Pediatric Urology The Management of Vesicoureteral Reflux in the Setting of Posterior Urethral Valve With Emphasis on Bladder Function and Renal Outcome: A Single Center Cohort Study Ali Tourchi, Abdol-Mohammad Kajbafzadeh, Zahra Aryan, and Maryam Ebadi OBJECTIVE METHODS RESULTS CONCLUSION To represent our experience in the management of posterior urethral valves and concomitant vesicoureteral reflux (VUR). A total of 326 children with posterior urethral valve who had underwent valve ablation/bladder neck incision were studied, and those who had persistent VUR and were categorized under 3 main groups were followed up. Group 1 (n ¼ 71) received prophylactic antibiotic, group 2 (n ¼ 50) underwent Deflux injection (2a) (n ¼ 28): Deflux injection alone, group 2b (n ¼ 22) Deflux with concomitant autologous blood injection (HABIT), and group 3 (n ¼ 19) underwent ureteroneocystostomy before referral and was followed up conservatively. VUR resolution, incidence of urinary tract infections (UTI), and bladder function were assessed. Mean duration of follow-up was 3.8 years; VUR resolution occurred in 66.1%, 86.0%, and 94.0% of groups 1-3, respectively (P ¼ .013). Resolution rate in group 2b was significantly higher than group 2a (90.9% vs 78.5%). Patients in group 2 experienced a longer UTI-free period compared with others (P <.05). Urodynamic studies demonstrated significant decrease in maximum voiding detrusor pressure and detrusor overactivity in all groups (P <.001). Children in group 3 ended up with lower compliance compared with others (P <.001). After toilet training, only 2.8%, 21.4%, 13.6%, and 27% children were diagnosed with lower urinary tract dysfunction in groups 1-3, respectively (P ¼ .027). Myogenic failure developed only in 3 boys in group 3. Ablation/bladder neck incision leads to significant improvement in VUR status in part because of improvement in bladder function. After successful valve removal, conservative therapy can be regarded as the mainstay of reflux treatment, whereas HABIT is recommended for high grade VUR associated with febrile UTI or deterioration in renal function. UROLOGY 83: 199e205, 2014. 2014 Elsevier Inc. P osterior urethral valves (PUV) are recognized as the most common cause of congenital urethral obstruction.1,2 Vesicoureteral reflux (VUR) secondary to PUV is known to affect the ultimate outcome of treatment and renal function status after correction of PUV1 and is present in up to 72% of cases. Therefore, management of VUR in these patients, where there is no standard approach, is of utmost importance. However, Financial Disclosure: The authors declare that they have no relevant financial interests. From the Division of Pediatric Urology, Brady Urological Institute, The Johns Hopkins Medical Institutions, Baltimore, MD; and the Pediatric Urology Research Center, Section of Tissue Engineering and Stem Cell Therapy, Department of Pediatric Urology, Children’s Pediatric Center of Excellence, Children’s Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran Reprint requests: Abdol-Mohammad Kajbafzadeh, M.D., Pediatric Urology Research Center, Section of Tissue Engineering and Stem Cell Therapy, Department of Pediatric Urology, Children’s Pediatric Center of Excellence, Children’s Hospital Medical Center, Tehran University of Medical Sciences, No. 62, Dr. Gharib’s Street, Keshavarz Boulevard, 1419433151 Tehran, Iran. E-mail: [email protected] Submitted: June 12, 2013, accepted (with revisions): July 24, 2013 ª 2014 Elsevier Inc. All Rights Reserved after successful correction of the obstruction, performing antireflux procedures for persistent high-grade VUR is recommended.2 Currently, various treatment strategies are available for correction of VUR consisting of the following: (1) conservative antibiotic prophylaxis; (2) open surgical treatment; (3) minimally invasive endoscopic treatment; and (4) observation or intermittent therapy with management of bladder/bowel dysfunction (BBD), in addition to treatment of urinary tract infections (UTI), as they occur.3 The management of concomitant VUR and PUV represents a unique challenge. This study aimed to present the follow-up of patients with PUV and concomitant VUR. VUR status was evaluated after ablation and bladder neck incision (ablation/BNI). Persistent VUR was managed with conservative antibiotic prophylaxis, injection of Deflux alone, or concomitant with autologous blood and ureteral reimplantation. 0090-4295/14/$36.00 http://dx.doi.org/10.1016/j.urology.2013.07.033 199 MATERIALS AND METHODS Study Population We retrospectively reviewed the medical records of children with PUV who underwent ablation/BNI as the initial management from April 1999 to November 2009. Those with evidence of VUR on preoperative voiding cystourethrogram (VCUG) and postoperative VUR within 3-6 months after successful ablation/BNI were included. All patients had been receiving Oxybutynin (0.2 mg/kg) and Baclofen for overactive bladder symptoms since ablation/BNI and yet presented with VUR. Exclusion criteria were the presence of complex urologic anomalies such as prune belly syndrome or duplex systems, age 15 years, or those who had not been monitored for at least a year (Sup 1). Children were managed conservatively (nonsurgical, group 1), underwent endoscopic Deflux injection (group 2), or ureteroneocystostomy (UNC; group 3). Our institutional review board approved this study. Adherence was defined on the basis of the patient’s compliance with physician’s recommendations and was expressed as the proportion of patients who proceeded in exact accordance with the recommendations. Data Acquisition Ultrasound evaluation of the urinary tract was performed for all children before obstruction relief, at first and sixth months postoperatively, then annually. Postoperative VCUG was obtained to ensure the absence of residual valve obstruction and to evaluate the status of VUR annually in those with persistent VUR. In patients who underwent surgical VUR correction, VCUG was obtained 3-6 months postoperatively. VUR was graded in accordance with the international system of radiographic grading of VUR in children.4 99Technetium dimercaptosuccinic acid scan was performed preoperatively and 6 months postoperatively. It was performed 6 months after documented UTI and a year thereafter. Relative kidney uptake of 45%-55% was considered normal, whereas mild, moderate, and severe renal function deterioration were defined as relative uptake between 40%-45%, 20%-40%, and less than 20%, respectively. Serum creatinine >1-2 mg/dL was considered as chronic renal failure (CRF), and the need for renal transplantation was regarded as end stage renal disease.5 Urodynamic studies (UDS) were performed before and 6 months after ablation/BNI and annually thereafter and was continued till normal urination. Maximum voiding detrusor pressure (Pdetmax), detrusor overactivity (DO), myogenic failure, dysfunctional voiding (DV), and bladder compliance were determined.6,7 Postvoid residual was considered significant if it exceeded 15% of the expected bladder capacity (EBC) (age >2:EBC ¼ [age (years) þ 2] 30, age <2:EBC ¼ weight (kg) 7)8 (Sup 2). Surgical Techniques and Interventions for VUR Management During postoperative follow-up, all patients received antibiotic prophylaxis (Cephalexin 15 mg/kg/night) till the disappearance of VUR. For those children who experienced febrile UTIs or deterioration in renal function during the first year after ablation/BNI, Deflux was injected. Conservative management with antibiotic prophylaxis (Cephalexin 15 mg/kg/night) was performed on patients in group 1 until spontaneous resolution of VUR. Endoscopic Deflux injection with autologous blood was performed in the presence of breakthrough UTIs in this 200 subgroup. To determine the exact resolution rate under conservative approach, last VUR state of these children before injection therapy was considered in our estimations. In group 2, endoscopic injection of Deflux was performed. One subgroup received solitary Deflux (group 2a) injection, whereas the other received Deflux and concomitant autologous blood injection (group 2b). The surgical technique has been previously described in detail.9,10,12,13 UNC was performed in a subset of patients (group 3) who were referred to our center from other primary and secondary centers; complete medical records were present at referral, and follow-up visits were performed at our center. Antibiotic treatment/prophylaxis, anticholinergic medication (Baclofen or Oxybutynin), a1-adrenergic antagonists (Terazosin or Prazosin), and biofeedback therapy were prescribed as indicated,14 which were the same in all 3 groups. Statistical Analysis Data analysis was performed using SPSS (version 16.0). Normally distributed variables were expressed as mean SD. Chi square test and analysis of variance were used to compare categorical and continues normally distributed variables among study groups, respectively. Fischer exact and Kruskal Wallis tests were performed when applicable. Kaplan-Meier method was used to compare the time to first occurrence of UTIs and CRF among study groups. Survival plots were drawn and log rank (Mantel-Cox) test was performed. All tests were 2-sided and a P value <.05 was considered statistically significant. Lost to follow-up after 1 year were not excluded, but the last data regarding VUR status and occurrence of UTI was included. UDS and dimercaptosuccinic acid scan were performed only as aforementioned; therefore, no estimation was used. RESULTS Demographics A total of 140 children with persistent VUR in 224 renal refluxing units after obstruction relief were included in the study (Sup 1). Mean age of patients was 2.7 3.1 years (range, 2 months-14 years). Mean duration of follow-up was 3.8 years (range, 2-6). Characteristics of the patients and mode of diagnosis are outlined in Table 1. In this historical cohort, 16 patients had concomitant ureteropelvic junction obstruction, and 7 had megaureter (4 with concomitant ureteropelvic junction obstruction and megaureter) in whom UNC was performed. Least adherence (54%) was seen in group 1, mostly because of refusal of repeat VCUGs and no compliance with antibiotic prophylaxis, whereas in groups 2 and 3, it was approximately 90% (Sup 1). Radiologic Evidence of VUR Correction No complications such as urethral stricture or valve residual were observed in immediate or repeat VCUGs after ablation/BNI. In addition to 75 patients (34%) with no sign of VUR on VCUG obtained within 6 months after ablation/BNI, 57 of 140 of the patients (40%) with persistent VUR experienced improvement from high grade (IV-V) to low grade (I-III) VUR. During follow-up, VUR resolution in group 1 was 66.1% and differed with UROLOGY 83 (1), 2014 Table 1. Demographics Group 2 Variable Group 1 No. (%) 2a No. (%) 2b No. (%) 14 9 2 2 1 12 5 1 2 2 Group 3 No. (%) Total No. (%) y Age ,* <1 33 (46.5) 1age<2 18 (25.3) 2age<5 10 (14.1) 5age<10 7 (9.9) 10age<15 3 (4.2) Mode of presentation* Antenatal 47 (66.1) diagnosis Incontinence 22 (30.9) Urine retention 7 (9.8) Fever/UTI 15 (21.2) Abdominal/ 2 (2.8) flank mass VUR gradey Grade I 1 (1.4)/30 (42.3) Grade II 5 (7.0)/23 (32.4) Grade III 13 (18.3)/5 (7.0) Grade IV 21 (29.6)/9 (12.7) Grade V 31 (43.7)/4 (5.6) Lateralityy Unilateral 23 (32.4)/31 (43.6) Bilateral 48 (67.6)/40 (56.4) (50.0) (32.1) (7.2) (7.2) (3.5) (54.7) (22.8) (4.5) (9.0) (9.0) 17 (60.7) 15 (68.1) 7 (25) 3 (10.7) 7 (25) 0 5 (22.7) 5 (22.7) 8 (36.3) 0 0/2 (7.1) 1 (3.6)/10 (35.7) 6 (21.4)/5 (17.9) 14 (50.0)/9 (32.1) 7 (25.0)/2 (7.1) 0/6 (27.3) 3 (13.6)/4 (18.2) 9 (40.9)/6 (27.3) 3 (13.6)/4 (18.2) 7 (31.8)/2 (9.1) 8 7 3 1 (42.1) (36.8) (15.8) (5.3) 0 13 (68.4) 9 2 5 1 (40.9) (10.4) (26.3) (5.2) 67 39 16 12 6 (47.9) (27.8) (11.4) (8.6) (4.3) 92 (65.7) 43 17 35 3 (30.7) (12.2) (25.0) (2.1) 1 (5.3)/7 (36.8) 2 (1.4)/45 (32.2) 5 (26.3)/2 (10.5) 14 (10)/39 (27.9) 2 (10.5)/3 (15.8) 30 (21.4)/19 (13.6) 6 (31.6)/4 (21.1) 44 (31.5)/26 (18.5) 5 (26.3)/3 (15.8) 50 (35.7)/11 (7.8) 6 (21.4)/10 (45.4) 7 (31.8)/9 (40.9) 7 (36.8)/6 (31.5) 43 (30.8)/56 (40) 22 (78.6)/18 (53.6) 15 (68.2)/13 (59.1) 12 (63.2)/13 (68.5) 97 (69.2)/84 (60) UTI, urinary tract infection; VUR, vesicoureteral reflux. * Mode of presentation that lead to the diagnosis before valve ablation and bladder neck incision. Of note, some patients had concomitant signs or symptoms. y VUR grade before and after valve removal for the patients fulfilled the selection criteria (before/after) has been depicted. VUR grade of patients in each group did not differ significantly before start the cohort (chi square test, P value ¼ .062). Other demographics of patients also did not differ significantly. Table 2. Spontaneous vesicoureteral reflux resolution on conservative management in group 1 Group 1: Conservative Management Variable First Year No (%) VUR resolution* Grade I Grade II Grade III Grade IV Grade V VUR improvement* Grade I Grade II Grade III Grade IV Grade V Second Year No (%) Third Year No (%) 0 0 0 0 0 10 (33.3) 2 (8.7) 0 0 0 24 (80.0) 9 (39.1) 1 (20.0) 0 0 25 15 1 2 (83.3) (65.2) (20.0) (22.2) 0 25 18 2 2 (83.3) (78.2) (40.0) (22.2) 0 0 0 0 0 0 10 (33.3) 2 (8.7) 0 0 0 24 9 1 1 25 15 3 2 1 (83.3) (65.2) (60.0) (22.2) (25.0) 25 18 4 4 1 (83.3) (78.2) (80.0) (44.4) (25) (80.0) (39.1) (20.0) (11.1) 0 Fourth Year No (%) Fifth Year No (%) Abbreviation as in Table 1. * All the enrolled patients had data at least for approximately 1 year after valve ablation and bladder neck incision. For the patients with more than 1 year follow-up vesicoureteral reflux (VUR) resolution or improvement has been defined with respect to the last voiding cystourethrogram. The resolution or improvement was stratified according to the voiding cystourethrogram results within 6 months after ablation/bladder neck incision. Improvement denotes to the no VUR or nondilating VUR (I-II) if patients had higher grades of IV-V. respect to grade (Table 2). In groups 2 and 3, VUR was eliminated in 86.0% and 94.0% of patients, respectively. Performing UNC led to a significant success in VUR resolution compared with other groups (P ¼ .013). Among patients in group 2, success in group 2b was significantly greater than group 2a (90.9% vs 78.5%, P ¼ .029, Sup 3). UROLOGY 83 (1), 2014 Infection and Renal Function Group 2 experienced a longer UTI-free period (Fig. 1). Of the patients, 28 of 71 (39.4%) in group 1, 2 of 28 (7.1%) in group 2a, 1 of 22 (4.5%) in group 2b, and 6 of 19 (31.5%) in group 3 experienced UTI during follow-up (P <.001). Febrile UTIs were observed in 10 of 71 (14.0%), 1 of 28 (3.5%), 0 of 22, and 3 of 19 (15.7%) of 201 Figure 1. (A) Time to occurrence of new cases of UTI, febrile UTI, and CRF. Children in goup 2 experienced more time free of any significant bacteriuria. (B) Left graph, % of EBC significantly decreased after ablation/BNI (P <.001, A arrow) and when VUR was corrected with surgical therapy within second year one significant reduction slope was seen (P <.001; B arrow). Middle graph, One significant reduction in Pdetmax (cm H2O) was observed after ablation/BNI (P <.001, A arrow). Another significant decrease was seen after surgical intervention for VUR correction in group 2 and 3 (P <.05, B arrow). First slope of decrease was sharper than second one indicates the pivotal role of ablation/BNI rather than surgical correction of VUR. Indeed, successful valve removal is also associated with considerable improvement in VUR. Right graph, DO significantly decreased after valve ablation/ BNI (P <.001, A arrow). No significant changes were observed after VUR management using 3 modalities, so no B arrow has been depicted. BNI, bladder neck incision; EBC, expected bladder capacity; DO, detrusor overactivity; Pdetmax, maximum voiding detrusor pressure; UTI, urinary tract infection; VUR, vesicoureteral reflux. (Color version available online.) patients in groups 1-3, respectively (P ¼ .126). Of the 10 patients in the conservative group with febrile UTI, 8 underwent endoscopic Deflux injection with concomitant autologous blood injection, in whom VUR was eliminated successfully in 5, and VUR grade improved to grade I in the remaining 3. New renal scarring was detected in 3 of 71 (4.2%), 0, 0, and 1 of 19 (5.2%) in groups 1-3, respectively (P ¼ .203). A total of 7 (9.8%), 2 (7.1%), 3 (13.6%), and 4 (21%) had CRF after ablation/ BNI (P ¼ .471), and last data of this cohort confirmed that 18 of 64 (28.1%), 2 of 24 (8.3%), 3 of 21 (14.2%), 6 of 18 (33.3%) had CRF in group 1-3, respectively (P ¼ .089). COMMENT Bladder Function Serial UDS were available for 27, 7, 6, and 14 children in groups 1-3, respectively. UDS demonstrated significant decrease in Pdetmax after valve removal (P <.001, Fig. 1B, middle graph). DO decreased significantly after ablation/ BNI (P <.001, Fig. 1B, right graph), and only 5 children In our referral center, VUR was detected in 256 of children (78%) with PUV, which corresponds to previous studies, reporting a 70% rate of secondary VUR among PUV patients.15 It is recommended that patients presenting with PUV undergo VCUG before ablation/ BNI.16 Increased storage and/or voiding pressures caused by lower urinary tract symptoms may lead to a spectrum of 202 in group 1 had persistent DO according to their final data. Bladder compliance increased and EBC decreased during follow-up. However, children in group 3 had lower compliance and high values of % of EBC in comparison with other groups (Figs. 1B, 3). No patient developed myogenic failure after ablation/BNI except 3 boys in group 3. After toilet training, only 2 (2.8%), 6 (21.4%), 3 (13.6%), and 5 children (27%) received diagnosis of DV in groups 1-3, respectively (P ¼ .027). DV was successfully eliminated using a-adrenergic antagonist and biofeedback in all of them except 2 patients in group 3. UROLOGY 83 (1), 2014 Figure 2. Bladder compliance increased significantly after ablation/BNI in all groups with respect to their baseline data; y ¼ (P <.001). Subsequently, it increases to normal level in all groups except group 3 that attain significance; * ¼ (P <.05). BNI, bladder neck incision. (Color version available online.) intravesical anatomic disorders possibly predisposing the patient to VUR. These symptoms are reported to delay spontaneous resolution of VUR and interfere with the outcome of endoscopic and surgical treatment.17 In this study, all patients had undergone ablation/BNI as the initial management. The authors perform BNI for all PUV patients. Although it may not be a common procedure, it is previously described that BNI concomitant with valve ablation reduces bladder hypercontractility effectively and prevents the development of myogenic failure in patients with PUV. In addition, it significantly decreases the need for anticholinergic therapy and clean intermittent catheterization and is recommended as the preferred treatment modality for children with PUV. Primary bladder neck dysfunction is usually associated with other forms of DV or might present with lower urinary tract symptoms and might be missed or treated incorrectly; this highlights the importance of performing BNI in the presence of PUV.6 In the present series, VCUG obtained within 6 months after ablation/BNI confirmed valve removal in all cases. No complication such as urethral stricture or valve residual was observed in immediate or repeat VCUGs. Spontaneous resolution of VUR was observed in 75 of patients (34%); in addition, 57 of 140 (40%) experienced improvement in VUR grade, from high (IV-V) to low (IIII), conferring to the secondary nature of VUR. This is comparable with valve ablation without BNI in which only 25% of reflux units improve to a lower grade16 and highlights the benefits of BNI as a complementary UROLOGY 83 (1), 2014 treatment modality for VUR secondary to PUV, in part because of bladder function correction. However, 66% of patients with the initial diagnosis of concomitant VUR and PUV in whom only ablation/BNI was performed, experienced VUR resolution during follow-up and presented better bladder outcome. This indicates that a considerable number of patients will experience VUR resolution in the long-term follow-up rather than in the short-term; it may be because of improvement in bladder function,6 as indicated by the absence of myogenic failure in our patients (Figs. 1, 2). Resolution rate differed with respect to the grade of VUR, implying that persistent high-grade reflux after valve ablation/BNI could not be corrected by conservative therapy alone and requires further interventions. Reflux nephropathy and decreased efficiency of ureteral urine transport caused by VUR are detrimental in patients with PUV.1 Therefore, in cases with persistent high-grade reflux after correction of obstruction, attempts must be made to correct the concomitancy.15 However, VUR should be corrected only in patients with recurrent febrile UTIs and deterioration in renal function, because rigorous treatment with reimplantation may lead to myogenic failure (only 3 boys in group 3 experienced myogenic failure in this study). In this study, VUR was managed by applying 3 different modalities as the following: observation, Deflux injection, and open repair. In a recent study conducted by Fast et al,18 no difference in the resolution of VUR was observed among different grades of secondary reflux; this finding is contrary to the results in primary cases; 203 additionally, they reported that despite primary grade V VUR, secondary high grade VURs can resolve with conservative therapy in some cases. The authors of the present study also disregard UNC, because many children who underwent UNC, were referred to our center because of complications such as obstruction despite radiologic elimination of VUR. However, we observed that concomitant Deflux and autologous blood injection can also eliminate VUR (90.9%) in children with febrile UTIs or deterioration in renal function without predisposing children to myogenic failure. Accordingly, patients in the conservative group in whom UTI was manifested underwent endoscopic Deflux injection. In addition, Deflux does not seem to harm compliance, with or without autologous blood, and can be effective even in higher grades of VUR. Therefore, in patients who undergo breakthrough infections and interventions are required for correction of the VUR, initial Deflux injection with/without autologous blood should be considered before any open surgery which might deteriorate bladder compliance. It bears mention that autologous blood injection after Deflux implantation, previously developed by the authors9,10,12,13 leads to clot formation and might prevent leakage, migration, or shrinkage of the mound. Moreover, the fibrin sealants in blood might contribute to mound preservation. Although considered a subtle change, 2 of the procedures reviewed here are not acknowledged as the standard of care. The mainstay of VUR treatment is to prevent renal parenchymal damage and morbidity associated with recurrent febrile UTIs.3,19 UNC was associated with better outcome on radiological findings compared with endoscopic and conservative therapy; however, no improvement in renal function was observed, conversely, it deteriorated in some cases. This could be explained by the fact that all patients in this group had urologic concomitancy (UVJO or megaureter) before ablation/BNI and also experienced postoperative complications; therefore, a selection bias might have occurred. In addition, referral bias can be acknowledged, because observation of UVJO concomitant with PUV is a rare combination, yet 16 cases were present in this study. In this study, no significant difference in renal outcome in terms of renal scarring was observed during our follow-up. Meanwhile, the incidence of UTI in patients receiving endoscopic Deflux injection concomitant with autologous blood was significantly lower compared with those receiving UNC and conservative therapy, which were approximately 15%. The authors hypothesize that low compliance and complications jeopardizing bladder and renal function might be responsible factors for the occurrence of febrile UTIs and deteriorated renal function in patients with radiologic evidence of VUR correction. In a recent study on 1551 children who had undergone antireflux surgery, bowel and bladder dysfunction, presenting before or after successful VUR correction, were found to be important risk factors for the development of febrile UTI.20 Interestingly, 204 DeFoor et al21 suggested that bladder dysfunction is a strong predictor of end stage renal disease in children with PUV. Once valve was removed successfully, all patients experienced significant improvement of bladder function, as observed on UDS and indicated by significant decrease in Pdetmax and DO, accompanied by complete resolution of myogenic failure (with the expectation of 3 cases in group 3). This finding is in accordance with other studies and implies that improvement in urodynamic variables and bladder function is dependent on valve ablation rather than reflux correction; however, VUR would be corrected after improvement in bladder function.6-22 All urodynamic parameters showed significant resolution after ablation/BNI. Resolution in Pdetmax and detrusor function showed significant correlation with both obstruction and reflux resolution, conferring that reflux might be secondary to obstruction and resolved after ablation, whereas resolution in myogenic function, which is interpreted from improvement in the residual and bladder volume, was only correlated to obstruction relief. Significant DV is observed in 13%-38% of boys after valve ablation23 and 20% of children with primary VUR will develop DV after toilet training.24 This study suggests that 11.4% of children with persistent VUR after ablation/BNI will develop DV. Several studies have reported the prognostic importance of voiding dysfunction in VUR cases.19,25,26 Glassberg et al27 reported that one-third of children with DV or idiopathic DO disorder were found to have VUR. In our study, a significant resolution in DV was observed after intervention, which ranged from approximately 3% in group 1 to 27% in group 3; all were successfully treated using a-adrenergic antagonist and biofeedback, except 2 patients in group 3. Giurici and Pennesi28 suggested investigation for BBD before correction of VUR in patients with VUR older than 3 years. As it is believed that reflux and relapsing UTI can occur secondary to BBD, hence correction of the dysfunction results in spontaneous resolution of VUR without the need for surgical interventions. Therefore, Oxybutynin and baclofen for overactive bladder symptoms were prescribed to all patients after ablation/BNI. In this study, poor bladder compliance was not observed in those who underwent concomitant Deflux and autologous blood injection, whereas 31.57% of whom UNC was performed experienced poor bladder compliance during the followup. It seems that bladder function is a key determinant of renal outcome in children with VUR secondary to PUV.29 Accordingly, attempts should be focused on correction of bladder function rather than performing invasive procedures for the correction of the radiologic findings regarding VUR. In addition to possible selection and referral bias that may have affected our results, other limitations that should be acknowledged are as follows; as serial VCUG studies were not pursued once VUR was absent, unless the patient became symptomatic, we stayed within the limits of detecting new-onset or recurrent VUR. The small number of patients with UDS may UROLOGY 83 (1), 2014 provide limitations when comparing LUT function among groups. Overall, conservative therapy can be regarded as the mainstay of reflux treatment after successful valve correction as it is associated with a 66% success rate and no significant renal scarring. It provides the opportunity to avoid invasive surgery and hospital stay. However, when persistent high-grade reflux is observed after performing valve ablation/BNI and also for patients noncompliance with repeat VCUGs or conservative antibiotic prophylaxis, endoscopic injection (with concomitant autologous blood) is recommended as the mainstay intervention. Finally, UNC cannot guarantee preservation of renal and bladder function even with correction of VUR. CONCLUSION Once valve ablation/BNI has been performed, conservative antibiotic therapy is preferred for persistent VUR secondary to PUV, as it has the benefit of low cost, no surgical morbidity, and a 66% spontaneous resolution rate. However, in persistent high-grade VUR with febrile UTIs or deterioration in renal function, endoscopic Deflux injection by performing concomitant autologous blood injection technique is preferred. Rigorous approach to persistent VUR with UNC may cause myogenic failure. References 1. Sarhan OM, El-Ghoneimi AA, Helmy TE, et al. Posterior urethral valves: multivariate analysis of factors affecting the final renal outcome. J Urol. 2011;185:2491-2495. 2. Kim YH, Horowitz M, Combs AJ, et al. Management of posterior urethral valves on the basis of urodynamic findings. J Urol. 1997; 158:1011-1016. 3. Hunziker M, Mohanan N, D’Asta F, et al. Incidence of febrile urinary tract infections in children after successful endoscopic treatment of vesicoureteral reflux: a long-term follow-up. J Pediatr. 2012;160:1015-1020. 4. Lebowitz RL, Olbing H, Parkkulainen KV, et al. International system of radiographic grading of vesicoureteric reflux. International Reflux Study in Children. Pediatr Radiol. 1985;15:105-109. 5. Smith GH, Canning DA, Schulman SL, et al. The long-term outcome of posterior urethral valves treated with primary valve ablation and observation. J Urol. 1996;155:1730-1734. 6. Kajbafzadeh AM, Payabvash S, Karimian G. The effects of bladder neck incision on urodynamic abnormalities of children with posterior urethral valves. J Urol. 2007;178:2142-2149. 7. Neveus T, von Gontard A, Hoebeke P, et al. The standardization of terminology of lower urinary tract function in children and adolescents: report from the Standardisation Committee of the International Children’s Continence Society. J Urol. 2006;176: 314-324. 8. Androulakakis PA, Karamanolakis DK, Tsahouridis G, et al. Myogenic bladder decompensation in boys with a history of posterior urethral valves is caused by secondary bladder neck obstruction? BJU Int. 2005;96:140-143. 9. Kajbafzadeh AM, Tourchi A. Usefulness of concomitant autologous blood and dextranomer/hyaluronic acid copolymer injection to correct vesicoureteral reflux. J Urol. 2012;88:948-952. UROLOGY 83 (1), 2014 10. Kajbafzadeh AM, Tourchi A, Ebadi M. The outcome of initial endoscopic treatment in the management of concomitant vesicoureteral reflux and ureteropelvic junction obstruction. Urology. 2013;81:1040-1046. 11. Kajbafzadeh AM, Tourchi A, Aryan Z. Factors that impact the outcome of endoscopic correction of vesicoureteral reflux: a multivariate analysis. Int Urol Nephrol. 2012;45:1-9. 12. Kajbafzadeh AM, Aryan Z, Tourchi A, Alizadeh H. Longterm ultrasound appearance of concomitant autologous blood and Dextranomer/ Hyalurnic acid Copolymer implants: is it associated with successful correction of vesicoureteral reflux? Urology. 2012;81:407-413. 13. Kajbafzadeh AM, Tourchi A, Ebadi M. Reply. Urology. 2013;81: 1045-1046. 14. Chase J, Austin P, Hoebeke P, et al. The management of dysfunctional voiding in children: a report from the Standardisation Committee of the International Children’s Continence Society. J Urol. 2010;183:1296-1302. 15. Puri P, Kumar R. Endoscopic correction of vesicoureteral reflux secondary to posterior urethral valves. J Urol. 1996;156:680-682. 16. Hassan J, Pope JC, Brock JW, et al. Vesicoureteral reflux in patients with posterior urethral valves. J Urol. 2003;170:1677-1680. 17. Hong YK, Altobelli E, Borer JG, et al. Urodynamic abnormalities in toilet trained children with primary vesicoureteral reflux. J Urol. 2011;185:1863-1869. 18. Fast AM, Nees SN, Van Batavia JP, et al: Outcomes of vesicoureteral reflux in children with non-neurogenic lower urinary tract dysfunction with targeted treatment at their specific LUT condition. J Urol. 2013;190:1028-1033. 19. Tekgul S, Riedmiller H, Hoebeke P, et al. EAU guidelines on vesicoureteral reflux in children. Eur Urol. 2012;63:534-542. 20. Puri P, Kutasy B, Colhoun E, et al. Single center experience with endoscopic subureteral dextranomer/hyaluronic acid injection as first line treatment in 1,551 children with intermediate and high grade vesicoureteral reflux. J Urol. 2012;188:1485-1489. 21. DeFoor W, Clark C, Jackson E, et al. Risk factors for end stage renal disease in children with posterior urethral valves. J Urol. 2008;180: 1705-1708; discussion 1708. 22. Kajbafzadeh AM, Baradaran N, Sadeghi Z, et al. Vesicoureteral reflux and primary bladder neck dysfunction in children: urodynamic evaluation and randomized, double-blind, clinical trial on effect of [alpha]-blocker therapy. J Urol. 2010;184:2128-2133. 23. Ansari M, Gulia A, Srivastava A, et al. Risk factors for progression to end-stage renal disease in children with posterior urethral valves. J Ped Urol. 2010;6:261-264. 24. Homayoon K, Chen JJ, Cummings JM, et al. Voiding dysfunction: outcome in infants with congenital vesicoureteral reflux. Urology. 2005;66:1091-1094; discussion 1094. 25. Schwab CW, Wu HY, Selman H, et al. Spontaneous resolution of vesicoureteral reflux: a 15-year perspective. J Urol. 2002;168:25942599. 26. Sillen U, Brandstr€om P, Jodal U, et al. The Swedish reflux trial in children: V. Bladder dysfunction. J Urol. 2010;184:298-304. 27. Glassberg KI, Combs AJ, Horowitz M. Nonneurogenic voiding disorders in children and adolescents: clinical and videourodynamic findings in 4 specific conditions. J Urol. 2010;184:2123-2127. 28. Giurici N, Pennesi M. Importance of bladder bowel dysfunction in patients with urinary tract infection. Pediatrics. 2012;161:370. 29. Ghanem MA, Wolffenbuttel KP, De Vylder A, et al. Long-term bladder dysfunction and renal function in boys with posterior urethral valves based on urodynamic findings. J Urol. 2004;171: 2409-2412. APPENDIX SUPPLEMENTARY DATA Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.urology. 2013.07.033. 205
