Paediatric Urology 2, North Western Deanery Urology Teaching Monday, 29 July 2013 Vesico-ureteric reflux Ivo Dukic, Zubeir Ali, Mr Guy Wemyss-Holden Introduction • Theory and background • Cases – EAU Guidelines – Key papers – Practical management – Discussion • Viva questions as we go along What is the most appropriate grade of vesico-ureteric reflux as per the international reflux study committee 1985? 12 year old boy, presented following a trauma, what is the most appropriate grade of vesico-ureteric reflux as per the international reflux study committee 1985? Background • Vesico-ureteric reflux is the: – “The non-physiological back-flow of urine from the urinary bladder into the ureter or the renal pelvis and calyces” • VUR can be divided into: – Primary = Congenital anomaly of VUJ – Secondary = Due to anatomical or functional bladder outflow obstruction with subsequent reflux e.g. Posterior urethral valves, spina bifida Coleman, R., 2011. Early management and long-term outcomes in primary vesicoureteric reflux. BJU international, 108 Suppl 2, pp.3–8. Epidemiology • • • • 1% of children 10 times as common in white children Newborns – M>F Higher grades of VUR in males and more spontaneous resolution • Children >1yrs – F 5-6x >M Case 1 • A 20 month girl has been referred to you from the GP following a febrile episode. The urine sample taken at the time has a confirmed E Coli UTI. • The mum tells you that she has had no problems since birth but there was a dilated kidney which was checked and resolved in the first 6 months • What are the causes for antenatal hydronephrosis? Case 1 • What are the causes for an antenatal hydronephrosis? • PUJ obstruction (40%) • VUJ obstruction or megaureter • Vesico-ureteric reflux – 16.2% (7-35%) – Posterior urethral valves (60% VUR) – Cloaca (60% VUR), Duplex kidney (46%) – Neurogenic bladder Tekgül, S. et al., 2013. EAU and ESPU guidelines on Paediatric Urology. European Association of Urology. Sung, J. & Skoog, S., 2012. Surgical management of vesicoureteral reflux in children. Pediatric Nephrology (Berlin, Germany), 27(4), pp.551–561 Case 1 • How do you investigate a child with hydronephrosis in the postnatal period? Case 1 • How do you investigate a child with hydronephrosis in the postnatal period? – Typically 7 days after birth – Immediately if bilateral, oligohydranmnios, solitary kidney, pulmonary hypoplasia – Renal USS – MAG 3 renography 4-6 week of life – VCUG recommended in bilateral hydronephrosis, ureterocele, ureteral dilation and abnormal bladders Case 1 • How would evaluate the patient? – Which factors are important? • History • Examination • Investigations Management goals 1. Prevent recurring febrile UTI 2. Main goal in management of patients with VUR is preservation of renal function 3. Minimise the morbidity of treatment and follow up Peters, C.A. et al., 2010. Summary of the AUA Guideline on Management of Primary Vesicoureteral Reflux in Children. The Journal of urology, 184(3), pp.1134–1144. Evaluation • Risk factors – Age – Sex – Reflux grade (VCUG) – Lower urinary tract dysfunction – Anatomic abnormalities – Kidney status Evaluation • • • • • Blood pressure Height and weight Urine for blood, proteinuria, bacteriuria Serum creatinine Renal USS and consider – VCUG – DMSA Investigations • EAU guidelines 2013 – VCUG recommend at age 0-2 year after first proven febrile UTI – If reflux diagnosed, DMSA recommended (usually for grade 3 and above) – In those with LUTD and febrile UTI, VCUG recommended at may have a worse final treatment outcome (Swedish Reflux Study 2010) – Performing a VCUG Investigations • Alternative “top down approach” - ESPR • • • • DMSA at time of febrile UTI VCUG if DMSA reveals renal involvement Misses VUR in 5-27%, Avoids unnecessary VCUG in >50% of screened Classification of VUR Lebowitz, R.L. et al., 1985. International system of radiographic Diamond, D.A. & Mattoo, T.K., 2012. Endoscopic Treatment of grading of vesicoureteric reflux. International Reflux Study in Primary Vesicoureteral Reflux. New England Journal of Children. Pediatric radiology, 15(2), pp.105–109. Medicine, 366(13), pp.1218–1226. Case 1 Grades? Abnormality? Why does lower pole system relfux more frequently? Diamond, D.A. & Mattoo, T.K., 2012. Endoscopic Treatment of Primary Vesicoureteral Reflux. New England Journal of Medicine, 366(13), pp.1218 1226. Case 1 • What management options would you recommend? Management options • Conservative therapy – – – – – – – VUR spontaneous resolution, watchful waiting Regular toileting, hygiene Urine surveillance Treat underlying bladder dysfunction Treat constipation Prompt treatment of breakthrough infections Repeat imaging as required VUR Prognosis Grade Spontaneous resolution over 5 year period I 82% II 80% III 46% IV 30% V 13% Coleman, R., 2011. Early management and long-term outcomes in primary vesicoureteric reflux. BJU international, 108 Suppl 2, pp.3–8. VUR - Prognosis • Resolution of VUR correlates with renal and bladder functional status – Yeung et al, 94% resolution with normal bladder function, 37% with abnormal renal function, none with abnormal bladder function • Older the child when VUR diagnosed the less likely their reflux will resolve • Secondary reflux has worse prognosis Yeung, C.K. et al., 2006. Renal and bladder functional status at diagnosis as predictive factors for the outcome of primary vesicoureteral reflux in children. The Journal of urology, 176(3), pp.1152–1156; discussion 1156–1157. Medical therapy • Intermittent antibiotic prophylaxis • Continues antibiotic prophylaxis (CAP) • Bladder rehabilitation in those with LUTD Management guidelines • All patients diagnosed in first year of life should be treated with CAP • Definitive surgical or endoscopic correction is preferred in those with frequent breakthrough infections • If presenting at 1-5 years of age – Grade 1-2 reflux and no symptoms, close surveillance without Abx prophylaxis may be an option – Grade 3-5 reflux, CAP is preferred option for initial therapy, surgical correction is reasonable alternative Case 2 • 4 year old boy with Grade III VUR diagnosed on VCUG at paediatric hospital • Referred with ballooning of the foreskin, possible balanitis and a febrile infection in the last 12 months Case 2 • What factors are important in evaluation? Evaluation • Risk factors – Age – Sex – Reflux grade (VCUG) – Lower urinary tract dysfunction – Anatomic abnormalities – Kidney status – Balanitis episodes, BXO, frequency of balanitis Case 2 • What management options are available for this patient? • What would you advise is the best management and why? Case 2 • Circumcision – NNT 4 to prevent febrile UTI in Grade 3 or above VUR – Alternative view, no difference in those undergoing Cohen procedure with or without circumcision Singh-Grewal, D., Macdessi, J. & Craig, J., 2005. Circumcision for the prevention of urinary tract infection in boys: a systematic review of randomised trials and observational studies. Archives of Disease in Childhood, 90(8), pp.853–858. Kwak, C. et al., 2004. Effect of circumcision on urinary tract infection after successful antireflux surgery. BJU international, 94(4), pp.627–629. Case 2 • You start the patient on CAP and arrange an early review in your clinic in 4 months time. However, the child is admitted twice in the next four months with a febrile UTI? • How would you proceed? Management options • Continue with CAP (alternate antibiotics) • Surgical treatment – Subureteral injection of bulking materials Grade Reflux resolution after one treatment 1 and 2 78.5% 3 72% 4 63% 5 51% Elder, J.S. et al., 2006. Endoscopic therapy for vesicoureteral reflux: a meta-analysis. I. Reflux resolution and urinary tract infection. The Journal of urology, 175(2), pp.716–722. STING and HIT procedures • • • • • • Endoscopic – STING (subureteric Teflon injection) O'Donnell and Puri 1986 75% success after one treatment. Few problems and can be repeated Learning curve Kirsh et al 2003. Safety in animals migration of particles to distant sites (brain and lung) • Other agents attempted but PTFE gives highest response rates; deflux (dextranomer hyaluronic coploymer) is the only FDA approved substance for endoscopic correction of Gd II-IV • HIT – Hydrodistention implantation technique Diamond, D.A. & Mattoo, T.K., 2012. Endoscopic Treatment of Primary Vesicoureteral Reflux. New England Journal of Medicine, 366(13), pp.1218–1226. HIT Double HIT 1 2 Swedish reflux trial • 203 children, age 1-2 years, grade III/IV reflux, randomised 3 treatments, 2 year follow up Endoscopic injection Antibiotic prophylaxis Surveillance Resolution 71% 39% 47% Febrile UTI 23% 19% 57% Scar formation 7% 0% 11% Brandström, P. et al., 2010. The Swedish reflux trial in children: IV. Renal damage. The Journal of urology, 184(1), pp.292–297. Case 3 • 1 year old girl who is asymptomatic referred by the paediatricians as her sister has been diagnosed with VUR • How would you evaluate and manage this patient? Primary VUR - Aetiology • Genetic basis for VUR – autosomal dominant • Siblings of patients with VUR have a 27% average prevalence of reflux • Offspring of parents with VUR have an almost 36% prevalence Peters, C.A. et al., 2010. Summary of the AUA Guideline on Management of Primary Vesicoureteral Reflux in Children. The Journal of urology, 184(3), pp.1134–1144. Tekgül, S. et al., 2012. EAU guidelines on vesicoureteral reflux in children. European urology, 62(3), pp.534–542. Sibling screening • Associated with lower grades • Significantly earlier resolution • If discovered with UTI, often high grade Sibling screening • EAU recommends informing parents of high prevalance of VUR in siblings and offspring • If screening perfomed, renal USS • VCUG recommended if evidence of renal scarring, or history of UTI • In toilet trained children no value in screening for VUR Tekgül, S. et al., 2012. EAU guidelines on vesicoureteral reflux in children. European urology, 62(3), pp.534–542. Case 4 • 6 year old girl referred by GP for management of VUR • Initial presentation at 1 year of age with temp of 39.2°C and irritability, E Coli in urine. Subsequent VCUG showed Grade IV VUR and renal scarring on USS. • Toilet trained at 2 years of age, antibiotics stopped at this point Case 4 • How would you assess the patient? Case 4 • Does she need further investigation? – Which investigations and why? Case 4 The parents have a number of concerns which the GP was unable to answer 1. Will the girls VUR resolve? Case 4 1. Should she have further treatment? 2. What circumstances would warrant further treatment? 3. What are the treatment options? Surgical Management • Cystoscopic – STING / HIT / Double HIT procedure • Open surgery – – – – Cohen Lich-Gregoir Glenn Anderson, Politano-Leadbetter Psoas hitch ureteroneocystostomy • Laparoscopic reflux correction Cohen cross trigonal (1975) Mure, P.-Y. & Mouriquand, P.D.E., 2004. Surgical Atlas The Cohen procedure. BJU International, 94(4), pp.679–698. Leadbetter Politano Steffens, J. et al., 2006. Surgical Atlas Politano-Leadbetter ureteric reimplantation. BJU International, 98(3), pp.695–712. Lich-Gregoir (extravesical) Riedmiller, H. & Gerharz, E.W., 2008. Antireflux surgery: Lich-Gregoir extravesical ureteric . tunnelling. BJU International, 101(11), pp.1467–1482 Laparoscopic Correction • Laparoscopic • Most well described Gil-Vernet procedure • Lower success rates than open procedures Success rates of surgery • 98% in some centres – Problems with ureteral obstruction – Contralateral obstruction or reflux • 10 year results of Internaional Reflux Study in Children concluded that no difference between ureteral reimplantation or antibiotic prophylaxis in those with Grade III/IV reflux <11 years Jodal, U. et al., 2006. Ten-year results of randomized treatment of children with severe vesicoureteral reflux. Final report of the International Reflux Study in Children. Pediatric Nephrology, 21(6), pp.785–792.