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.

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.

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.

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.

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.

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.

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.

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.

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.

Value of ultrasound in evaluation of infants with first urinary tract infection.

PURPOSE: We evaluated the role of ultrasound in diagnosing and treating infants with a first urinary tract infection with a focus on important structural abnormalities. MATERIALS AND METHODS: In a setting of limited prenatal ultrasound screening this population based, prospective, 3-year study included 161 male and 129 female infants. Ultrasound and dimercapto-succinic acid scintigraphy were performed as initial investigations and voiding cystourethrography was conducted within 2 months. RESULTS: Ultrasound revealed dilatation in 15% of patients and increased kidney length in 28%. Sensitivity for detecting scintigraphic abnormality was 48%. Renal length was significantly correlated to inflammatory parameters, including scintigraphic abnormalities. Important structural abnormalities were detected in 40 cases, with 30 on ultrasound, while 10 of 27 cases of dilating reflux (mostly grade III) were missed. Outside the study there were 28 additional cases of structural abnormality, of which 15 were detected prenatally. CONCLUSIONS: Ultrasound detected most structural abnormalities except grade III reflux. Since it is noninvasive, ultrasound has a place in the evaluation of infants with urinary tract infection, especially in the absence of prenatal ultrasound during late pregnancy. Kidney length in infants with acute infection correlated with inflammatory parameters, and the clinical importance of this finding needs to be studied further.

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.

The Swedish reflux trial in children: III. Urinary tract infection pattern.

PURPOSE: We evaluated the difference in the febrile urinary tract infection rate in small children with dilating vesicoureteral reflux randomly allocated to 3 management alternatives, including antibiotic prophylaxis, endoscopic treatment or surveillance only as the control. MATERIALS AND METHODS: At 23 centers a total of 203 children were included in the study, including 128 girls and 75 boys 1 to younger than 2 years. Vesicoureteral reflux grade III in 126 cases and IV in 77 was detected after a febrile urinary tract infection (194) after prenatal screening (9). Voiding cystourethrography and dimercapto-succinic acid scintigraphy were done before randomization and after 2 years. The febrile urinary tract infection rate was analyzed by the intent to treat principle. RESULTS: We noted a total of 67 febrile recurrences in 42 girls and a total of 8 in 7 boys (p = 0.0001). There was a difference in the recurrence rate among treatment groups in girls with febrile infection in 8 of 43 (19%) on prophylaxis, 10 of 43 (23%) with endoscopic therapy and 24 of 42 (57%) on surveillance (p = 0.0002). In girls the recurrence rate was associated with persistent reflux after 2 years (p = 0.0095). However, reflux severity (grade III or IV) at study entry did not predict recurrence. CONCLUSIONS: In this randomized, controlled trial there was a high rate of recurrent febrile urinary tract infection in girls older than 1 year with dilating vesicoureteral reflux at study entry but not in boys. Antibiotic prophylaxis and endoscopic treatment decreased the infection rate.

The Swedish reflux trial in children: IV. Renal damage.

PURPOSE: We compared the development of new renal damage in small children with dilating vesicoureteral reflux randomly allocated to antibiotic prophylaxis, endoscopic treatment or surveillance as the control group. MATERIALS AND METHODS: Included in the study were 128 girls and 75 boys 1 to younger than 2 years with grade III-IV reflux. Voiding cystourethrography and dimercapto-succinic acid scintigraphy were done before randomization and after 2 years. Febrile urinary tract infections were recorded during followup. Data analysis was done by the intent to treat principle. RESULTS: New renal damage in a previously unscarred area was seen in 13 girls and 2 boys. Eight of the 13 girls were on surveillance, 5 received endoscopic therapy and none were on prophylaxis (p = 0.0155). New damage was more common in children with than without febrile recurrence (11 of 49 or 22% vs 4 of 152 or 3%, p <0.0001). CONCLUSIONS: In boys the rate of new renal damage was low. It was significantly higher in girls and most common in the control surveillance group. There was also a strong association between recurrent febrile UTIs and new renal damage in girls.

Predictive factors for resolution of congenital high grade vesicoureteral reflux in infants: results of univariate and multivariate analyses.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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, p <0.0001), bladder dysfunction (hazard ratio 0.43, 95% CI 0.29-0.64, p <0.0001) 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%. CONCLUSIONS: 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.

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.

Longitudinal development of renal damage and renal function in infants with high grade vesicoureteral reflux.

PURPOSE: We sought to study renal abnormality and renal function through time in infants with high grade vesicoureteral reflux. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Urinary proteins in children with urinary tract infection.

The aim of this study was to test our hypothesis that the urinary excretion of C-reactive protein (CRP), alpha 1-microglobulin (A1M), retinol-binding protein (RBP) and Clara cell protein (CC16) is increased in children with urinary tract infection (UTI) and relates to renal damage as measured by acute dimercaptosuccinic acid (DMSA) scintigraphy. Fifty-two children <2 years of age with UTI were enrolled in the study, 44 of whom were febrile. The control group consisted of 23 patients with non-UTI infection and elevated serum CRP (s-CRP) levels. Thirty-six patients had abnormal DMSA uptake, classified as mild, moderate or severe damage (DMSA class 1, 2, 3, respectively). There was a significant association between DMSA class and the excretion of urinary RBP (u-RBP) and u-CC16. There was also a significant difference in u-CRP levels between children with UTI and control children with non-UTI infections, although u-CRP excretion was not significantly correlated to DMSA class. In conclusion, the urinary excretion of the low-molecular-weight proteins RBP and CC16 showed a strong association with uptake defects on renal DMSA scans. The urinary level of CRP seems to distinguish between children with UTI and other febrile conditions. A combination of these biomarkers may be useful in the clinical assessment of children with UTI.