Renal and bladder functional status at diagnosis as predictive factors for the outcome of primary vesicoureteral reflux in children

PURPOSE: We studied the relationship between renal and bladder functional status at diagnosis and spontaneous resolution of reflux in young children with primary vesicoureteral reflux. MATERIALS AND METHODS: Children with grade III or greater vesicoureteral reflux were recruited for the study. At entry each patient underwent voiding cystourethrogram, renal ultrasound, isotope renogram, and natural filling and conventional filling urodynamic studies. Patients were then divided into 4 groups-group 1 had normal renal and bladder function, group 2 had abnormal renal and normal bladder function, group 3 had normal renal and abnormal bladder function, and group 4 had abnormal renal and bladder function. Correlation between renal and bladder functional status with reflux resolution at a minimum followup of 24 months was evaluated. RESULTS: A total of 82 patients (mean age 3.8 years) were prospectively evaluated and followed. There were 18 patients (13 males and 5 females) in group 1, 19 (13 and 6) in group 2, 19 (18 and 1) in group 3 and 26 (22 and 4) in group 4. Complete resolution of vesicoureteral reflux occurred in 17 patients (94%) in group 1 and 7 (37%) in group 2. None of the patients from group 3 or group 4 achieved complete vesicoureteral reflux resolution. Reflux grade remained unchanged in 15 patients (79%) in group 3 and 20 (77%) in group 4. CONCLUSIONS: Resolution of vesicoureteral reflux significantly correlated with renal and bladder functional status at diagnosis. Normal renal and bladder function at diagnosis is highly predictive of complete resolution of vesicoureteral reflux, whereas abnormal renal and bladder function is prognostic for persistence of reflux.     

Evaluation of antibody class in response to endoscopic subureteral collagen injection in patients with vesicoureteral reflux

PURPOSE: Clinical problems after glutaraldehyde cross-linked collagen injection for vesicoureteral reflux are the appearance of anticollagen antibodies and a decrease in collagen with time. We evaluated whether antibody production affects reflux recurrence and implanted collagen absorption. MATERIALS AND METHODS: We treated 27 patients (39 ureters) who had vesicoureteral reflux with endoscopic subureteral glutaraldehyde cross-linked collagen injection. The maximum diameter of the elevated ureteral orifice was measured 3-dimensionally and the numerical value calculated by multiplying each diameter by approximately pi/6 was used as the ultrasound estimate of injected collagen volume. The 1-to-6-month collagen volume ratio was used as an index of the decrease in implant collagen volume. The antibody class against bovine collagen was characterized by indirect enzyme-linked immunosorbent assay. RESULTS: Seroconversion in 6 patients was noted a mean 6.8 months after the first injection. In these patients the antibody class was IgG dominant and IgA or IgM was not detected. There was no significant difference in the total injected collagen volume, total number of injections or collagen volume ratio in the seropositive and seronegative groups. Reflux recurred in 4 patients and the curve of the reflux-free rate was similar regardless of antibody appearance. CONCLUSIONS: The immune response to bovine collagen injection for vesicoureteral reflux does not depend on injected collagen volume or an increased number of treatments. Antibody production had no effects on absorption of the implanted collagen or reflux recurrence.     

Screening siblings for vesicoureteral reflux

PURPOSE: Publications on screening the siblings of patients with reflux were reviewed to determine the overall incidence and severity of reflux and renal scarring in siblings, and identify factors that predict siblings more likely to have reflux. MATERIALS AND METHODS: A MEDLINE search for 1985 to the present was performed. Of 34 articles on familial reflux only 11, including 1 abstract, on sibling screening were used in this analysis. RESULTS: The mean incidence of reflux in siblings in all studies was 32% (570 of 1,768). Of the siblings with reflux approximately two-thirds had grades I to II disease. Only 22 of 1,051 siblings (2%) had reflux greater than grade III. Reflux was unilateral in 162 of 307 cases (53%). Certain factors predicted the chance of sibling reflux. Sibling age varied inversely with the incidence of reflux. A twin relationship and absent dysfunctional voiding symptoms in the index patient may predict a higher chance of reflux in a sibling. The mean incidence of renal abnormality in siblings with reflux was 11%. The incidence of reflux and renal abnormality in the sibling population undergoing screening was 3%. In more than half of the siblings with an abnormal renal evaluation there was no history of urinary tract infection. CONCLUSIONS: The studies reveal an incidence of reflux in siblings greater than in the general population. These data do not prove that screening and treating asymptomatic siblings decreases infectious renal scarring. Studies in a control group that consider sibling age are still needed to determine the benefit of screening asymptomatic siblings.     

Endoscopic treatment with dextranomer-hyaluronic acid for vesicoureteral reflux: histological findings

PURPOSE: Dextranomer-hyaluronic acid co-polymer is the first endoscopic bulking agent approved for vesicoureteral reflux in the United States. We evaluated the histopathological changes associated with this treatment in children with vesicoureteral reflux. MATERIALS AND METHODS: Children 1 to 11 years old in whom treatment with dextranomer-hyaluronic acid co-polymer for grades III or greater vesicoureteral reflux had failed were eligible for the study. Failure was defined as persistent vesicoureteral reflux on voiding cystourethrography done approximately 3 months after implantation. At ureteral reimplantation the implant and surrounding ureteral tissue were resected and fixed for histopathological analysis. Tissue sections (4 to 5 microm.) were stained for routine histology and examined under a light microscope. Patients with a similar grade of vesicoureteral reflux who had not undergone endoscopic treatment served as the control group. RESULTS: The study population comprised 23 patients with vesicoureteral reflux, of whom 13 with a mean age of 2 years 8 months at diagnosis underwent 1 to 3 treatments with dextranomer-hyaluronic acid co-polymer. The remaining 10 patients with a mean age of 1 year 10 months at diagnosis did not receive the bulking agent before ureteral reimplantation. The implant remained in situ 13 to 39 months (mean 22). On ureteral reimplantation the implant was located at the site of injection in 12 of the 13 patients. Histologically a granulomatous inflammatory reaction indicated by giant cell infiltration was observed at the implantation site. At ureteral reimplantation 9 implants were pseudo-encapsulated. Calcification was present in 9 ureters, while the eosinophil count was greater than 5 cells per 0.125 mm2 in 7 ureters treated with dextranomer-hyaluronic acid co-polymer. Mast cell infiltration was similar in the treatment and control groups. CONCLUSIONS: Endoscopic treatment with dextranomer-hyaluronic acid co-polymer for vesicoureteral reflux is associated with a granulomatous reaction of the giant cell type, inflammatory cell infiltration and implant pseudo-encapsulation. They are typical histological findings associated with implantation of a foreign material. Dextranomer-hyaluronic acid co-polymer remains safe and effective for vesicoureteral reflux in children.     

Endoscopic treatment of vesicoureteral reflux: 11 to 17 years of followup

PURPOSE: We review our 17-experience with endoscopic subureteral polytetrafluoroethylene injection for the treatment of primary vesicoureteral reflux in children. MATERIALS AND METHODS: We retrospectively reviewed the charts of 258 patients with primary vesicoureteral reflux who were treated with subureteral polytetrafluoroethylene injection from 1984 to 1990. RESULTS: The study included 205 girls and 53 boys between 3 months and 14 years old (median age 6 years). Of the patients 92 had unilateral vesicoureteral reflux, 129 had bilateral reflux and 37 had a refluxing duplex system including 6 with bilateral duplex systems. Endoscopic treatment by subureteral polytetrafluoroethylene injection was performed in 393 ureters. Reflux was corrected in 302 ureters (76.8%) after a single injection. Injection failed to stop reflux in 7 ureters (7 patients) and reimplantation was required. Patients were followed from 11 to 17 years with a mean followup plus or minus standard deviation of 13.5 +/- 3.4 years. Four patients were either lost to followup or parents refused to let them undergo voiding cystourethrography. Voiding cystourethrography in 247 patients with 379 ureters revealed that 360 ureters (95%) remain free of reflux whereas reflux recurred in 19 ureters (5%). Of these 19 ureters reflux was grade I or II in 13 for which no treatment was given and reflux was grade III or IV in 6, which required repeat injection. No untoward effects were seen in any of these patients with use of polytetrafluoroethylene as an injectable biomaterial. CONCLUSIONS: Endoscopic subureteral polytetrafluoroethylene injection is a simple and effective outpatient procedure for in the treatment of vesicoureteral reflux. No long-term morbidity was observed in our patients with small amounts of injectable polytetrafluoroethylene.     

Spontaneous resolution of vesicoureteral reflux: a 15-year perspective

PURPOSE: The spontaneous resolution rate of vesicoureteral reflux is helpful for determining the need for surgical intervention and the proper followup schedule in patients on antibiotic prophylaxis. We determined the resolution rate by patient rather than by ureter and analyzed the effects of laterality, gender, age and dysfunctional voiding. MATERIALS AND METHODS: We retrospectively reviewed the records of 179 girls and 35 boys who presented between 1981 and 1984 with urinary tract infection and were diagnosed with primary vesicoureteral reflux. Mean age at presentation was 4.2 years and median followup was 3 years. Of the patients 107 (50%) had bilateral reflux and 60 had dysfunctional voiding. In 146 children (68%) reflux spontaneously resolved during the study. Patients were categorized by the worst grade of reflux, maintained on antibiotic prophylaxis and underwent voiding cystourethrography yearly until reflux resolved. Kaplan-Meier curves were constructed to define the resolution rate. RESULTS: Grades I to III reflux resolved at 13% yearly during the initial 5 years of followup and then at 3.5% yearly during subsequent followup. Grade IV to V reflux resolved at 5% rate yearly. Bilateral reflux resolved more slowly than unilateral reflux and it resolved more rapidly in boys than in girls. Untreated dysfunctional voiding had no effect on overall resolution. CONCLUSIONS: Grades I to III primary vesicoureteral reflux diagnosed after urinary tract infection resolve at identical rates and significantly more rapidly than grades IV to V. Early repair of grade IV to V reflux should be considered after age 18 months.     

Outcome of sibling vesicoureteral reflux.

PURPOSE: We determine the efficacy of a prospective screening analysis of an asymptomatic sibling of patients with reflux. MATERIALS AND METHODS: A total of 78 siblings of patients with reflux were evaluated and 40 (51%) had reflux. The resolution rate and necessity for surgical intervention were evaluated. RESULTS: A total of 40 patients had vesicoureteral reflux, including grade I in 12, II in 33, III in 19 and IV in 1. No patient had gross renal scar on ultrasound or renal pelvis dysmorphism on voiding cystourethrogram. Treatment consisted of prophylactic antibiotics in all. One patient required surgical correction for breakthrough urinary tract infection. Followup was available in 31 patients, of whom reflux resolved completely with medical management in 26. Reflux was downgraded in 4 patients. Of the patients in whom reflux resolved completely grades I to II vesicoureteral reflux were in 18, and II to IV in 8. Mean time to resolution was 15.6 months. CONCLUSIONS: The incidence of sibling reflux is significant. However, grade specific time to resolution appears to be decreased compared to primary reflux diagnosed after urinary tract infection. Furthermore, the incidence of renal damage appears to be decreased compared to "traditional" reflux. Although it is reasonable to recommend screening, we suggest that sibling reflux may follow a more benign course.     

74例神经源性膀胱输尿管反流肾积水的治疗分析

目的总结对神经源性膀胱输尿管反流肾积水的治疗体会。方法回顾性分析74例神经源性膀胱肾积水患者的临床资料。针对不同情况采取不同的治疗方法：膀胱功能训练,膀胱内括约肌切开术,输尿管口交错固定术（改良Cohen cross-Trigonal法）。分析不同治疗方法的优缺点及适应证。结果 8例神经源性膀胱患儿行膀胱功能训练方法治疗,5例患儿的肾功能缓解或得到控制;经尿道膀胱内括约肌切开术治疗32例,22例患者的肾功能及肾积水情况得到较好的缓解或控制;选择输尿管口交错固定治疗者34例,31例患者的肾功能及肾积水情况得到较好的缓解或控制。结论针对不同的病例,3种治疗方法为有效及安全的。对儿童患者,膀胱功能训练是系统治疗的第一步;对尿道压力增高的患者,膀胱内括约肌切开术是有效的选择;对于尿道压力正常的患者,输尿管口交错固定术是安全有效的,成功率为91.2%（31/34）。     

Botulinum toxin type a injections into the trigone to treat idiopathic overactive bladder do not induce vesicoureteral reflux

PURPOSE: We assessed the generation of vesicoureteral reflux before and after injection of botulinum toxin A into the trigone of patients with nonneurogenic overactive bladder, and evaluated its short-term efficacy. MATERIALS AND METHODS: Adults with nonneurogenic overactive bladder resistant to behavioral treatments, pelvic floor exercises, medication and neuromodulation were included in the study. The initial evaluation (history, physical examination, 3-day urinary diary, V8 score, flowmetry and post-void residual) was repeated 6 weeks after botulinum toxin A injection. Videourodynamic study was performed 1 hour before injection and 6 weeks later. Botulinum toxin A (200 units) was injected into the detrusor in 10 sites over the bladder base including the trigone. The primary outcome was the presence or absence of vesicoureteral reflux before and 6 weeks after botulinum toxin A injection. The secondary outcomes were clinical and urodynamic parameter changes. Values were compared using the Wilcoxon test. RESULTS: A total of 12 women were enrolled in the study (median age 76 years). The duration of symptoms was 7.5 years. One patient was excluded from analysis because of a urinary tract infection. There were 10 women with no vesicoureteral reflux at baseline and 1 had bilateral vesicoureteral reflux (grade 2 right, grade 1 left). At 6 weeks there was no induced vesicoureteral reflux and the patient with vesicoureteral reflux at baseline showed no change in vesicoureteral reflux grade. No local or systemic side effects related to botulinum toxin A were reported. In terms of efficacy, at direct questioning 6 weeks after treatment 4 of 11 patients reported an improvement that made them ask for another injection. CONCLUSIONS: Botulinum toxin A injection into the trigone does not induce de novo vesicoureteral reflux in patients with nonneurogenic overactive bladder. The therapeutic value of this approach remains to be confirmed and compared to other injection designs.     

Efficacy and safety of oxybutynin in children with detrusor hyperreflexia secondary to neurogenic bladder dysfunction

PURPOSE: We evaluated the efficacy and safety of oxybutynin in children with detrusor hyperreflexia due to neurological conditions. MATERIALS AND METHODS: Study 1--A prospective, open label trial of 3 formulations of oxybutynin (tablets, syrup and extended release tablets) was conducted for 24 weeks in children 6 to 15 years old with detrusor hyperreflexia who used oxybutynin and clean intermittent catheterization. The effect of treatment on average urine volume per catheterization and on secondary urodynamic outcomes was evaluated. Study 2--The efficacy and safety of oxybutynin syrup were evaluated urodynamically in an open label study of children 1 to 5 years old with detrusor hyperreflexia who used oxybutynin and clean intermittent catheterization. RESULTS: Study 1--Mean urine volume per catheterization (+/- SEM) increased by 25.5 +/- 5.9 ml (p <0.001). Maximal cystometric capacity increased by 75.4 +/- 9.8 ml (p <0.001). Mean detrusor and intravesical pressures were significantly decreased by -9.2 +/- 2.3 (p < or =0.001) and -7.5 +/- 2.5 cm H2O (p <0.004), respectively, at week 24. Of 61 children with uninhibited detrusor contractions 15 cm H2O or greater at baseline 34 did not have them at week 24 (p <0.001). Improvements in bladder function were consistent across all oxybutynin formulations. Study 2--Mean maximal cystometric capacity increased significantly by 71.5 +/- 21.99 ml (p = 0.005). At study end only 12.5% of patients had uninhibited detrusor contractions 15 cm H2O or greater compared with 68.8% at baseline (p = 0.004). Oxybutynin was well tolerated in both studies. There were no serious treatment related adverse events. CONCLUSIONS: All 3 formulations of oxybutynin are safe and effective in children with neurogenic bladder dysfunction.     

Multivariate analysis of factors predicting success with dextranomer/hyaluronic acid injection for vesicoureteral reflux

PURPOSE: Factors influencing outcomes of dextranomer/hyaluronic acid injection for vesicoureteral reflux remain poorly defined. We performed multivariate analysis of the experience of 1 surgeon (WS). MATERIALS AND METHODS: The study group contained 168 patients and 259 refluxing units. Goal of injection was coaptation of the orifice with creation of a volcanic mound. Outcomes were determined by cystography obtained 12 weeks following injection. Intraoperative photographs of mounds were independently reviewed by 2 authors (WS, SY) without knowledge of results, and classified as "satisfactory" or "other." Univariate and multivariate logistic regression analysis was done evaluating influence of gender, age, voiding dysfunction, reflux grade, unilateral vs bilateral reflux, ureteral duplication, orifice laterality, subureteral vs intraureteral injection, volume injected and mound appearance. RESULTS: A single injection resolved reflux in 70% of patients and 78% of ureters. Additional injection resulted in overall success in 82% of patients and 86% of ureters. Multivariate analysis demonstrated that reflux grade, volume of dextranomer/hyaluronic acid injected and mound appearance correlated with outcomes. A satisfactory mound was achieved in 81% of ureters, of which 87% no longer refluxed. CONCLUSIONS: The ability to create a satisfactory mound was the most important factor determining success of dextranomer/hyaluronic acid injection. Increasing reflux grade was associated with a decreased likelihood of achieving a volcanic mound, and increasing volume injected suggested difficulty in creating a mound.     

A female case with Down syndrome and non-neurogenic neurogenic bladder

Although the prevalence of a learned voiding dysfunction and non-neurogenic neurogenic bladder (NNB), which is one type of dysfunctional elimination syndrome, is considered to be relatively rare, the association of NNB with Down syndrome (DS) has been elucidated in male patients. We herein describe the occurrence of NNB in an adult female with DS. The diagnosis was confirmed after completely ruling out any neurological or anatomical anomalies that could be related to a lower urinary tract dysfunction. She had renal dysfunction and multiple obstructive uropathies for which clean intermittent catheterization was successfully introduced.     

Cessation of prophylactic antibiotics for managing persistent vesicoureteral reflux

PURPOSE: We reviewed our experience with patients with vesicoureteral reflux treated off prophylactic antibiotics. MATERIALS AND METHODS: We retrospectively reviewed the records of patients with vesicoureteral reflux treated off prophylactic antibiotics, noting the intervals on and off antibiotics, urinary tract infection, signs and symptoms associated with urinary tract infection, and renal ultrasound and dimercapto-succinic acid scan findings. RESULTS: We identified 196 patients with vesicoureteral reflux treated off prophylactic antibiotics, including 122 who were infection-free while on and 124 who had no urinary tract infection while off prophylactic antibiotics. The infection rate on and off prophylactics was 0.29 and 0.24 urinary tract infections per patient per year, respectively. New scars were identified in 5 patients while on prophylactics and in 7 after antibiotics were discontinued. Comparing different subgroups off prophylactic antibiotics showed that children who presented with scarring had statistically fewer new scars than those with normal initial dimercapto-succinic acid imaging (p <0.043). Girls had significantly more urinary tract infections than boys while off prophylactics (p <0.01) despite the older age at antibiotic cessation. However, after infection occurred while off prophylactic antibiotics, new renal scars developed at about the same rate in boys and girls. Because most patients did not have a urinary tract infection while off prophylactic antibiotics, new renal scars developed in only 2.2% of all boys and 4% of all girls. CONCLUSIONS: Our findings imply that discontinuing antibiotics is reasonable and safe in patients in whom vesicoureteral reflux fails to resolve.     

Unsuspected meningocele presenting as neurogenic bladder dysfunction in an adult

Two adult patients with neurogenic bladder dysfunction secondary to unsuspected meningoceles are described. The implications of such problems and the need for complete neurourologic evaluation are important.     

Changing concepts concerning the management of vesicoureteral reflux

PURPOSE: Conservative estimates indicate that up to 54% of patients who present with vesicoureteral reflux have dysfunction voiding. Children with voiding dysfunction and vesicoureteral reflux historically have a high breakthrough infection rate of 34% to 43%. Breakthrough infection represents significant morbidity and it is the most common indication for surgical intervention for vesicoureteral reflux. Voiding dysfunction is present in 79% of patients who proceed to reflux surgery. We evaluated the impact of pelvic floor muscle retraining combined with a medical program in patients with voiding dysfunction and vesicoureteral reflux. MATERIALS AND METHODS: Children with a history consistent with voiding dysfunction and vesicoureteral reflux were screened by uroflowmetry/electromyography, bladder scan for post-void residual urine, renal ultrasound and voiding cystourethrography. Confirmed cases of voiding dysfunction and vesicoureteral reflux were prospectively enrolled in this study. Children participated in an interactive, computer assisted, pelvic floor muscle retraining program that involved a conservative medical regimen and pelvic floor muscle retraining. All patients received prophylactic antibiotics. We evaluated the rate of breakthrough urinary tract infection, reflux outcome and surgical intervention. A literature review with the key words vesicoureteral reflux, voiding dysfunction and urinary tract infection was performed to identify historical control cases for comparison. RESULTS: Study enrollment criteria were fulfilled by 49 girls and 4 boys 4 to 13 years old (average age 8.8), representing 72 units with low grades I to II (48) and high grades III to V (24) reflux. Mean followup was 24 months. Initial uroflowmetry/electromyography and bladder scan revealed a staccato flow pattern and normal post-void residual urine in 11% of cases, staccato flow pattern and elevated post-void residual urine in 10%, flattened flow pattern and normal post-void residual urine in 28%, and flattened flow pattern and elevated post-void residual urine in 51%. Breakthrough infection developed in 5 patients (10%), including 1 in whom reflux had resolved and 1 with grade I reflux who underwent observation. The parents of 2 patients elected to complete biofeedback without surgical intervention and these patients did not have a repeat infection. Reimplantation was performed in 1 case (2%). There was resolution in 18 low and 7 high grade refluxing units, including 2 older patients with a long history of high grade bilateral disease. Average time to resolution was 7.8 months. We noted elevated post-void residual urine in 88% of the patients with high grade reflux. Average age at resolution was 9.2 years. During a 24-month period one of us (P. H. M.) noted a greater than 90% decrease in surgical intervention. CONCLUSIONS: A combined conservative medical and computer game assisted pelvic floor muscle retraining program appears to have decreased the incidence of breakthrough urinary tract infections and facilitated reflux resolution in children with voiding dysfunction and vesicoureteral reflux. Patients with high grade reflux and voiding dysfunction commonly present with elevated post-void residual urine, contraindicating the indiscriminate administration of anticholinergics. Decreasing the rate of urinary tract infections may have a dramatic impact on the need for surgical intervention and enable the reflux resolution rate to approximate that in patients without voiding dysfunction. Prospective controlled trials are needed to determine whether pelvic floor muscle retraining combined with a conservative medical regimen alters the natural history of vesicoureteral reflux in patients with voiding dysfunction.     

A multivariate analysis of dysfunctional elimination syndrome, and its relationships with gender, urinary tract infection and vesicoureteral reflux in children

PURPOSE: We explored and quantified the relationships between dysfunctional elimination syndrome (DES), and gender, urinary tract infection (UTI) and vesicoureteral reflux (VUR) in children. MATERIALS AND METHODS: Data on 2,759 pediatric patients treated at a referral practice who underwent renal sonography and voiding cystourethrography were summarized. The patients were children with VUR or normal genitourinary anatomy who presented with UTI or dysfunctional voiding and children screened for genitourinary problems such as hematuria, sibling reflux or bedwetting. A multivariate logistic regression approach was used to model and quantify the associations between DES and other pediatric urology factors. RESULTS: Of the girls 36.0% with unilateral VUR had DES, while 36.1% with bilateral VUR had DES. The corresponding rates for boys were 20.5% and 21.2%. The higher rate of DES in girls was independent of UTI and VUR status. While UTI was not associated with DES in boys or girls without VUR, in patients with VUR and UTI the risk of DES almost doubled (OR 1.97). Reflux alone without UTI was negatively associated with DES in boys (OR 0.50, 95% CI 0.34, 0.73) and girls (OR 0.26, 95% CI 0.19, 0.36). CONCLUSIONS: Girls had a significantly higher rate of DES than boys in all UTI and VUR subgroups in the current data. UTI significantly impacts the DES occurrence in patients with VUR. No statistically significant difference was detected in the DES rate between the unilateral and bilateral VUR groups, and the reflux group as a whole did not seem to have a higher rate of DES in boys or girls.