 10 grade 2, 7 grade 3, and 2 grade 4). Recurrent infection was documented in 14 (21.88%) of 64 children, with 9 (64.28%) of the 14 being managed surgically.

DISCUSSION

Urinary tract infection is the most common occult bacterial infection in febrile infants and young chil-dren. In 25% to 35% of this population, vesicoureteral reflux is detected.1,2Children with vesicoureteral

re-flux and upper urinary tract infection are at in-creased risk of pyelonephritis, which may lead to parenchymal scarring.2,6 –9Moderate to severe

paren-chymal scarring can be associated with hypertension and, although rare, renal insufficiency.8,10,11It is the

current recommendation to keep infants and young children with vesicoureteral reflux on long-term pro-tective antibiotics.10,11

Ninety-five percent of our population had grade 3 reflux or lower, with none having grade 5 vesi-coureteral reflux. By selecting a cohort of patients with reflux but no initial ultrasound abnormality, children with higher grades of vesicoureteral reflux, namely grades 4 and 5, may have been eliminated, by definition, from our study. Because it has been shown that higher grades of reflux are more com-monly associated with renal scarring and reflux ne-phropathy, it is not surprising that renal scars were not seen on follow-up in our study population. Fur-thermore, although the results of our study apply more to children with lower grades of reflux, others have also noted a low likelihood of developing renal scarring while on antibiotic suppression, as is the

routine in our institution, despite the grade of re-flux.12–16Indeed, recent studies from Sweden17and

our own institution18 demonstrated the drastic

de-cline of recurrent urinary tract infections as cause of pediatric chronic renal failure. This phenomenon has been attributed to early diagnosis and treatment of urinary tract infection with potent antibiotics by community pediatricians and family physicians, thus decreasing the risk of scar development.19,20 We

were able to confirm implementation of prophylactic antimicrobials in 81.25% of our patients. However, the number of patients who did not receive antimi-crobials was too small to conclude that they may not be needed.

Although reflux resolved spontaneously in 42 (44.7%) of 94 renal units (28 children) during the mean 22-month study period, we cannot determine the potential number that may have resolved spon-taneously beyond this point. Reflux resolved as a result of surgical intervention in another 22 (23%) of 94 renal units (14 children). This group of children who were treated by surgery was composed of older children with an average age at the time of surgery of 6 years, 9 months, as compared with 28 children who were not treated surgically with spontaneous resolu-tion of reflux documented on voiding cystogram (av-erage age: 4 years, 10 months). In addition, recurrent infection was documented in 14 (21.88%) of 64 chil-dren, and in 9 (64%) of these 14 chilchil-dren, surgery was performed. Renal sonography, nonetheless, re-mained normal in all of the above subgroups of spontaneous resolution of reflux, surgical interven-tion, and recurrent infection.

Our study found that the yield of follow-up ultra-sound in children with urinary tract infection, vesi-coureteral reflux of low to medium grade, and initial normal sonogram is negligible. It is possible that minimal scarring would have been detected by other, more sensitive means, such as cortical renal scintig-raphy, computed tomogscintig-raphy, or magnetic reso-nance imaging.21,22 However, the clinical relevance

of such mild scarring has never been proved.22

This study is limited by its retrospective nature and reflects the experience of a single children’s ter-tiary referral institution. The majority of our patients were female, reflecting the prevalence of reflux as a whole. These results are more compelling when con-sidering sonographic imaging follow-up in younger girls with vesicoureteral reflux of low to medium grade and a normal initial sonogram. The mean time to follow-up was 22 months, and we cannot deter-mine possible findings that may have occurred be-yond this period. Nevertheless, in some cases, clini-cal judgment, in particular history of recurrent infection, persistent reflux in older children, or pres-ence of voiding dysfunction, may still indicate the need for repeat follow-up sonograms.

CONCLUSION

Routine performance of repeat sonography seems unnecessary among children, particularly girls, with low- to medium-grade vesicoureteral reflux, who have had a previous normal sonogram and no con-ditions that predispose to vesicoureteral reflux.

TABLE 1. Initial Grades of Vesicoureteral Reflux Grade of

Vesicoureteral Reflux

n(Renal Units)

Grade 1 8/94 (8.5%)

Grade 2 55/94 (58.5%) Grade 3 26/94 (27.7%)

Grade 4 5/94 (5.3%)

Grade 5 0/94 (0.0%)

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REFERENCES

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2. Gelfand MJ, Parker BR, Kushner DC, et al. Urinary tract infection. American College of Radiology. ACR Appropriateness Criteria. Radiol-ogy.2000;215(suppl):847– 854

3. Elder JS, Peters CA, Arant BS Jr, et al. Pediatric Vesicoureteral Reflux Guidelines Panel summary report on the management of primary vesi-coureteral reflux in children.J Urol. 1997;157:1846 – 851

4. Han BK, Babcock DS. Sonographic measurements and appearance of normal kidneys in children.AJR Am J Roentgenol. 1985;145:611– 616 5. Lebowitz RL, Olbing H, Parkkulainen KV, Smellie JM,

Tamminen-Mobius TE. International system of radiographic grading of vesi-coureteric reflux. International Reflux Study in Children.Pediatr Radiol. 1985;15:105–109

6. Benador D, Benador N, Slosman D, Mermillod B, Girardin E. Are younger children at highest risk of renal sequelae after pyelonephritis?

Lancet. 1997;349:17–19

7. Lavocat MP, Granjon D, Allard D, Gay C, Freycon MT, Dubois F. Imaging of pyelonephritis.Pediatr Radiol. 1997;27:159 –165

8. Smellie JM, Normand IC, Katz G. Children with urinary infection: a comparison of those with and those without vesicoureteric reflux. Kid-ney Int. 1981;20:717–722

9. Merrick MV, Notghi A, Chalmers N, Wilkinson AG, Uttley WS. Long-term follow up to deLong-termine the prognostic value of imaging after urinary tract infections. Part 2: scarring.Arch Dis Child. 1995;72:393–396 10. Beetz R, Schulte-Wissermann H, Troger J, et al. Long-term follow-up of children with surgically treated vesicorenal reflux: postoperative inci-dence of urinary tract infections, renal scars and arterial hypertension.

Eur Urol. 1989;16:366 –371

11. Cooper A, Atwell J. A long-term follow-up of surgically treated vesi-coureteric reflux in girls.J Pediatr Surg.1993;28:1034 –1036

12. Benador D, Benador N, Slosman DO, Nussle D, Mermillod B, Girardin E. Cortical scintigraphy in the evaluation of renal parenchymal changes in children with pyelonephritis.J Pediatr. 1994;124:17–20

13. Tasker AD, Lindsell DR, Moncrieff M. Can ultrasound reliably detect renal scarring in children with urinary tract infection? Clin Radiol. 1993;47:177–179

14. Smellie JM, Ransley PG, Normand IC, Prescod N, Edwards D. Devel-opment of new renal scars: a collaborative study.Br Med J (Clin Res Ed). 1985;290:1957–1960

15. Smellie JM, Poulton A, Prescod NP. Retrospective study of children with renal scarring associated with reflux and urinary infection.Br Med J. 1994;308:1193–1196

16. Smellie JM, Jodal U, Lax H, Mobius TT, Hirche H, Olbing H. Outcome at 10 years of severe vesicoureteric reflux managed medically: report of the International Reflux Study in Children.J Pediatr. 2001;139:656 – 663 17. Esbjorner E, Berg U, Hansson S. Epidemiology of chronic renal failure in children: a report from Sweden 1986 –1994. Swedish Pediatric Ne-phrology Association.Pediatr Nephrol. 1997;11:438 – 442

18. Sreenarasimhaiah S, Hellerstein S. Urinary tract infections per se do not cause end-stage kidney disease.Pediatr Nephrol. 1998;12:210 –213 19. Hellerstein S, Nickell E. Prophylactic antibiotics in children at risk for

urinary tract infection.Pediatr Nephrol. 2002;17:506 –510

20. Panaretto K, Craig J, Knight J, Howman-Giles R, Sureshkumar P, Roy L. Risk factors for recurrent urinary tract infection in preschool children.J Paediatr Child Health. 1999;35:454 – 459

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

22. Sreenarasimhaiah V, Alon US. Uroradiologic evaluation of children with urinary tract infection: are both ultrasonography and renal cortical scintigraphy necessary?J Pediatr. 1995;127:373–377

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DOI: 10.1542/peds.113.3.548

2004;113;548

Pediatrics

Lisa H. Lowe, Manish N. Patel, John M. Gatti and Uri S. Alon

and Normal Initial Sonogram

Utility of Follow-up Renal Sonography in Children With Vesicoureteral Reflux

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DOI: 10.1542/peds.113.3.548

2004;113;548

Pediatrics

Lisa H. Lowe, Manish N. Patel, John M. Gatti and Uri S. Alon

and Normal Initial Sonogram

Utility of Follow-up Renal Sonography in Children With Vesicoureteral Reflux

http://pediatrics.aappublications.org/content/113/3/548

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Figure

TABLE 1.Initial Grades of Vesicoureteral Reflux

References

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