Urine neutrophil gelatinase-associated lipocalin and other biomarkers in infants with urinary tract infection and in febrile controls.

BACKGROUND: Urine biomarkers are commonly used in the evaluation of acute kidney injury, and are gaining attention as tools for studying urinary tract infections (UTIs). We analyzed neutrophil gelatinase-associated lipocalin (NGAL) and seven other urine biomarkers to evaluate their usefulness in the diagnosis of UTI in infants. METHODS: Eight urine biomarkers were analyzed in 108 infants with UTI. Controls were 64 febrile children without UTI and 13 healthy children. Logistic regression and construction of receiver operating characteristic (ROC) curves were performed for UTI patients versus febrile controls for all biomarkers. RESULTS: The best biomarkers to differentiate between UTI and febrile controls were NGAL and interleukin 8 (IL8). Urine NGAL in absolute concentration and adjusted for creatinine had a sensitivity of 93% and 96% and a specificity of 95% and 100% for diagnosing UTI, with a cut-off concentration of 38 ng/mL and 233 ng/mg respectively. CONCLUSIONS: Urine biomarkers, particularly NGAL, can aid in the diagnosis of UTI among febrile infants. The results suggest that in infants with fever and high NGAL, UTI is most likely, whereas in infants with fever and low NGAL, other causes of fever should be looked for.

Urinary tract infection in small children: the evolution of renal damage over time.

BACKGROUND: Our objective was to analyze the evolution of kidney damage over time in small children with urinary tract infection (UTI) and factors associated with progression of renal damage. METHODS: From a cohort of 1003 children <2 years of age with first-time UTI, a retrospective analysis of 103 children was done. Children were selected because of renal damage at index 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy at least 3 months after UTI, and a late DMSA scan was performed after at least 2 years. Damage was classified as progression when there was a decline in differential renal function (DRF) by ≥4%, as regression when there was complete or partial resolution of uptake defects. RESULTS: Of 103 children, 20 showed progression, 20 regression, and 63 remained unchanged. There were no differences between groups regarding gender or age. In the progression group, 16/20 (80%) children had vesicoureteral reflux (VUR) grade III-V and 13 (65%) had recurrent UTI. In multivariable regression analysis, both VUR grade III-V and recurrent UTI were associated with progression. In the regression group, 16/20 (80%) had no VUR or grade I-II, and two (10%) had recurrent UTI. CONCLUSIONS: Most small children with febrile UTI do not develop renal damage and if they do the majority remain unchanged or regress over time. However, up to one-fifth of children with renal damage diagnosed after UTI are at risk of renal deterioration. These children are characterized by the presence of VUR grades III-V and recurrent febrile UTI and may benefit from follow-up.

Obstetrical outcome in women with urinary tract infections in childhood.

INTRODUCTION: Urinary tract infections (UTI) during childhood can result in permanent renal damage, with possible implications for future pregnancies. The aim of this prospective study was to investigate pregnancy outcomes in women followed after their first UTI in childhood. MATERIAL AND METHODS: A cohort of 72 parous women was followed from their first UTI in childhood up to a median age of 41 years. Clinical data were obtained from antenatal and hospital records. Renal damage was evaluated by a (99m) Tc-dimercaptosuccinic acid scan. Pregnancy blood pressure (BP), complications and UTIs were compared between women with and without renal damage. RESULTS: All women completed the investigations, 48 with and 24 without renal damage. No woman, irrespective of presence or absence of renal damage, was diagnosed with hypertension before the first pregnancy. Pregnancy-related hypertension was diagnosed in 10 of 151 pregnancies, all in women with renal damage. Preeclampsia occurred in four women. Women with renal damage had significantly higher systolic BP measured at the last antenatal visit of their first pregnancy, compared with women without renal damage (p = 0.005). During subsequent pregnancies both systolic and diastolic BP were significantly higher in women with than without renal damage (p = 0.02 and p = 0.03, respectively). CONCLUSION: In this population-based follow-up study we found a large proportion of women with renal damage after UTI in childhood. Women with renal damage had significantly higher BP during pregnancy compared with women without renal damage. Pregnancy-related hypertension was recorded only in women with renal damage. However, pregnancy complications, including preeclampsia, were few.

Urinary tract infection pattern in adult women followed from childhood.

BACKGROUND: The aim of this study was to describe the pattern of urinary tract infection (UTI) and bladder function in women who had experienced recurrent UTI in childhood, with and without consequent renal damage, and followed for three to four decades. METHODS: A population-based cohort of women who had been followed from the first UTI in childhood and previously studied at a median age of 27 years was studied at a median age of 41 years. Renal damage was evaluated by (99m)Tc-dimercaptosuccinic acid scan. Clinical data were collected on the pattern of recurrent UTIs and bladder function. RESULTS: A total of 86 women were investigated, of whom 58 had suffered renal damage and 28 were without. Febrile UTI in adulthood had occurred in 22 patients, once in 15 women and twice or more in seven women. There was a change in the infection pattern over time, evident already in childhood, that was characterized by a decrease in UTI frequency and a shift from febrile to non-febrile infections. A significant association was found between renal damage and febrile UTI (p = 0.046), and between abnormal bladder function and recurrent non-febrile UTI (p = 0.002). There was no relationship between persisting vesicoureteral reflux (VUR) and proneness to either symptomatic UTI (p = 0.99) or febrile UTI in adulthood (p = 0.14). CONCLUSIONS: Among this study cohort there was a continuously decreasing rate of febrile UTI in adulthood. Persisting VUR was not related to UTI in adulthood. Abnormal bladder function was related to non-febrile UTI but not to febrile UTI.

Urinary tract infection in infants: the significance of low bacterial count.

BACKGROUND: In national guidelines for urinary tract infection (UTI) in children, different cut-off levels for defining bacteriuria are used. In this study, the relationship between bacterial count in infant UTI and inflammatory parameters, frequency of vesicoureteral reflux (VUR), kidney damage, and recurrent UTI was analyzed. METHODS: We conducted a population-based retrospective study of 430 infants age <1 year with symptomatic UTI diagnosed by suprapubic aspiration. Clinical and laboratory parameters, findings on voiding cystourethrography and (99m)technetium dimercapto-succinic acid scintigraphy, and frequency of recurrence were related to bacterial count at the index UTI. RESULTS: Eighty-three (19%) infants had bacterial counts <100,000 colony-forming units (CFU)/ml and 347 (81%) had ≥100,000 CFU/ml. There was similar frequency of VUR (19% in both groups), kidney damage (17 and 23%, p = 0.33) and recurrent UTI (6 and 12%, p = 0.17) in the low and high bacterial group. Non-E. coli species were more prevalent (19 versus 6%, p = 0.0006) and mean C-reactive protein was lower (50 vs. 79 mg/l, p <0.0001) in the low bacteria group. CONCLUSIONS: UTI with low bacterial count is common and of importance since it may be associated with VUR and renal damage. Non-E. coli species and low inflammatory response were more prevalent in UTI with low bacterial count.

Renal function in adult women with urinary tract infection in childhood.

BACKGROUND: The risk of deterioration of renal function in patients with urinary tract infection (UTI)-associated renal damage over several decades is incompletely known but of importance in regard to follow-up. METHODS: A population-based cohort of women followed from their first UTI in childhood was studied at median age of 27 years and now at 41 years. Renal damage was evaluated by (99m)Tc-dimercaptosuccinic acid scan and glomerular filtration rate (GFR) by (51)Cr-edetic acid clearance. Extent of individual kidney damage was graded as class 1 to 3. RESULTS: Eighty-six women completed the investigation, 58 with renal damage, and 28 without. Of those with damage, one had chronic kidney disease (CKD) stage 3, 14 stage 2, and 43 stage 1. Women with bilateral damage had lower GFR than those with no or unilateral damage (p < 0.0001). Women with class 3 damage had numerically but not significantly lower GFR than the others with damage (p = 0.07). Between the two studies there was significant decrease of GFR in the group with bilateral damage (p = 0.01). CONCLUSIONS: Women with UTI-associated renal damage had remarkably well preserved renal function, but those with bilateral or severe individual kidney damage may be considered for regular monitoring of GFR and blood pressure.

Twenty-four-hour ambulatory blood pressure in adult women with urinary tract infection in childhood.

OBJECTIVE: To study 24-h ambulatory blood pressure (BP) and development of hypertension over four decades in women with childhood urinary tract infection (UTI) associated with renal damage. METHODS: A population-based group of 111 women was followed from their first UTI in childhood. The cohort was investigated at a median age of 27 years using standardized office BP measurement and was reinvestigated 15 years later with 24-h ambulatory BP monitoring (ABPM) and Tc-dimercaptosuccinic acid scan for evaluation of renal damage. RESULTS: Eighty-six women with median age 41 years completed the reinvestigation. Hypertension occurred in 26 women, four of 28 (14%) without and 22 of 58 (38%) with renal damage (P = 0.04). The hypertension was diagnosed before entry in seven and in the study by ABPM in another 19 women. In 78 women, of which 50 had renal damage, the ABPMs were correlated to renal damage. There was significant difference between the groups without and with renal damage when mean 24-h systolic, mean daytime systolic and mean night-time SBP were compared (P = 0.03, P = 0.04, P = 0.01, respectively). The results remained significant when the group with damage was divided into subgroups with increasing extent of damage: class 1, 2 and 3 (P = 0.01, P = 0.02, P = 0.008, respectively). CONCLUSION: Women with UTI-associated renal damage but well preserved function had significantly higher 24-h ambulatory BP and more often hypertension than comparable women without damage. This shows that women with UTI-associated renal damage are at increased risk of hypertension and should be considered for regular BP screening, preferably with 24-h ABPM.

Urinary tract infection in small outpatient children: the influence of age and gender on resistance to oral antimicrobials.

UNLABELLED: Urinary tract infection (UTI) is a common bacterial disease in small children in which treatment with antimicrobials is used. The worldwide increase of bacterial resistance to these drugs is threatening the efficacy of such treatment and may increase the risk for long-term damage. The aim of this retrospective study was to analyse the development of resistance to oral antimicrobials over a 10-year period in an unselected outpatient population of small children with first-time UTI. The patient material included 494 boys and 512 girls below 2 years of age with community acquired symptomatic UTI. Escherichia coli bacteria were isolated in 96 % of girls and 89 % of boys (p < 0.0001). The overall resistance of E. coli was 14 % to trimethoprim and below 1 % to cefadroxil and nitrofurantoin. Over the 10-year period, the trimethoprim resistance of E. coli increased from 5 to 17 % but remained unchanged to cefadroxil and nitrofurantoin. E. coli resistance to trimethoprim was related to age: 11 % below and 19 % above 9 months (p < 0.01). The increase in resistance over time and with age was found only in girls. CONCLUSION: The increasing resistance of E. coli to trimethoprim makes this drug less suitable for empiric treatment of UTI. Young children with UTI seem predisposed to early development of resistance. Therefore, surveillance of resistance to antimicrobials with special regard to age and gender is recommended.

Multi-center randomized controlled trial of cognitive treatment, placebo, oxybutynin, bladder training, and pelvic floor training in children with functional urinary incontinence.

OBJECTIVE: Functional urinary incontinence causes considerable morbidity in 8.4% of school-age children, mainly girls. To compare oxybutynin, placebo, and bladder training in overactive bladder (OAB), and cognitive treatment and pelvic floor training in dysfunctional voiding (DV), a multi-center controlled trial was designed, the European Bladder Dysfunction Study. METHODS: Seventy girls and 27 boys with clinically diagnosed OAB and urge incontinence were randomly allocated to placebo, oxybutynin, or bladder training (branch I), and 89 girls and 16 boys with clinically diagnosed DV to either cognitive treatment or pelvic floor training (branch II). All children received standardized cognitive treatment, to which these interventions were added. The main outcome variable was daytime incontinence with/without urinary tract infections. Urodynamic studies were performed before and after treatment. RESULTS: In branch I, the 15% full response evolved to cure rates of 39% for placebo, 43% for oxybutynin, and 44% for bladder training. In branch II, the 25% full response evolved to cure rates of 52% for controls and 49% for pelvic floor training. Before treatment, detrusor overactivity (OAB) or pelvic floor overactivity (DV) did not correlate with the clinical diagnosis. After treatment these urodynamic patterns occurred de novo in at least 20%. CONCLUSION: The mismatch between urodynamic patterns and clinical symptoms explains why cognitive treatment was the key to success, not the added interventions. Unpredictable changes in urodynamic patterns over time, the response to cognitive treatment, and the gender-specific prevalence suggest social stress might be a cause for the symptoms, mediated by corticotropin-releasing factor signaling pathways.

Adults with myelomeningocele: an interview study about life situation and bladder and bowel management.

AIM: To assess life situation, and bladder and bowel management in individuals with myelomeningocele (MMC) after transferal to adult medical care. MATERIALS AND METHODS: All individuals (134) with myelomeningocele from western Sweden, born before 1981, and assessed on at least two occasions by a pediatric urologist, were invited to participate in a telephone interview according to a structured protocol. Sixty-nine individuals (32 males, 37 females) with a median age of 34 years (range 27-50) agreed to participate. RESULTS: Sixty-two individuals (90%) passed high school or had university education and 46 (67%) were employed. Fifty-three (77%) had their own apartment and 27 (39%) lived with a partner. Clean intermittent catheterization was used by 49 (71%), more commonly in females (p < 0.05). Pads were used by 60 (87%) individuals. Ten (14%) had urotherapy support. Of those operated on, 16 (53%) had a consultation with a urologist every 3 years; the corresponding number for the non-operated was 12 (31%). Eight individuals were treated with anticholinergic drugs. None had support for improvement of the fecal emptying regimen. CONCLUSIONS: Of the participants in the study, one third had no or rare contact with a urologist, few had urotherapy support and none had support for bowel regimen.

Parental experiences and preferences regarding the treatment of vesicoureteral reflux.

OBJECTIVE: Dilating vesicoureteral reflux (VUR) has been linked to febrile urinary tract infection (UTI) and renal scarring. It is unclear, however, whether children with reflux should be treated surgically or medically, or just kept under close surveillance with prompt treatment of UTIs. This lack of evidence makes parental preferences a crucial factor in the choice of therapy. The Swedish Reflux Trial was set up to compare the three treatment alternatives prospectively. This paper focuses on parental experience and satisfaction after completing the trial. MATERIAL AND METHODS: A group of 203 children aged 12-24 months with reflux grade III or IV were randomly assigned to antibiotic prophylaxis (n = 69), surveillance (n = 68) or endoscopic injection treatment (n = 66) and followed closely for 2 years. Afterwards, the families were interviewed by an investigator not involved in the care of the children about their experience of the study. RESULTS: Parental satisfaction with the treatment given was high, with 53% scoring 5 and 35% 4 on a five-grade scale, with no difference between the three groups (p = 0.5). Recurrence of febrile UTI or new kidney scarring did not influence parental satisfaction. Even though the satisfaction was high regardless of therapy, parents of children in the prophylaxis group more often than others would have chosen another treatment if given a choice. CONCLUSIONS: As far as parental satisfaction and preferences are concerned, antibiotic prophylaxis, surveillance and injection treatment are equivalent treatment strategies in children with VUR.

Ultrasonography and renography to visualize upper urinary tract in children with meningomyelocele - a prospective study.

OBJECTIVE: Ultrasonography (US) is commonly used to visualize the upper urinary tract in children and adolescents with meningomyelocele (MMC). The aim of this investigation was to prospectively evaluate US in those with spinal angulation or obesity and compare it to the corresponding results obtained by mercaptoacetyltriglycine renography. PATIENTS AND METHODS: Twenty-five children and adolescents with MMC and pronounced angulation of the spine or obesity, were prospectively investigated with both US and renography during the period 2006 to 2008. RESULTS: In 13 (52%) patients the kidneys could not be fully evaluated; in 4 (16%) neither renal size nor pelvic dilation, in 12 (48%) renal length and in 5 (20%) dilation was not accessible. In 23 individuals where dilatation could be evaluated uni- or bilaterally, US was compared to OEE% (%outflow excretion efficiency) at renography. In 1 of these individuals there was normal OEE% while slight dilatation on US was noticed. In 2/15 individuals, split function at renography did not correlate with renal length on US. CONCLUSION: Severe spinal angulation and obesity in individuals with MMC reduced the possibility to evaluate the urinary tract by US. However, it seems that renography could be a reliable alternative to evaluate renal condition in those patients where US is insufficient.

The Swedish reflux trial: review of a randomized, controlled trial in children with dilating vesicoureteral reflux.

OBJECTIVES: To evaluate prophylaxis and endoscopic injection for children with dilating vesicoureteral reflux (VUR) compared to surveillance, regarding urinary tract infection (UTI) recurrence, new renal damage, VUR outcome, and impact of lower urinary tract (LUT) dysfunction on these outcomes. PATIENTS AND METHODS: 203 children (128 girls and 75 boys), aged 1 to <2 years, with VUR grade III or IV were randomized to antibiotic prophylaxis (n = 69), endoscopic injection (n = 66) or surveillance (n = 68). Voiding cystourethrography, dimercaptosuccinic acid scintigraphy and optional LUT function assessment were performed before randomization and after 2 years. RESULTS: There were 67 febrile UTIs in 42 girls and 8 in 7 boys (p = 0.0001). In girls, recurrence rate was 19% on prophylaxis, 23% with endoscopic treatment and 57% on surveillance (p = 0.0002). In boys, there was no difference between treatment groups. New damage was seen in 13 girls: 8 on surveillance, 5 in the endoscopic group and none on prophylaxis (p = 0.0155), and in 2 boys. In 13 children with no or non-dilating VUR after 1 injection, dilating VUR reappeared at the 2-year follow up. LUT dysfunction at follow up was associated with persistence of VUR. CONCLUSION: In girls, prophylaxis reduced the rate of UTI recurrence and new renal damage, and endoscopic injection the rate of UTI recurrence. Boys did not benefit from active treatment.

Imaging strategy for infants with urinary tract infection: a new algorithm.

PURPOSE: We analyzed clinical data for prediction of permanent renal damage in infants with first time urinary tract infection. MATERIALS AND METHODS: This population based, prospective, 3-year study included 161 male and 129 female consecutive infants with first time urinary tract infection. Ultrasonography and dimercapto-succinic acid scintigraphy were performed as acute investigations and voiding cystourethrography within 2 months. Late scintigraphy was performed after 1 year in infants with abnormality on the first dimercapto-succinic acid scan or recurrent febrile urinary tract infections. End point was renal damage on the late scan. RESULTS: A total of 270 patients had end point data available, of whom 70 had renal damage and 200 did not. Final kidney status was associated with C-reactive protein, serum creatinine, temperature, leukocyturia, non-Escherichia coli bacteria, anteroposterior diameter on ultrasound and recurrent febrile urinary tract infections. In stepwise multiple regression analysis C-reactive protein, creatinine, leukocyturia, anteroposterior diameter and non-E.coli bacteria were independent predictors of permanent renal damage. C-reactive protein 70 mg/l or greater combined with anteroposterior diameter 10 mm or greater had sensitivity of 87% and specificity of 59% for renal damage. An algorithm for imaging of infants with first time urinary tract infection based on these results would have eliminated 126 acute dimercapto-succinic acid scans compared to our study protocol, while missing 9 patients with permanent renal damage. CONCLUSIONS: C-reactive protein can be used as a predictor of permanent renal damage in infants with urinary tract infection and together with anteroposterior diameter serves as a basis for an imaging algorithm.

Pathogen specific, IRF3-dependent signaling and innate resistance to human kidney infection.

The mucosal immune system identifies and fights invading pathogens, while allowing non-pathogenic organisms to persist. Mechanisms of pathogen/non-pathogen discrimination are poorly understood, as is the contribution of human genetic variation in disease susceptibility. We describe here a new, IRF3-dependent signaling pathway that is critical for distinguishing pathogens from normal flora at the mucosal barrier. Following uropathogenic E. coli infection, Irf3(-/-) mice showed a pathogen-specific increase in acute mortality, bacterial burden, abscess formation and renal damage compared to wild type mice. TLR4 signaling was initiated after ceramide release from glycosphingolipid receptors, through TRAM, CREB, Fos and Jun phosphorylation and p38 MAPK-dependent mechanisms, resulting in nuclear translocation of IRF3 and activation of IRF3/IFNß-dependent antibacterial effector mechanisms. This TLR4/IRF3 pathway of pathogen discrimination was activated by ceramide and by P-fimbriated E. coli, which use ceramide-anchored glycosphingolipid receptors. Relevance of this pathway for human disease was supported by polymorphic IRF3 promoter sequences, differing between children with severe, symptomatic kidney infection and children who were asymptomatic bacterial carriers. IRF3 promoter activity was reduced by the disease-associated genotype, consistent with the pathology in Irf3(-/-) mice. Host susceptibility to common infections like UTI may thus be strongly influenced by single gene modifications affecting the innate immune response.

Toll-like receptor 4 promoter polymorphisms: common TLR4 variants may protect against severe urinary tract infection.

BACKGROUND: Polymorphisms affecting Toll-like receptor (TLR) structure appear to be rare, as would be expected due to their essential coordinator role in innate immunity. Here, we assess variation in TLR4 expression, rather than structure, as a mechanism to diversify innate immune responses. METHODOLOGY/PRINCIPAL FINDINGS: We sequenced the TLR4 promoter (4,3 kb) in Swedish blood donors. Since TLR4 plays a vital role in susceptibility to urinary tract infection (UTI), promoter sequences were obtained from children with mild or severe disease. We performed a case-control study of pediatric patients with asymptomatic bacteriuria (ABU) or those prone to recurrent acute pyelonephritis (APN). Promoter activity of the single SNPs or multiple allelic changes corresponding to the genotype patterns (GPs) was tested. We then conducted a replication study in an independent cohort of adult patients with a history of childhood APN. Last, in vivo effects of the different GPs were examined after therapeutic intravesical inoculation of 19 patients with Escherichia coli 83972. We identified in total eight TLR4 promoter sequence variants in the Swedish control population, forming 19 haplotypes and 29 genotype patterns, some with effects on promoter activity. Compared to symptomatic patients and healthy controls, ABU patients had fewer genotype patterns, and their promoter sequence variants reduced TLR4 expression in response to infection. The ABU associated GPs also reduced innate immune responses in patients who were subjected to therapeutic urinary E. coli tract inoculation. CONCLUSIONS: The results suggest that genetic variation in the TLR4 promoter may be an essential, largely overlooked mechanism to influence TLR4 expression and UTI susceptibility.

The Swedish reflux trial in children: I. Study design and study population characteristics.

PURPOSE: We compared the rates of febrile urinary tract infection, kidney damage and reflux resolution in children with vesicoureteral reflux treated in 3 ways, including antibiotic prophylaxis, endoscopic therapy and surveillance with antibiotics only for symptomatic urinary tract infection. MATERIALS AND METHODS: Children 1 to younger than 2 years with grade III-IV reflux were recruited into this prospective, open, randomized, controlled, multicenter study and followed for 2 years after randomization. The main study end points were recurrent febrile urinary tract infection, renal status on dimercapto-succinic acid scintigraphy and reflux status. Outcomes were analyzed by the intent to treat principle. RESULTS: During a 6-year period 128 girls and 75 boys entered the study. In 96% of cases reflux was detected after urinary tract infection. The randomization procedure was successful and resulted in 3 groups matched for relevant factors. Recruitment was slower than anticipated but after patients were entered adherence to the protocol was good. Of the children 93% were followed for the intended 2 years without a treatment arm change. All except 2 patients completed 2-year followup scintigraphy. CONCLUSIONS: Recruitment was difficult but a substantial number of children were entered and randomly assigned to 3 groups with similar basic characteristics. Good adherence to the protocol made it possible to address the central study questions.

The Swedish reflux trial in children: II. Vesicoureteral reflux outcome.

PURPOSE: We compared reflux status in children with dilating vesicoureteral reflux treated in 3 groups, including low dose antibiotic prophylaxis, endoscopic therapy and a surveillance group on antibiotic treatment only for febrile urinary tract infection. MATERIALS AND METHODS: A total of 203 children 1 to younger than 2 years with grade III-IV reflux were recruited into this open, randomized, controlled trial. Endoscopic treatment was done with dextranomer/hyaluronic acid copolymer. The main end point was reflux status after 2 years. Data were analyzed by the intent to treat principle. RESULTS: Reflux status improved in all 3 treatment arms. Of patients in the prophylaxis, endoscopic and surveillance groups 39%, 71% and 47%, respectively, had reflux resolution or downgrading to grade I-II after 2 years. This was significantly more common in the endoscopic than in the prophylaxis and surveillance groups (p = 0.0002 and 0.0030, respectively). After 1 or 2 injections 86% of patients in the endoscopic group had no or grade I-II reflux but recurrent dilating reflux was seen in 20% after 2 years. CONCLUSIONS: Endoscopic treatment resulted in dilating reflux resolution or downgrading in most treated children. After 2 years endoscopic treatment results were significantly better than the spontaneous resolution rate or downgrading in the prophylaxis and surveillance groups. However, of concern is the common reappearance of dilating reflux after 2 years.

The Swedish reflux trial in children: v. Bladder dysfunction.

PURPOSE: We investigated the prevalence and types of lower urinary tract dysfunction in children with vesicoureteral reflux grades III and IV, and related improved dilating reflux, renal damage and recurrent urinary tract infection to dysfunction. MATERIALS AND METHODS: A total of 203 children between ages 1 to less than 2 years with reflux grades III and IV were recruited into this open, randomized, controlled, multicenter study. Voiding cystourethrography and dimercapto-succinic acid scintigraphy were done at study entry and 2-year followup. Lower urinary tract function was investigated by noninvasive methods, at study entry with 4-hour voiding observation in 148 patients and at 2 years by structured questionnaire and post-void residual flow measurement in 161. RESULTS: At study entry 20% of patients had lower urinary tract dysfunction, characterized by high bladder capacity and increased post-void residual urine. At 2 years there was dysfunction in 34% of patients. Subdivision into groups characteristic of children after toilet training revealed that 9% had isolated overactive bladder and 24% had voiding phase dysfunction. There was a negative correlation between dysfunction at 2 years and improved dilating reflux (p = 0.002). Renal damage at study entry and followup was associated with lower urinary tract dysfunction at 2 years (p = 0.001). Recurrent urinary tract infections were seen in 33% of children with and in 20% without dysfunction (p = 0.084). CONCLUSIONS: After toilet training a third of these children with dilating reflux had lower urinary tract dysfunction, mainly voiding phase problems. Dysfunction was associated with persistent reflux and renal damage while dysfunction at study entry did not predict the 2-year outcome.