Relationship between acute pyelonephritis, renal scarring, and vesicoureteral reflux

Acute pyelonephritis (APN) may produce permanent renal damage (PRD), which can subsequently lead to diverse complications. We prospectively evaluated 147 females and 122 males (mean age 3.5 years) with APN in order to analyze the relationship between the presence of PRD, at the time of cortical renal scintigraphy, and age, gender, episodes of urinary tract infection (UTI), and presence of vesicoureteral reflux (VUR). There were 152 children studied after the first proven UTI. VUR was present in 150 children. PRD was observed in 170 children. There were no significant differences between boys and girls. PRD was found in 36.4% of children younger than 1 year and in 70.1% of those older than 1 year (P<0.0001). Of children with VUR, 72% had PRD compared with 52% of children without VUR (P<0.0001). Of children with a first episode of UTI, 55.9% developed PRD as did 72.6% of those with recurrent UTI (P=0.004). Our results showed that PRD in children with APN is important, especially in the presence of VUR, recurrent UTI, and older age.     

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.     

The relationship between urinary tract infections and vesicoureteral reflux in Turkish children

Early determination of renal scar development risk in children following first urinary tract infection (UTI) and early detection and treatment of vesicoureteral reflux (VUR) are important to prevent renal functional impairment. The aim of this study was to determine the prevalence of VUR and associated renal scar formation, in children who had acute pyelonephritis (APN), first afebrile UTI, and recurrent afebrile UTIs. Patient records of 642 children having UTI were scrutinized and 278 out of 642 were enrolled in this study. The patients were divided into three groups: Group 1, patients with APN (n = 73); Group 2, patients with the first afebrile UTI (n = 88); and group 3, patients with recurrent afebrile UTIs (n = 117). Among these groups, VUR prevalence did not differ significantly (group 1: 24.6%, group 2: 22.7%, and group 3: 26.4%. Renal scarring was detected in 19.3% of the patients and was remarkably lower in group 2 when compared with the other two groups (P < 0.05). Renal scarring was found in 37.1% of the patients with VUR, whereas it was found in 14.3% of patients without VUR. Renal scarring incidence was remarkably higher in patients with grades 4–5 VUR (61.5%) compared with those with grades 1–3 VUR (30.6%) (P = 0.055). In conclusion, since VUR was demonstrated in as many as one-quarter of patients with the first afebrile UTI and VUR incidence did not differ significantly among the groups, all UTIs, lower and upper ones, should be carefully evaluated.     

Permanent renal parenchymal defects after febrile UTI are closely associated with vesicoureteric reflux

The finding of scintigraphic renal defects in children with febrile urinary tract infection (UTI) even in the absence of vesicoureteric reflux (VUR) has led to the conclusion that VUR is a weak predictor of renal defects in these patients. We used isotopic cystography (IC) for diagnosis of VUR in children with febrile UTI. Dimercaptosuccinic acid renal scintigraphy was performed 6 months after cure of the last UTI. Renal defects were defined by the finding of focal defects of radionuclide uptake and/or by a split renal function <43%. The study included 206 children with primary VUR and 77 without VUR. Among the subjects with and without VUR, respectively, renal defects were found in 40 and 6% (p=0.0001), focal uptake defects in 33 and 5% (p=0.0001) and split renal function <43% in 26 and 5% (p=0.0001). Permanent renal defects in children with febrile UTI are closely associated with VUR. The possibility that a child will have permanent renal defects can reasonably be ruled out on the basis of the absence of VUR by IC.     

Recurrence and follow-up after urinary tract infection under the age of 1 year

In order to analyze the risk factors for recurrence and the value of routine follow-up by monthly urine cultures in a group of children who had their first episode of urinary tract infection (UTI) under 1 year of age, we performed a retrospective survey of 262 children (134 girls, 128 boys) who were treated for their first UTI while aged under 1 year in the Department of Pediatrics, University of Oulu, during the years 1978–1984. Detailed data on these children concerning their first and recurrent UTIs were collected from hospital records using a formulated data sheet. Causative bacteria and vesicoureteral reflux (VUR) were analyzed as possible risk factors for recurrent UTI. The time of recurrence and the possible symptoms during the recurrent UTI were also investigated. The follow-up period after the first UTI was 3 years; 35% of the boys and 32% of the girls contracted a recurrent UTI during the 3-year follow-up. In 86% of cases, the first UTI recurrence occurred within 6 months of the primary UTI. Recurrent UTIs were detected significantly earlier with routine monthly follow-up compared with those seeking treatment because of symptoms (log rank test P<0.01). There was a significant difference in the number of recurrences of UTI according to the grade of VUR (P=0.006). Recurrence-free survival was shorter and recurrent UTIs occurred more often in the children with grade 3–5 VUR than in those with grade 0–2 VUR (log rank test P=0.0005). Children without VUR and children with grade 1–2 VUR did not differ in the recurrence rate, and thus grade 1–2 VUR did not increase the risk for recurrent UTI. Monthly routine urine cultures are efficient in detecting recurrent UTI infections in children. Since grade 3–5 VUR is a risk factor both for increased recurrence rate of UTI and for possible subsequent renal damage, these children should be followed with monthly urine cultures for UTI recurrences if not on preventive medication. Since the vast majority of UTI recurrences occur within 6 months of the first UTI, routine follow-up for 6 months seems to be sufficient after symptomatic UTI in children with grade 3–5 VUR. Received: 10 January 2000 / Revised: 21 August 2000 / Accepted: 21 August 2000     

Predictive value of clinical and laboratory variables for vesicoureteral reflux in children

We aimed to determine the predictability of clinical and laboratory variables for vesicoureteral reflux (VUR) in children with urinary tract infection (UTI). Data of children with febrile UTI who underwent voiding cystoureterography between 2002 and 2005 were evaluated retrospectively for clinical (age, gender, fever ≥38.5°C, recurrent UTI), laboratory [leukocytosis, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), pyuria, serum creatinine (S_Cr)] and imaging (renal ultrasonography) variables. Children with VUR (group 1) vs. no VUR (group 2) and children with high-grade (III–V) VUR (group 3) vs. no or low-grade (I–II) VUR (group 4) were compared. Among 88 patients (24 male), 38 had VUR and 21 high-grade VUR. Fever ≥38.5°C was associated with VUR [odds ratio (OR): 7.5]. CRP level of 50 mg/l was the best cut-off level for predicting high-grade VUR (OR 15.5; discriminative ability 0.89 ± 0.05). Performing voiding cystourethrography based on this CRP level would result in failure to notice 9% of patients with high-grade VUR, whereas 69% of children with no/low-grade VUR would be spared from this invasive test. In conclusion, fever ≥38°C and CRP >50 mg/l seem to be potentially useful clinical predictors of VUR and high-grade VUR, respectively, in pediatric patients with UTI. Further validation of these findings could limit unnecessary voiding cystourethrography.     

Vesicoureteric reflux in Kuwaiti children with first febrile urinary tract infection

The prevalence of vesicoureteric reflux (VUR) in children with urinary tract infection (UTI) varies among different racial groups. The purpose of this study was to determine the frequency of VUR and associated renal changes in a group of Arab Kuwaiti children with their first documented febrile UTI and to compare our findings with those reported from other racial groups. One hundred and seventy-four children (38 males and 136 females) fulfilled the study criteria and were divided into three age groups (<1 year, 1–5 years, and >5 years). Patients in each group had both micturating cystourethrography (MCUG) and 99m-Tc-dimercaptosuccinic acid (DMSA) renal scan after diagnosis. VUR was detected in 39 children (22%). Two-thirds of cases had mild reflux (grade I and II). Females (n=32) had more reflux than males (n=7) (24% vs. 18%). Sixty-three patients (36%) had abnormal (DMSA) renal scans (acute pyelonephritis [AP] or renal scars). Of these, 79% were children below 5 years. Abnormal DMSA scans were found in 4 of 38 males (11%) versus 59 of 136 females (43%). Abnormal scans in children with VUR were seen in 1 of 7 males (14%) versus 19 of 32 females (59%). In total, the combination of abnormal scan with VUR occurred in 1 of 38 males (3%) and in 19 of 136 females (14%), whereas abnormal scan without demonstrable VUR was seen in 3 of 38 males (8%) versus 40 of 136 females (29%). Our data showed that the frequency of VUR in Arab Kuwaiti children with febrile UTI is midway between Caucasian and other racial groups. In this study, males had a lower-risk profile than females, the latter having a higher rate of reflux as well as a higher rate of abnormal DMSA scans, irrespective of demonstrable VUR.     

Relationship between febrile urinary tract infection and urodynamics in myelodysplastic children with vesicoureteral reflux

OBJECTIVE: We conducted a retrospective study in order to identify factors that may predict the incidence of febrile urinary tract infection (UTI) in myelodysplastic children with vesicoureteral reflux (VUR). METHODS: A total of 23 myelodysplastic children with persistent VUR who were managed by clean intermittent catheterization (CIC) were eligible for this study. Any factors, including urodynamic parameters and urinary tract abnormalities, that may have been associated with the incidence of febrile UTI were evaluated using both univariate analysis and multiple logistic regression analysis. RESULTS: Of 23 patients, 10 (43%) had had one or more episodes of febrile UTI. Both univariate and multivariate analyses showed a statistically significant relationship between low bladder compliance (<10 ml/cm H(2)O) and episodes of febrile UTI. CONCLUSION: These results demonstrated that the urodynamics linked to bladder function disorder in the filling phase appear to be correlated with the incidence of febrile UTI in myelodysplastic children with VUR who are managed by CIC.     

Vesicoureteral reflux in children with suspected and proven urinary tract infection

The aim of this study was to estimate the prevalence of vesicoureteral reflux (VUR) and clinically significant ultrasonography (US) abnormalities in a large group of children with proven and suspected urinary tract infection (UTI). The medical reports on renal US and voiding cystouretrographies (VCUG) of 2,036 children were reviewed. Renal US was performed on all children and VCUG on 1,185 children (58%). Based on the urine culture data, the UTI diagnoses were classified into five reliability classes (proven, likely, unlikely, false and no microbial data). The UTI diagnose was considered proven in 583/2036 (28.6%) and false in 145 (7.1%) cases. The prevalence of VUR was similar among those with proven and false UTI [37.4 vs. 34.8%; relative risk (RR) 1.08, 95% confidence intervals (95% CI) 0.7–1.7, P = 0.75] and decreased with increasing age (P = 0.001). Clinically significant US abnormalities occurred in 87/583 (14.9%) cases with proven UTI and significantly less often (11/145, 7.6%) in the false UTI class (RR 1.96, 95% CI 1.1–3.6, P = 0.02). Our finding supports the claim that VUR is not significantly associated to UTI and that its occurrence among children even without UTI is significantly higher than traditional estimates. This challenges the recommendations of routine VCUG after UTI.     

Risk factors for renal scarring in children and adolescents with lower urinary tract dysfunction

Risk factors for renal scarring in children with lower urinary tract dysfunction (LUTD) were evaluated. The medical records of 120 patients were assessed concerning gender, presence of vesicoureteric reflux (VUR), bladder capacity, detrusor overactivity, residual urine, febrile urinary tract infection (UTI), bacteriuria, constipation, detrusor sphincter incoordination (DSI), high detrusor pressure at maximal cystometric capacity (PMCC), low compliance, and thickness and trabeculation of the bladder wall. Renal scarring was diagnosed by ^99mtechnetium-dimercaptosuccinic acid renal scan (DMSA). Renal scarring was detected in 38 patients (31%). VUR, UTI, decreased bladder capacity, urinary residue, and trabeculated and thick bladder wall were associated with scarring at univariate analysis. Multivariate analysis showed VUR (P < 0.0001) as the independent risk factor for renal scarring. Thickness of the bladder wall was a marginal risk factor (P  = 0.07). Although UTI was not a risk factor, it was associated with VUR (P  = 0.03). In our analysis, VUR was the main risk factor; however, renal scarring was probably due to multifactorial causes, as VUR was associated with UTI.     

Kidney imaging in management of delayed febrile urinary tract infection

We report a cross-sectional study performed to evaluate the imaging findings of 40 children, aged one month to five years (16.65 ± 14.97 months), who presented with protracted fever of more than 48 hours due to urinary tract infection (UTI). About 85% of the patients had positive Tc99-Dimercaptosuccinic acid (DMSA) scan and 58% had vesicoureteral reflux (VUR). Kidney sonography aided in the diagnosis and treatment in 10% of the patients. Age, sex, presence or laterality of VUR did not contribute to defective DMSA scan (pyelonephritis) (P > 0.05). Delayed diagnosis and treatment of febrile UTI is associated with a high incidence of positive findings of DMSA scan irrespective of age, sex or presence/absence of VUR. In mild VUR, the DMSA scan may be normal while in patients with moderate and severe VUR the DMSA scan is almost always abnormal. Thus, our study shows that a normal DMSA scan can help in ruling out moderate to severe forms of VUR and that cystography remains an excellent and standard tool for the diagnosis of VUR.     

Does pre-transplantation antireflux surgery eliminate post-renal transplantation pyelonephritis in children?

PURPOSE: Antireflux surgery for VUR before renal transplantation decreases the risk of post-kidney transplant UTI in pediatric patients with primary vesicoureteral reflux. We studied the risk of post-kidney transplant UTI in patients with or without surgical correction of VUR before transplantation compared to patients without VUR. MATERIALS AND METHODS: We compared 12 patients who had VUR corrected before transplantation (group 1) to 17 patients with VUR who did not undergo antireflux surgery before transplantation (group 2) and 36 patients undergoing renal transplantation without VUR (group 3). A total of 10 patients in group 1 (83.3%) and 10 in group 2 (58.8%) had high grade VUR. RESULTS: Eight patients in group 1 (66.7%), 6 in group 2 (35.3%) and 33 in group 3 (91.7%) remained free of febrile UTI during followup (p = 0.00). Among patients with high grade VUR 6 in group 1 and 1 in group 2 remained UTI-free (p = 0.02). A total of 33 patients in the control group (91.7%) remained free of febrile UTI, an incidence that was significantly lower compared to group 1 (p = 0.03) and group 2 (p = 0.00). Of the patients with high grade VUR 3 in group 1 (30%) and 4 in group 2 (40%) experienced recurrent febrile UTIs (p = 0.64). CONCLUSIONS: Even after surgical correction of VUR before transplantation the frequency of febrile UTI remained higher than that in kidney transplant recipients without VUR. In cases of high grade VUR reimplantation before renal transplantation decreased the rate of febrile UTI but it was still higher than the level of risk in the control group.     

Urinary incontinence in children with primary vesicoureteral reflux--urinary incontinence and function of refluxing kidney

The interrelation among urinary incontinence (nocturnal enuresis, urge incontinence), history of urinary tract infection and renal function was investigated in 153 children with primary vesicoureteral reflux who were more than three years old. Of them, 98 children (64%) had the chief complaint of urinary tract infection (UTI) and 43 children (28%), urinary incontinence. Of the children whose chief complaint was UTI, 44 (45%) had incontinence. Thus, 87 children (57%) with VUR had urinary incontinence. Almost all the children who had urinary incontinence and no previous UTI had good renal function. Renal dysfunction was found in children with previous UTI history. These studies on children with primary VUR more than three years old indicate that, although urinary incontinence could be a factor for recurrence of UTI and a probable cause of worsening of renal function, there is no direct correlation between urinary incontinence and renal dysfunction accompanied by VUR.     

Symptomatic urinary tract infections following voiding cystourethrography

The objective of this study was to assess the frequency of symptomatic urinary tract infections (UTIs) following voiding cystourethrography (VCUG) while using prophylactic antibiotics. Medical records of 421 patients who underwent a VCUG during a period of 4 years were reviewed. Three hundred forty-nine had a VCUG following a febrile UTI, and 72 had the test for evaluation of hydronephrosis. All received prophylactic antibiotics and were evaluated within 7–10 days following the VCUG. One hundred seventy-two children (41%) had an abnormal VCUG. Seven of 421 children (1.7%) had symptoms suggestive of UTI. Two had culture negative pyuria; one had Escherichia Coli UTI, and four had Pseudomonas aeruginosa UTI. On multivariate logistic regression analysis, the risk factors contributing to the development of UTI following VCUG were the presence of vesicoureteral reflux (VUR) and its severity (odds ratio [OR] 2.52; 95% confidence interval [CI] 2.24, 2.83, p =0.001; and OR 2.32; 95% CI 2.05,2.62, p =0.04, respectively). The incidence of VCUG-induced UTI in children receiving prophylactic antibiotic therapy is low. There is a relatively high rate of Pseudomonas UTI, especially in children with moderate to severe reflux. We recommend that children with symptoms suggesting a UTI following a VCUG should be treated for Pseudomonas aeruginosa pending culture results.     

Prevalence of hydronephrosis and vesicoureteral reflux in pediatric urinary tract infection

We studied 108 children diagnosed with urinary tract infection (UTI) to determine the frequency of hydronephrosis and vesicoureteral reflux (VUR). Fifty-two children (48.1%) had hydronephrosis (pyeloureteral junction obstruction: 27.8%) and 43 children (39.8%) had VUR (primary VUR: 36.1%). A renal scar was seen in 25.8% of the VUR cases. We recognized again that children with a history of UTI need to be examined promptly and thoroughly.     

Routine evaluation of vesico-ureteric reflux in children with anorectal malformation does not reduce the rate of urinary tract infection

ObjectiveChildren with anorectal malformations (ARM) have a high rate of renal anomalies and increased risk of urinary tract infection (UTI). We aimed to determine whether using routine Micturating Cystourethrogram (MCUG) to detect VUR is effective in reducing the incidence of UTI or renal scarring in children with ARM.MethodsA retrospective study of consecutive children diagnosed with ARM in two centres with a minimum of 3 years follow-up was performed, excluding those with cloaca or an MCUG prior to ARM repair. Univariate and multivariate logistic regression analysis was used to determine variables which were associated with VUR, UTI and renal scarring. Associations are described as Odd's Ratio (OR), 95% Confidence Interval. Significance was taken as p<0.05.Results344 children were included with a median age of 8 years (IQR 5–11 years). 150 (44%) were female. 89 (26%) had renal anomalies and 101 (29%) had spine anomalies. 148 patients had routine MCUG and VUR was found in 62 (42%) of these children. Univariate analysis did not correlate any of the assessed variables with VUR or renal scarring. However, abnormal renal ultrasound - OR 6.18 (95% CI 2.99–13.07, p 0.0001) was associated with UTI whilst abnormal spine - OR 0.27 (95% CI 0.10–0.62, p 0.009), low ARM - OR 0.30 (CI 0.14–0.63, p 0.006) and intermediate ARM - OR 0.35 (CI 0.17–0.70, p 0.01) were associated with a reduced risk of UTI. On multivariate analysis, only abnormal renal USS retained a significant association with UTI (p<0.0001).ConclusionsVUR is common in patients with ARM. Children with an abnormal R-USS are at increased risk of UTI. Performing routine MCUG does not reduce the risk of UTI in children with ARM.     

Vesicoureteral reflux and reflux nephropathy

Primary vesicoureteral reflux (VUR) is the commonest congenital urological abnormality in children, which has been associated with an increased risk of urinary tract infection (UTI) and renal scarring, also called reflux nephropathy (RN). In children, RN is diagnosed mostly after UTI (acquired RN) or during follow-up for antenatally diagnosed hydronephrosis with no prior UTI (congenital RN). The acquired RN is more common in female children, whereas the congenital RN is more common in male children. This observation in children might help explain the differences in the clinical presentation of RN in adults, with males presenting mostly with hypertension, proteinuria, and progressive renal failure as compared with females who present mostly with recurrent UTI and have a better outcome. Known risk factors for RN include the severity of VUR, recurrent UTI, and bladder-bowel dysfunction; younger age and delay in treatment of UTI are believed to be other risk factors. Management of VUR is controversial and includes antimicrobial prophylaxis, surgical intervention, or surveillance only. No evidence-based guidelines exist for appropriate follow-up of patients with RN.     

Febrile urinary tract infection in children: ampicillin and trimethoprim insufficient as empirical mono-therapy

The aim of this study was to characterize the pathogens and their antibiotic susceptibilities in defined groups of children (total number 694) with urinary tract infection (UTI) regarding age, first UTI (FUTI) or recurrent UTI (RUTI), renal abnormalities or vesico-ureteric reflux (VUR) in order to optimize empirical antibiotic therapy and prophylaxis. In patients aged between 1 month and 24 months with a first febrile UTI (FUTI; n = 205) the leading pathogen was Escherichia coli (E. coli) (83.4%). In comparison with patients with FUTI, those with RUTI (n = 24) had more Enterococcus and Enterobacter infections and higher resistance rates of E. coli against trimethoprim (TMP), trimethoprim/sulfamethoxazole (SXT) or ampicillin (AMP). Boys with ultrasound-detected renal abnormalities (n = 71) showed 14.2% Pseudomonas and 59.1% E. coli infections versus girls (n = 48) (2.1% Pseudomonas and 93.7% E. coli). Of 390 patients who underwent voiding cysto-urethrography, 31.5% had VUR. Of them, 45.5% received antimicrobial prophylaxis with SXT (n = 30) or cefazolin (n = 26). There was no difference between girls (n = 242) and boys (n = 148) regarding the frequency of VUR and pathogens. There were more TMP- and SXT-resistant E. coli cultures from patients with VUR (37.8%) than from those without VUR (25.8%). Treatment with TMP, SXT and AMP alone appeared to be insufficient in many cases because of high resistance rates of E. coli and other uropathogens.     

Acute pyelonephritis and sequelae of renal scar in pediatric first febrile urinary tract infection

To investigate the incidence of acute pyelonephritis (APN) and renal scarring in children with febrile urinary tract infection (UTI), 191 of 216 (88%) children with their first episode of UTI received (99m)Tc-dimercaptosuccinic acid renal single-photon emission computed tomography. They were investigated within 7 days of admission and were followed for 6 months. One hundred and six patients (49.1%) underwent a voiding cystourethrogram. The incidence of vesicoureteric reflux (VUR) in group I (相似文献   

Probiotics prophylaxis in children with persistent primary vesicoureteral reflux

Probiotics, beneficial living microorganisms, have been proven to be effective in preventing gastrointestinal infections, but their effect in preventing urinary tract infection (UTI) is inconclusive. A prospective randomized controlled study was done to compare the preventive effect of probiotics with conventional antibiotics in children with persistent primary vesicoureteral reflux (VUR). One hundred twenty children who had had persistent primary VUR after antibiotic prophylaxis for 1 year were randomly allocated into a probiotics (Lactobacillus acidophilus 10⁸ CFU/g 1 g b.i.d., n = 60) or an antibiotics (trimethoprim/sulfamethoxazole 2/10 mg/kg h.s., n = 60) prophylaxis group during the second year of follow-up. The incidence of recurrent UTI was 18.3% (11/60) in the probiotics group, which was not different from 21.6%(13/60) in the antibiotic group (P = 0.926). The causative organisms of recurrent UTI were not significantly different between the two groups (P = 0.938). Even after stratification by VUR grade, age, gender, phimosis, voiding dysfunction and renal scar, the incidence of recurrent UTI did not differ significantly between the two groups (P > 0.05). The development of new renal scar was not significantly different between the two groups (P > 0.05). In conclusion, probiotics prophylaxis was as effective as antibiotic prophylaxis in children with persistent primary VUR.