Vesicoureteric Reflux in Children—Current Concepts

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Urinary tract infection (UTI) is a common problem in infants and young children affecting about 2–5% of all small
children. Almost a third to half of infants who are inflicted with urinary infection are likely to have an abnormal urinary
tract, commonest of which is vesicoureteric reflux (VUR). Around 10–20% of children with VUR end with hypertension
or end stage renal disease stressing the need to diagnose and manage these children early. This article reviews
current status of clinical manifestations, diagnosis, and management of children with VUR.

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Vesicoureteric Reflux in Children—Current Concepts

  1. 1. Vesicoureteric Reflux in Children—Current Concepts
  2. 2. Apollo Medicine 2011 December Review Article Volume 8, Number 4; pp. 276–280 © 2011, Indraprastha Medical Corporation Ltd Vesicoureteric reflux in children—current concepts Anand Alladi*, Deepti Vepakomma** *Senior Consultant, Paediatric Surgery and Urology, **Consultant, Paediatric Surgery, Apollo Hospitals, Bengaluru, Karnataka, India. ABSTRACT Urinary tract infection (UTI) is a common problem in infants and young children affecting about 2–5% of all small children. Almost a third to half of infants who are inflicted with urinary infection are likely to have an abnormal urinary tract, commonest of which is vesicoureteric reflux (VUR). Around 10–20% of children with VUR end with hyperten- sion or end stage renal disease stressing the need to diagnose and manage these children early.This article reviews current status of clinical manifestations, diagnosis, and management of children with VUR. Keywords: Children, urinary tract infection, vesicoureteric reflux Correspondence: Dr. Anand Alladi, E-mail: alladianand@gmail.com doi: 10.1016/S0976-0016(11)60005-7 Urinary tract infection (UTI) is a common problem in infants and young children affecting about 2–5% of all small children. Boys are affected more in the neonatal period, and girls beyond 6 months of age. The chances of recurrent infection range from 1% to 3%, and this is more so in girls.1 Almost a third to half of infants who are inflicted with urinary infection are likely to have an abnormal urinary tract, predisposing them to infections. Vesicoureteric reflux (VUR) is the commonest pathology predisposing children to UTI.2 Such children need to be evaluated to protect fur- ther infections and damage to their kidneys. Vesicoureteric reflux is the abnormal retrograde pas- sage of urine from the bladder into the ureter. The incidence is around 1% of all children.3 Vesicoureteric reflux is reported to increase the risk of febrile UTI in children and be associated with impaired renal function in the long-term. Widespread use of obstetric ultrasonography has helped detect antenatal hydronephrosis accounting for 17–37%.4 The importance of diagnosing and treating VUR early can- not be but stressed as 10–20% of children with reflux neph- ropathy5 have hypertension or end-stage renal disease.6 Reflux can be primary or secondary to some bladder or its outlet pathology or dysfunction causing high-pressure systems. About 10–40% have primary VUR. There is a definite genetic basis for the development of primary reflux, which is borne out by the fact that nearly 30% of siblings and 70% of offsprings of children with VUR have the disease occurring in them.7 Those children who are not picked up antenatally may present with recurrent febrile UTI. In secondary VUR, they may present with symptoms of the primary diseases such as voiding difficulties and urodynamic symptoms. Occasionally, they may be present due to the sequelae of VUR such as hypertension, failure to thrive, and renal failure. Voiding cystourethrography (VCUG) is the gold standard for the diagnosis of VUR (Figures 1–6). The International Reflux Study Committee based on the degree of backflow and dilatation of the upper tract classifies VUR into five grades on VCUG9 : Grade 1 – Reflux only in ureter does not reach the pelvis. Grade 2 – Reflux up to pelvis with no dilation and normal fornices. Grade 3 – Mild to moderate dilatation of ureter with or without tortuosity, moderate dilation of collect- ing system with normal or blunting of fornices. Grade 4 – Moderate dilation of ureter with or without tortu- osity, moderate dilatation of collecting system with blunting of fornices but maintained papil- lary impressions. Grade 5 – Severe dilation with tortuosity of ureter and severe dilation of collecting system, clubbing of calyces, loss of papillary impressions and/or presence of intra-renal reflux.
  3. 3. Vesicoureteric reflux in children—current concepts Review Article 277 © 2011, Indraprastha Medical Corporation Ltd Figure 1 International Reflux Grading classification scheme for vesicoureteral reflux.8 I II III IV V Figure 3 Voiding cystourethrography showing posterior ure- thral valves with unilateral grade 5 vesicoureteric reflux, which spontaneously resolved 1 year after fulguration of valve. Mild prominence of the posterior urethra persists. Figure 4 Voiding cystourethrography showing right vesicouret- eric reflux and paraureteric diverticulum. Figure 5 Dimercaptosuccinic acid showing bilateral normal kidneys with no scars. Voiding cystourethrography is followed by a dimercap- tosuccinic acid cortical renogram to detect scarring and to document split renal function. Occasionally, additional investigations are required for diagnosing the primary pathology in secondary VUR. These include intravenous urography (IVU), CT, urodynamics, and cystoscopy. MANAGEMENT The main principles of management of VUR include early detection, monitoring, preventing infections, and allowing normal renal growth and preventing long-term sequelae. This is based on the natural history which shows spontane- ous resolution in nearly 90% for low-grade reflux and up to A B Figure 2 (A) Voiding cystourethrography showing left grade 3 and right grade 1 vesicoureteric reflux. (B) Voiding cystoure- thrography showing bilateral grade 5 vesicoureteric reflux with intra-renal reflux.
  4. 4. 278 Apollo Medicine 2011 December; Vol. 8, No. 4 Alladi and Vepakomma © 2011, Indraprastha Medical Corporation Ltd 70% in the bilateral grade 310 and the fact that sterile reflux is not harmful to the kidney. The mainstay of management is conservative with cyclical antibiotic prophylaxis, treatment of bladder dys- function, bladder training, urinary surveillance, serial assessment of blood pressure and renal functions, annual renal ultrasound, and VCUG and DMSA renogram till the resolution of reflux. The prophylactic antibiotic used is generally amoxicil- lin or cephalexin in neonates and young infants and tri- methoprim and nitrofurantoin in older children. The dose used is usually half to one-third of the therapeutic dose administered at bedtime. The International Reflux Study has found that children can be managed nonsurgically with little risk of new or increased renal scarring, provided they are maintained infection-free. The chance of spontaneous resolution of reflux is high in children <5 years with grades I–III reflux and in children <1 year (especially boys). Even higher grades of reflux (grades IV–V) may resolve spontaneously as long as they remain infection-free.10 The philosophy of medical management is based on the knowledge that low-grade reflux resolves spontaneously and sterile reflux does not damage the kidney. This involves administering long-term prophylactic antibiotics. Continuous antibacterial prophylaxis is said to decrease the incidence of pyelonephritis and subsequent renal scarring. Vesicoureteral Reflux Guideline Update Committee was set up by the AUA in 2005. They searched the MEDLINE® database from 1994 to 2008. The panel could not establish the effi- cacy of continuous antibiotic prophylaxis with current data. However, its purported lack of efficacy, as reported in the selected prospective clinical trials, is also unproven owing to significant limitations in these studies. In a recent Cochrane Database Systematic Review of 20 randomized control trials (RCTs) including 2324 chil- dren, it was found that long-term low-dose prophylactic antibiotics did not significantly decrease the incidence of recurrent symptomatic or febrile UTI, although there was considerable heterogeneity in the analyzes and only one study was adequately blinded. Antibiotic prophylaxis, however, decreased the risk of progressive or new damage on DMSA. There was also a 3-fold increase in the emergence of drug- resistance on long-term prophylaxis. Long-term prophylaxis in comparison to surgery or endoscopic correction with short- term (0–24 months) did not significantly reduce the risk of febrile infections.11 With more evidence now suggesting that patients with primary VUR also have an element of bladder dysfunction, the current focus is on managing this problem also. The measures include behavior modification protocol to ensure that the child empties his/her bladder completely at regular intervals (every 3 h), adequate hydration and constipation prevention. Anticholinergic medications are added where detrusor instability is documented.12,13 The American Urology Association treatment algorithm for the management of VUR is given in given in Figure 7. Surgical intervention is indicated in children with breakthrough infections despite prophylaxis or noncompli- ance to medical treatment. Relative indications include per- sistent high-grade reflux, associated congenital structural anomalies, appearance of new scars and girls with dilating reflux.There has been a wide spectrum of surgical techniques, using intravesical, extravesical, or combined techniques. However, the basic principle of all is to provide an anti-reflux Figure 6 Intravenous urography and dimercaptosuccinic acid showing right ureterocele in the bladder as filling defect and right duplex with poorly functioning upper moiety on dimer- captosuccinic acid. Diagnosis VUR grade I–II Patients 0–10 years (unilateral/bilateral) VUR cured or resolved Antibiotic prophylaxis Endoscopic implantation with NASHA/Dxgel VUR grade III–IV Patients 0–10 years (unilateral/bilateral) VUR grade V Patients <1 year (unilateral/bilateral) VUR grade V Patients 1–10 years (unilateral/bilateral) Open surgery Figure 7 American Urology Association treatment algorithm. VUR: vesicoureteric reflux; NASHA/Dxgel: non-animal stabi- lised hyaluronic acid/dextranomer gel.
  5. 5. Vesicoureteric reflux in children—current concepts Review Article 279 © 2011, Indraprastha Medical Corporation Ltd mechanism by creating an adequate submucosal tunnel. With advances in minimally invasive and robotic surgery, these surgeries are being carried out with minimum morbidity, faster recovery, and equally good results (Figure 8). Figure 8 Intravesical Cohen’s transtrigonal re-implantation for unilateral vesicoureteric reflux. Figure 9 (A, B) Endoscopic injection for vesicoureteric reflux— pre- and postinjection. A B Endoscopic treatment involves submucosal injection of a bulking agent into the bladder wall below the ureteral orifice, or within the ureteral tunnel, to provide tissue augmentation. The most commonly used substance nowa- days is a dextranomer/hyaluronic acid copolymer. This is technically easy and is a patient-friendly treatment modality. Success rates are slightly lower than in open surgery and a second or third injection of bulking agent is often necessary (Figure 9). The reported success range are 67.4% following single, 86.6% and 88.3% following second and third injections, respectively.14 A word of caution in analyzing these results—most of the resolutions and good results are documented in low-grade refluxes. REFERENCES 1. Marild S, Jodal U. Incidence rate of first time symptomatic urinary tract infections in children <6 years. Acta Paediatr 1998;87:549–52. 2. Dickinson JA. Incidence and outcome of symptomatic urinary tract infections in children. BMJ 1989;1:1330–2. 3. Bailey RR. Vesicoureteric reflux in healthy infants and chil- dren. In: Reflux Nephropathy Hodson CJ, Kincaid-Smith P, eds. New York: Masson 1979:59–61. 4. Zerin JM, Ritchey ML, Chang AC. Incidental vesicoureteric reflux in neonates with antenatally detected abnormalities. Radiology 1993;1187:157–60. 5. Goonasekara CD, Shah V, Wade AM, Barrett TM, Dillon MJ. 15 year followup in renin and blood pressure in reflux neph- ropathy. Lancet 1996;347:640–3. 6. Ardissino G, Avolio L, Dacco V, et al. Ital Kid Project. Longterm outcome of vesicoureteric reflux associated chronic renal failure in children. Data from Ital Kid Project. J Urol 2004;172:305–10. 7. Giel DW, Noehn, Williams MA. Ultrasound screening of asymptomatic siblings of children with vesicoureteric reflux: a longterm followup study. J Urol 2005;174:1602–4. 8. Gargollo PC, Diamond DA. Therapy insight: what nephrolo- gists need to know about primary vesicoureteral reflux. Nat Clin Prac Nephrol 2007;3:551–63. 9. International Reflux Committee—medical versus surgical treatment of primary vesicoureteric reflux. Paediatrics 1981; 67:392. 10. Smellii JM, Jodal U, Lax H, et al. Outcome of 10 year of severe vesicoureteric reflux managed medically: report of international reflux in children. J Paediatr 2001;139:656–63.
  6. 6. 280 Apollo Medicine 2011 December; Vol. 8, No. 4 Alladi and Vepakomma © 2011, Indraprastha Medical Corporation Ltd 11. Nagler EV, Williams G, Hodson EM, Craig JC. Interventions for primary vesicoureteric reflux. Update of Cochane Database Syst Rev 2007;3:CD001532. 12. Koff SA, Wagner TT, Jayanti VR. The relationship among dysfunctional elimination syndromes, primary vesicoureteric reflux and urinary tract infections in children. J Urol 1998; 160:1019–22. 13. Upadhay J, Bolduc S, Bagli DJ, et al. Use of dysfunctional void- ing symptom score to predict resolution of vesicoureteric reflux in children with voiding dysfunction. J Urol 2003;169:1842–6. 14. Chen HC, Yeh CM, Chou CM. Endoscopic treatment of vesicoureteric reflux in children with dextranomer/hyaluronic acid—a single surgeon’s 6 year experience. Diagnos Therap Endosc 2010 vol 10/278012:1–3.
  7. 7. Apollohospitals:http://www.apollohospitals.com/ Twitter:https://twitter.com/HospitalsApollo Youtube:http://www.youtube.com/apollohospitalsindia Facebook:http://www.facebook.com/TheApolloHospitals Slideshare:http://www.slideshare.net/Apollo_Hospitals Linkedin:http://www.linkedin.com/company/apollo-hospitals Blog:Blog:http://www.letstalkhealth.in/

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