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BackgroundAn association between bladder-bowel dysfunction (BBD) and urinary tract infection (UTI) is well-known. However, a question less explored is whether children with UTI early in life also have increased prevalence of BBD after they are toilet-trained. In this study, consecutively selected children with pyelonephritis during their first year of life were assessed for BBD at pre-school age.MethodsNinety-two children (51 boys) hospitalized due to pyelonephritis during their first year of life were assessed for BBD at median age 5.4 years. A validated BBD questionnaire, along with urine flow and residual volume measurements, was used for diagnosing BBD. During follow-up, the group was well-characterized regarding renal status, vesicoureteral reflux (VUR), and recurrent UTI.ResultsBBD was diagnosed in 35/92 (38%), of which the majority was sub-diagnosed with dysfunctional voiding (DV). There was a strong association between BBD and recurrent UTI during follow-up (p p = 0.0008). BBD was also associated with kidney damage (p = 0.017).ConclusionIn children with pyelonephritis during the first year of life, 38% had BBD at pre-school age, regardless of whether they had VUR or not. The study shows an important association between BBD and recurrent UTI, so an assessment of BBD is therefore recommended for pre-school children with UTI, especially when they have history of pyelonephritis during infancy.

AIM Aim of the study was to provide a scoring system for predicting downgrading and resolution of infantile high-grade vesicoureteral reflux (VUR). METHODS Eighty-nine infants (65 boys) with high-grade VUR (grade 4-5) diagnosed at median age 2.5 months and followed to 39 months had repeated investigations of VUR grade, renal damage/function and bladder function. Recurrent urinary tract infections (UTIs) were registered. Risk variables collected at 1 year were analysed as independent factors for spontaneous resolution to grades ≤2 and 0, using univariable/multivariable logistic regression. RESULTS A scoring system was built with a total of 14 points from four independent risk factors (sex, breakthrough UTI, type of renal damage and subnormal glomerular filtration rate). Children with persistent VUR (grade 3-5) had higher scores compared with the group with spontaneous resolution (grade 0-2) (mean 7.9 vs. 4.5, P

Thank you for your commentary1 on the clinical usefulness of our scoring system2 . We do agree about the importance of patient selection and individualized risk-benefit approach for the management of high-grade vesicoureteral reflux (hVUR) in general and infant hVUR in particular.

Introduction High-grade vesicoureteral reflux (VUR) in children is associated with recurrent urinary tract infection (UTI) and renal damage. Breakthrough UTI despite continuous antibiotic prophylaxis (CAP) during the first years of life is a matter of concern and evokes early intervention. We investigated whether early endoscopic treatment (ET) of VUR grade 4–5 can reduce the risk of UTI recurrence and renal scarring. Materials and methods This prospective, randomized, controlled, multicentre, 1-year follow-up trial comprised 77 infants

AIM In approximately one third of cases, congenital high-grade vesicoureteral reflux (VUR) diagnosed during infancy is seen together with lower urinary tract dysfunction (LUTD), characterised by a high-capacity bladder and incomplete emptying. In an earlier study, 20 of these infants were treated with clean intermittent catheterisation during a 3-year period and with surgical treatment of the VUR before catheterisation was ended. In the present study, bladder function was evaluated in these children at school age. METHODS Bladder function was evaluated in the 20 children at a mean age of 7.3 years using a validated voiding-bowel questionnaire with scores (cut-off score 7) and a urine flow/residual study. RESULTS Four children (20%) had a normal voiding function at follow-up, whereas 11 (55%) had a clear bladder/bowel dysfunction (scores 7-19) and five (25%) had a mild dysfunction (score 6). Ten (63%) of the children with any dysfunction were recognised as dysfunctional voiding. Recurrent febrile urinary tract infections were correlated with the scores of faecal questions (P = .041), but for total scores P = .058. CONCLUSION The follow-up of bladder function in children at 7.3 years, diagnosed with high-grade VUR and LUTD in infancy, revealed bladder/bowel dysfunction of varying severity in the majority of cases.

Purpose: We studied the inheritance pattern, clinical features and outcome in children with vesicoureteral reflux (VUR). Characteristics of known familial VUR cases were also compared with those of sporadic VUR. Material and Methods: 726 patients were treated for VUR between 1990-2004. The families were contacted by letter inquiring if other members of the family were affected. The phenotype of all cases (familial and non-familial) was characterized in terms of presenting symptoms, reflux grade, recurrent urinary tract infections, kidney damage, and the natural course of reflux. Results: The response rate was 79%. A total of 99 individuals (22%) reported relatives with VUR. Since some of the 99 index cases belonged to the same family, the total number of families was ultimately 66. The distribution of relatives with VUR was: 38 siblings, 20 parents (15 mothers), 19 cousins, 15 aunts/uncles and 12 grandparents. The phenotype of VUR did not differ between familial and non-familial cases. However, VUR among relatives was of milder grade than index and sporadic cases. Conclusions: The proportion of hereditary reflux in our material was lower than in other studies (22%). We found a strong overrepresentation of maternal transmission of reflux. Severity of the disease did not differ between familial and non-familial VUR.

Summary Introduction It has been suggested that infants with high-grade vesicoureteral reflux (VUR) have lower urinary tract dysfunction (LUTD) that is characterised by large bladder capacity (BC) and increased post-void residual (PVR). However, most of these infants have normal or small BC in early infancy and develop large capacity during the first year of life. Objective This study aimed to see whether LUTD development during the infant years in children with high-grade VUR could be prevented by early reflux resolution. Materials and methods For early VUR intervention, endoscopic treatment (ET) was used in a randomised trial comprising 77 infants (55 boys) aged Results There were no differences in bladder function variables seen between the treatment groups, despite significant differences in VUR resolution. Analysing bladder function related to VUR outcome (VUR grade ≤2 vs grade >2), independent of treatment, showed that VUR grade ≤2 was associated with a smaller BC at 1 year ( P = 0.050) (a tendency already seen at baseline) and a lower PVR at baseline ( P = 0.010). PVR increased from baseline to 1 year ( P = 0.037) in children with grade ≤2 VUR (Summary Table). The group with persistent bilateral grade 5 VUR at 1 year had more abnormal bladder variables compared with other study subjects, with a tendency of larger BC ( P = 0.057), higher PVR ( P = 0.0073) and more LUTD ( P = 0.029) at baseline and a larger BC at 1 year ( P = 0.016). In explanatory analyses, using logistic regression, a high PVR at baseline was identified as a predictor of VUR grade >2 ( P = 0.046), persistent bilateral grade 5 VUR ( P = 0.022), recurrent urinary tract infection ( P = 0.034), and only a tendency was seen regarding new renal damage ( P = 0.053). Conclusion There was no between-group difference seen in bladder function. In children with VUR resolution at follow-up, independent of treatment, BC decreased, whereas PVR increased. High PVR at baseline was a predictive factor for both non-resolution of high-grade VUR and recurrent urinary tract infection. The results suggest that LUTD cannot be prevented by early VUR resolution, but rather is an important prognostic factor for VUR outcome in both endoscopic and prophylactic treatment. Summary Table . Bladder variables by grade ≤2 vs grade >2 VUR at 1-year follow-up. Variable Total (n = 74) Within-group P -value Grade ≤2 VUR at 1 year (n = 29) Grade >2 VUR at 1 year (n = 45) Between-group P -value Bladder capacity (%) • Baseline 126 (49–466) 120 (49–283) 138 (65–466) 0.14 • 1 year 113 (3–296) 0.075 90 (31–194) 121 (30–296) 0.050 • Large (≥150%) baseline 28 (41%) 7 (27%) 21 (49%) 0.12 • Large (≥150%) 1 year 22 (33%) 7 (26%) 15 (39%) 0.43 Residual urine (ml) • Baseline 9 (0–83) 6 (0–55) 11 (1–83) 0.010 • 1 year 14 (0–108) 0.025 9 (0–84) 16 (0–108) 0.41 Lower urinary tract dysfunction • Baseline 17 (24%) 3 (12%) 14 (33%) 0.087 • 1-year follow-up 18 (27%) 6 (22%) 12 (31%) 0.63 Continuous variables: median (minimum−maximum), categorical variables: n (%).

Summary Introduction High-grade vesicoureteral reflux (VUR) in infants is associated with congenital renal abnormalities, recurrent UTI, and bladder dysfunction. Endoscopic treatment (ET) is a well-established method in children with low to moderate reflux grades, but there is a lack of randomised controlled trials regarding the use of ET versus continuous antibiotic prophylaxis in infants with high-grade VUR. Objective This study aimed to determine whether high-grade VUR in infants can be treated with endoscopic injection and whether ET is superior to antibiotic prophylaxis in the treatment of VUR. Materials and methods This prospective, randomised, controlled, multicentre, 1-year follow-up trial comprised 77 infants (55 boys, 22 girls) n = 30/ n = 47). Of the infants, 52 (68%) had bilateral VUR. Thirty-nine were randomised to antibiotic prophylaxis and 38 to ET (with prophylaxis until resolution). Voiding cystourethrogram, ultrasound, renal scintigraphy, and free voiding observation were performed at study entry and after 1 year to evaluate VUR grade, and renal and bladder function. Results VUR grade ≤2 was seen in 22 (59%) infants in the endoscopy group and eight (21%) in the prophylaxis group at follow-up ( p = 0.0014). The success rate in the endoscopy group was 100% in unilateral grade 4, falling to 31% in bilateral grade 5 ( p = 0.0094). Correspondingly, the results in the prophylaxis group were 40% in grade 4 down to 0% in bilateral grade 5 ( p = 0.037) ( Table ). Logistic regression analyses identified ET, VUR grade 4, unilaterality, and low residual urine at baseline as positive predictors of VUR down-grading to ≤2 (area under ROC curve 0.88). In four patients with reflux resolution after one injection, dilating reflux recurred at the 1-year follow-up. One patient had a UTI possibly related to ET. In our material four patients required re-implantation, of whom one was obstructive after injection. Discussion The opportunity to offer even small infants with high-grade VUR an alternative, minimally invasive treatment option is a great advance in paediatric urology. In this high-risk group, bilateral VUR grade 5 stands out with its poor bladder function and low chance of resolution. The recurrence rate of dilating VUR after successful ET is consistent with previous studies. The limitations are the relatively small number of patients and the short follow-up. Conclusion High-grade VUR in infants can be treated with injection therapy and the resolution rate is higher than that of prophylaxis treatment. The complication rate is low and VUR grade 4, unilaterality, and low residual urine are favourable for the resolution and down-grading of VUR. Table . VUR-grade at 1-year follow-up and VUR ≤2 divided by VUR-grade and uni- or bilaterality at baseline trial. Variable Endoscopy group ( n = 38) Prophylaxis group ( n = 39) p -value Grade of VUR at 1-year follow-up VUR = 0 17 (46%) 6 (16%) VUR = 1 2 (5%) 0 (0%) VUR = 2 3 (8%) 2 (5%) VUR = 3 6 (16%) 7 (18%) VUR = 4 4 (11%) 13 (34%) VUR = 5 5 (14%) 10 (26%) 0.0007 VUR grade ≤2 vs >2 at 1-year follow-up VUR grade 0–2 22 (59%) 8 (21%) VUR grade 3–5 15 (41%) 30 (79%) 0.0014 Variable Endoscopy group Prophylaxis group VUR grade ≤2 at 1-year follow-up ( n = 22) VUR grade >2 at 1-year follow-up ( n = 15) p -value VUR grade ≤2 at 1-year follow-up ( n = 8) VUR grade >2 at 1-year follow-up ( n = 30) p -value VUR grade at Baseline Unilateral 4 7 (100%) 0 (0%) 2 (40%) 3 (60%) Bilateral 4 6 (75%) 2 (25%) 4 (40%) 6 (60%) Unilateral 5 4 (67%) 2 (33%) 2 (29%) 5 (71%) Bilateral 5 5 (31%) 11 (69%) 0.0094 0 (0%) 16 (100%) 0.037

We studied variables with impact on cessation of congenital high grade vesicoureteral reflux in univariate analyses and provide a multivariate model for prediction of reflux resolution.A total of 80 male and 35 female infants (median age 2.7 months) were included in this prospective observational study. Of the cases 71% were diagnosed after urinary tract infection and 26% after prenatal ultrasound. Reflux was bilateral in 70% of the patients and maximum grade was III in 16%, IV in 45% and V in 39%. The study protocol included repeat videocystometries, renal scintigrams, chromium edetic acid clearances and free voiding observations. Median followup was 36 months.Overall spontaneous reflux resolution, including cases downgraded to grade I to II, was 38%. Variables significantly negatively correlated to resolution were breakthrough febrile urinary tract infection, bladder dysfunction, higher grade of reflux at inclusion, renal abnormality, subnormal renal function, increased bladder capacity, residual urine and passive occurrence of reflux. Multivariate Cox proportional hazard model with stepwise selection identified 3 independent predictors--renal abnormality (hazard ratio 0.45, 95% CI 0.31-0.64, p0.0001), bladder dysfunction (hazard ratio 0.43, 95% CI 0.29-0.64, p0.0001) and breakthrough urinary tract infection (hazard ratio 0.38, 95% CI 0.18-0.78, p = 0.009). Performance of the model was evaluated by the receiver operating characteristic curve, with a calculated area under the curve of 83%.Overall resolution rate in congenital high grade vesicoureteral reflux is high during the first years of life. By multivariate analyses renal abnormality, bladder dysfunction and breakthrough febrile urinary tract infection were identified as strong independent negative predictive factors for reflux resolution.

Purpose To investigate whether mode of occurrence of vesicoureteral reflux (VUR), during micturition (M), during filling without increase in pressure (passive, P) or in response to an overactive contraction (OA), can be explained by differences in bladder function. Also, to study if the mode of occurrence of VUR can predict spontaneous resolution. Materials and methods There were 93 infants (68 boys and 25 girls) with VUR (grade III–V) included. Videocystometry was performed at median ages 5, 22 and 32 months registering grade and mode of reflux and bladder function characteristics. Results Mode of occurrence of reflux changed with age. During infancy P, OA and M reflux comprised almost equal parts. At follow up, P reflux had increased and both OA and M reflux had decreased. This was partly due to a significantly higher probability of spontaneous resolution for M than P reflux, at 40 months (42 vs 18%). P and M reflux were significantly correlated to bladder function characteristics. P reflux was seen in children with high bladder capacity and occurred early in filling. Other predictors were higher age within the respective group and female sex. M reflux was correlated to lack of residual urine, low bladder capacity and absence of overactivity. Other indicators were male sex and low-grade reflux. Conclusions P and M reflux correlate to different bladder patterns: P with high bladder capacity and M with low bladder capacity and without signs of bladder dysfunction. M seems to be benign with a higher resolution rate.

We sought to study renal abnormality and renal function through time in infants with high grade vesicoureteral reflux.This prospective observational study included 115 infants (80 boys and 35 girls) younger than 1 year with grade III to V vesicoureteral reflux. The diagnosis was made after prenatal ultrasound in 26% of the patients and after urinary tract infection in 71%. Patients were followed by renal scintigraphy, 51chromium edetic acid clearance and video cystometry. Median followup was 62 months.Renal abnormality, which was found in 90% of the children at followup, was generalized in 71% and focal in 29%. The abnormality was bilateral in 28% of the affected patients. Total glomerular filtration rate was less than 80% of expected in 30% of the patients. Single kidney function was less than 40% of expected total glomerular filtration rate in 71% of the patients. Renal status (parenchymal abnormality and function) remained unchanged through time in 84 of 108 available cases (78%), improved in 5 (5%) and deteriorated in 19 (18%). Predictive factors for deterioration were recurrent febrile urinary tract infection, bilateral abnormality and reduced total glomerular filtration rate. Deteriorated renal status was more common in cases diagnosed prenatally than in those detected after urinary tract infection.Among these infants with high grade vesicoureteral reflux renal abnormality was frequent and was associated with subnormal filtration of one of the kidneys. Decreased total glomerular filtration rate was seen in about a third of the patients. Overall deterioration of renal status was seen in only a fifth of the patients. Infection control seems to be an important factor to minimize the risk.

We investigated whether the treatment of bladder dysfunction in infants with congenital high grade vesicoureteral reflux could influence the spontaneous resolution rate of the reflux and the number of recurrent urinary tract infections.A total of 115 infants with high grade vesicoureteral reflux were included in a followup study of bladder function and reflux resolution between 1993 and 1999. The present study deals with 20 of these infants with mainly grade V reflux, most of whom had recurrent urinary tract infections in combination with high post-void residual and high bladder capacity. Treatment with clean intermittent catheterization was instituted during infancy in these 20 patients and continued until a median age of 4 years.Bladder capacity was high at presentation and at all followup investigations in the clean intermittent catheterization treated group. Moreover, residual urine was high at presentation and especially between ages 1 and 2 years. However, after bladder control was achieved this residual decreased and consisted mainly of reflux urine. In only 1 girl did reflux resolve spontaneously during the 4-year followup period. A total of 18 patients were treated surgically at the end of this period, and clean intermittent catheterization could be stopped a few months later in all but 2. Urinary tract infection recurrences were uncommon after the institution of treatment.The treatment of bladder dysfunction characterized by a high capacity bladder with poor emptying in infants with congenital high grade reflux does not influence the rate of spontaneous resolution. On the other hand, the tendency toward recurrent urinary tract infections appears to decrease with treatment.

Reports concerning bladder dysfunction patterns in infants with high grade vesicoureteral reflux during the first year of life vs older children with reflux are contradictory. To describe the development of bladder function characteristics in children with congenital dilating reflux, we evaluated such infants urodynamically and followed them regularly for a 3-year period.A total of 89 males and 25 females with grade III to V dilating reflux were evaluated 3 times using videocystometry at mean ages of 6, 20 and 40 months.Characteristics of the urodynamic pattern at 6 months could not be differentiated from normal patterns for that age, including low and normal bladder capacity, high voiding pressure levels, dyscoordination at voiding (80%) and overactivity during filling (60%). However, at 20 months the overall pattern was different, including increased bladder capacity and residual volume, normal voiding pressure, persistent overactivity during filling and dyscoordination at voiding. Bladder dysfunction was seen in 48 children (42%) at 20 months, of whom 34 primarily had high bladder capacity with incomplete emptying (dilated bladder dysfunction) and 14 had overactive bladder. Predictors for development of dilated bladder dysfunction at followup were high residual urine at 6-month examination and recurrent urinary tract infections. Recurrent infections were significantly correlated to high residual urine at all investigations and to detrusor overactivity at the 20-month examination.Urodynamic patterns changed between the first and second year of life in patients with dilating reflux, from an immature pattern with high pressure levels to high capacity bladder with incomplete voiding. Therefore, bladder dysfunction, which was seen in 42% of patients, was only possible to diagnose after the first year of life and was mainly seen as high capacity bladder with incomplete voiding.

Summary Objectives It has been suggested that infants with dilating vesicoureteral reflux (VUR) often have lower urinary tract (LUT) dysfunction. Signs such as high voiding pressure levels, low bladder capacity and dyscoordination at voiding have previously been thought to be indicative of dysfunction. However, these findings have also been recognised in healthy infants and are, thus, not specific to dysfunction in this age group. The urodynamic findings of interest for LUT dysfunction in children with high-grade VUR have been shown to be high bladder capacity with incomplete emptying, and often with overactivity during filling. Because the bladders in children with VUR are often only investigated with voiding cystourethrography (VCUG) and not urodynamics, the question has arisen as to whether some of the urodynamic findings indicating dysfunction can be recognised as radiological signs. The aim of the present study was to evaluate whether cystometric signs of LUT dysfunction in infants with high-grade VUR could be recognised in VCUG. Materials and methods One hundred and fifteen infants (80 boys) with Grades III–V VUR were included and investigated repeatedly with videocystometry (VCM) at a median age 6, 21 and 39 months. The sign looked for in the VCUG was bladder size (large, normal or small), according to the chosen levels in the bony pelvis. To validate the chosen levels for the different bladder sizes, bladder capacity data from a longitudinal study in healthy children were used. In addition, abnormalities in bladder wall/form and filling of the posterior urethra without voiding, as signs of bladder overactivity and detrusor–sphincter dyscoordination, were evaluated. Results Bladder size was estimated on VCUG as large, normal or small, according to pelvic landmarks. Large bladder size was mainly seen at the second and third evaluations (64% and 46%), whereas small capacity was mainly seen during the first year (33%). Corresponding cystometric capacities (ml) showed a significant difference between the groups of small, normal and large bladder size. The cystometric capacities of large and small bladder size were also compared with bladder capacity in healthy controls, where large had significantly higher bladder capacity versus age (P = 0.0001) and small had significantly lower (P = 0.011) bladder capacity versus age than in the healthy controls. Bladder shape/wall pathology was mainly seen during the first year (42%), combined with small capacity, and correlated to overactive contractions during filling. Moreover, filling of the posterior urethra without voiding, indicating detrusor/sphincter dyscoordination at voiding, was quite common during the first year (33%), and then successively decreased. Conclusions The clinical implication from this study of small children with high-grade VUR was that a large bladder on VCUG was synonymous with a high-capacity bladder. According to earlier studies, this is a sign of LUT dysfunction in this age group and should therefore be an indicator for additional studies of bladder function. Overactive contractions could also be recognised in VCUG, but only at the infant evaluation, which should also be regarded as an indicator of LUT dysfunction. All other bladder VCUG signs mainly seen during early infancy were signs of immature bladder function and not a result of VUR dysfunction.

Purpose The aim of the study was to investigate if bladder function variables could be recognized as radiological signs in the VCUG in children with vesicoureteral reflux (VUR). Material and Methods 116 patients with high-grade VUR had videocystometry at median age 6, 21 and 39 months. X-ray films of the bladder was reviewed for size (big = above the line between the iliac crests, small = below the line between the lower ends of sacroiliac junctions), pathology of the bladder wall (irregular, trabeculated, diverticula) and pathology of the bladder neck / proximal urethra (urethral sphincter closed with filling of the posterior urethra - PUF). Results Bladder volume estimated from the X-ray films (big, normal, small), correlated well to bladder volumes obtained from the urodynamic investigations, with significant difference between the groups (p Low age ( Conclusions Our observations indicate that bladder capacity could roughly be estimated from x-ray films by using the landmarks suggested in this study. The typical urodynamic pattern for small infants: low bladder capacity, overactivity, high voiding pressure and dyscoordination at voiding was recognised in X-ray films from VCUG.

Purpose The aim was to identify prognostic factors for spontaneous resolution of congenital high-grade vesicoureteral reflux (VUR). Material and Methods 115 infants (85 boys and 35 girls) were included at median age 2.7 months. 74% were diagnosed after urinary tract infection (UTI) and 26% after prenatal ultrasound. VUR was bilateral in 70% and of maximum grade III in 15%, grade IV in 45% and grade V in 40%. All have been followed with repeated video-VUCG, renal scintigrams (MAG-3 and DMSA) and 51Cr-EDTA-Clearances. Median follow-up time was 36 months. Results The overall spontaneous resolution rate (to grade II or less) was 39%. Significantly lower resolution was found in univariate Cox analysis, illustrated in Kaplan Meier survival curves, in those with renal damage, breakthrough UTI, bladder dysfunction, high bladder capacity, impaired renal function (lowered GFR), and reflux occurring without increase in pressure early during filling. Voiding reflux was connected to a high rate of spontaneous resolution. The resolution rate was also directly related to grade of VUR. There was no significant difference in resolution rate between boys and girls, pre or postnatal diagnosis, uni or bilateral VUR at start. Conclusions The overall resolution rate in congenital high-grade vesicoureteral reflux was high during the first years of life. A number of factors have been identified as important in the prediction of the long-time outcome of VUR in this study. Of these factors renal damage, bladder dysfunction and recurrent UTI have been shown to be the strongest independent predictors in a stepwise multivariate Cox analysis.