Renal Scarring In Children Research Articles

Renal Scarring in the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) Trial.

The main objectives of the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial were to evaluate the role of antimicrobial prophylaxis in the prevention of recurrent urinary tract infection (UTI) and renal scarring in children with vesicoureteral reflux (VUR). We present a comprehensive evaluation of renal scarring outcomes in RIVUR trial participants. This multicenter, randomized, placebo-controlled trial enrolled 607 children aged 2-71 months with grade 1-4 VUR diagnosed after a first or second febrile or symptomatic UTI. Study participants received trimethoprim-sulfamethoxazole or placebo and were followed for 2 years. Renal scarring was evaluated by baseline and follow-up (99m)technetium dimercaptosuccinic acid (DMSA) renal scans that were reviewed independently by two blinded reference radiologists. At the end of the study, 58 (10%) of 599 children and 63 (5%) of 1197 renal units had renal scarring. New renal scarring did not differ between the prophylaxis and placebo groups (6% versus 7%, respectively). Children with renal scarring were significantly older (median age, 26 versus 11 months; P=0.01), had a second UTI before enrollment (odds ratio [OR], 2.85; 95% confidence interval [95% CI], 1.38 to 5.92), were more likely to be Hispanic (OR, 2.22; 95% CI, 1.13 to 4.34), and had higher grades of VUR (OR, 2.79; 95% CI, 1.56 to 5.0). The proportion of new scars in renal units with grade 4 VUR was significantly higher than in units with no VUR (OR, 24.2; 95% CI, 6.4 to 91.2). Significantly more renal scarring was seen in relatively older children and in those with a second episode of febrile or symptomatic UTI before randomization. Preexisting and new renal scars occurred significantly more in renal units with grade 4 VUR than in those with low-grade or no VUR. Antimicrobial prophylaxis did not decrease the risk of renal scarring.

Risk Factors for Recurrent Urinary Tract Infection and Renal Scarring.

To identify risk factors for recurrent urinary tract infection (UTI) and renal scarring in children who have had 1 or 2 febrile or symptomatic UTIs and received no antimicrobial prophylaxis. This 2-year, multisite prospective cohort study included 305 children aged 2 to 71 months with vesicoureteral reflux (VUR) receiving placebo in the RIVUR (Randomized Intervention for Vesicoureteral Reflux) study and 195 children with no VUR observed in the CUTIE (Careful Urinary Tract Infection Evaluation) study. Primary exposure was presence of VUR; secondary exposures included bladder and bowel dysfunction (BBD), age, and race. Outcomes were recurrent febrile or symptomatic urinary tract infection (F/SUTI) and renal scarring. Children with VUR had higher 2-year rates of recurrent F/SUTI (Kaplan-Meier estimate 25.4% compared with 17.3% for VUR and no VUR, respectively). Other factors associated with recurrent F/SUTI included presence of BBD at baseline (adjusted hazard ratio: 2.07 [95% confidence interval (CI): 1.09-3.93]) and presence of renal scarring on the baseline (99m)Tc-labeled dimercaptosuccinic acid scan (adjusted hazard ratio: 2.88 [95% CI: 1.22-6.80]). Children with BBD and any degree of VUR had the highest risk of recurrent F/SUTI (56%). At the end of the 2-year follow-up period, 8 (5.6%) children in the no VUR group and 24 (10.2%) in the VUR group had renal scars, but the difference was not statistically significant (adjusted odds ratio: 2.05 [95% CI: 0.86-4.87]). VUR and BBD are risk factors for recurrent UTI, especially when they appear in combination. Strategies for preventing recurrent UTI include antimicrobial prophylaxis and treatment of BBD.

Role of Renal Ultrasonography in Predicting Vesicoureteral Reflux and Renal Scarring in Children Hospitalized with a First Febrile Urinary Tract Infection

This study was designed to examine the capability of renal ultrasonography (US) for predicting vesicoureteral reflux (VUR) and renal scarring (RS), and to assess, using initial US, the significant urologic abnormalities that impact on management of children hospitalized with a first febrile urinary tract infection (UTI). Hospitalized children aged ≤ 2 years with a first febrile UTI were prospectively evaluated using imaging studies, including (99m)Tc dimercaptosuccinic acid (DMSA) scan, US, and voiding cystourethrography. Of the 310 children analyzed (195 boys and 115 girls), 105 (33.9%) had abnormal US. Acute DMSA scans were abnormal in 194 children (62.6%), including 89 (45.9%) with concomitant abnormal US. There was VUR in 107 children (34.5%), including 79 (25.5%) with Grades III-V VUR. The sensitivity and negative predictive values of US were 52.3% and 75.1%, respectively, for Grades I-V VUR and 68.4% and 87.8%, respectively, for Grades III-V VUR. Eighty-five children (27.4%) had RS, including 55 (64.7%) with abnormal US. Of the 105 children with abnormal US, 33 (31.4%) needed subsequent management (surgical intervention, parental counseling, or follow up of renal function). Nephromegaly on initial US and Grades III-V VUR were risk factors of RS. Abnormal US may carry a higher probability of Grades III-V VUR and RS, and can affect subsequent management in a significant number of children. Nephromegaly on initial US and Grades III-V VUR are strongly associated with an increased risk for RS. Thus, US should be performed on children after a first febrile UTI and children with normal US may not require voiding cystourethrography.

Urinary Biomarkers for Screening for Renal Scarring in Children with Febrile Urinary Tract Infection: Pilot Study

Recurrent febrile urinary tract infections during infancy cause renal scarring, which is characterized by progressive focal interstitial fibrosis and may lead to renal failure. Renal scarring can be diagnosed through scintigraphy, although it seems impractical to perform renal scintigraphy for all infants with febrile urinary tract infections. Therefore, it is important to search for a biomarker to identify the presence of renal scarring. We hypothesized that urinary biomarkers of nephropathy may increase in infants with renal scarring following febrile urinary tract infections. A total of 49 infants who underwent renal scintigraphy for febrile urinary tract infections were enrolled in the study. Several measurements were performed using urine samples, including total proteins, beta2-microglobulins, N-acetyl-β-D-glucosaminidase, neutrophil gelatinase associated lipocalin, liver-type fatty acid binding protein and angiotensinogen. Values were corrected by creatinine and compared between patients with and without renal scarring. Among urinary biomarkers only angiotensinogen in patients with scarring (median 14.6 μg/gm creatinine) demonstrated significantly higher levels than in patients without scarring (3.6 μg/gm creatinine, p <0.001). Urinary angiotensinogen may be useful for diagnosing the presence of renal scarring.

Urodynamic disorders and renal scarring in pediatric patients with nonmonosymptomatic nocturnal enuresis.

In nonmonosymptomatic nocturnal enuresis (NMNE), the incidence of organic abnormality and urodynamic disorder is more frequent than the general population. The aim of this study is to identify urodynamic disorders and renal scarring in children with NMNE. This study evaluated the urodynamic disorders and renal scarring of a total of 30 patients who were diagnosed with NMNE. A video-urodynamic test and Tc-99m dimercaptosuccinic acid renal scintigraphy were applied. Records of 605 patients who had been diagnosed with enuresis were analyzed, and 215 (33.5%) of them had been diagnosed with NMNE. Thirty patients older than 6 years old with NMNE were included in the study. Detrusor overactivity was identified in 10 patients. Bladder capacity was low in 5 patients and bladder compliance was low in 2 patients. Renal scarring was identified in 1 patient. Unilateral vesicoureteral reflux was found in 4 patients. Bladder function disorder is also a significant risk factor for the development of renal scarring, besides other risk factors. Organic abnormalities are seen more often in patients with NMNE than patients with monosymptomatic nocturnal enuresis, so urodynamic studies should be remembered for patients with NMNE.

Identification of children and adolescents at risk for renal scarring after a first urinary tract infection: a meta-analysis with individual patient data.

No studies have systematically examined the accuracy of clinical, laboratory, and imaging variables in detecting renal scarring in children and adolescents with a first urinary tract infection. To identify independent prognostic factors for the development of renal scarring and to combine these factors in prediction models that could be useful in clinical practice. MEDLINE and EMBASE. We included patients aged 0 to 18 years with a first urinary tract infection who underwent follow-up renal scanning with technetium Tc 99m succimer at least 5 months later. We pooled individual patient data from 9 cohort studies. We examined the association between predictor variables assessed at the time of the first urinary tract infection and the development of renal scarring. Renal scarring was defined by the presence of photopenia on the renal scan. We assessed the following 3 models: clinical (demographic information, fever, and etiologic organism) and ultrasonographic findings (model 1); model 1 plus serum levels of inflammatory markers (model 2); and model 2 plus voiding cystourethrogram findings (model 3). Of the 1280 included participants, 199 (15.5%) had renal scarring. A temperature of at least 39°C, an etiologic organism other than Escherichia coli, an abnormal ultrasonographic finding, polymorphonuclear cell count of greater than 60%, C-reactive protein level of greater than 40 mg/L, and presence of vesicoureteral reflux were all associated with the development of renal scars (P ≤ .01 for all). Although the presence of grade IV or V vesicoureteral reflux was the strongest predictor of renal scarring, this degree of reflux was present in only 4.1% of patients. The overall predictive ability of model 1 with 3 variables (temperature, ultrasonographic findings, and etiologic organism) was only 3% to 5% less than the predictive ability of models requiring a blood draw and/or a voiding cystourethrogram. Patients with a model 1 score of 2 or more (21.7% of the sample) represent a particularly high-risk group in whom the risk for renal scarring was 30.7%. At this cutoff, model 1 identified 44.9% of patients with eventual renal scarring. Children and adolescents with an abnormal renal ultrasonographic finding or with a combination of high fever (≥39°C) and an etiologic organism other than E coli are at high risk for the development of renal scarring.

Efficacy of magnetic resonance urography in detecting renal scars in children with vesicoureteral reflux

The detection of renal scars is of paramount importance for optimal clinical management of patients with urinary tract infection (UTI) and vesicoureteral reflux (VUR). The aim of our study was to compare the efficacy of unenhanced magnetic resonance urography (MRU) and Tc-99(m) dimercaptosuccinic acid (Tc-DMSA) scintigraphy to dectect renal scars. Unenhanced MRU and Tc-DMSA scintigraphy were performed in 49 children (10 boys, 39 girls; mean age 7.4 ± 4.2 years, range 1-15 years) with documented VUR. MR imaging scans were obtained within 7 days after voiding cystourethrogram (VCUG) and Tc-DMSA scintigraphy. The diagnostic performance of MRU in renal scar detection was calculated relative to that of the Tc-DMSA scan. The renal scar detection rate of Tc-DMSA scintigraphy and unenhanced MRU in kidneys with VUR was 32.4 and 25.9%, respectively. The sensitivity and specificity of MRU in the detection of renal scars was 80 and 82.6% in kidneys with VUR, respectively. There was no statistically significant difference in lesion detection between MRU and Tc-DMSA scintigraphy (P > 0.05). MRU and Tc-DMSA scintigraphy showed good agreement (κ = 0.60). Unenhanced MRU is a robust technique for the morphologic assessment of the urinary system and detection of renal scars. The lack of radiation and contrast material makes this technique a much safer alternative to scintigraphy in children with VUR, particularly in those who require follow-up scanning and, consequently, considerable radiation exposure.

Prevalence and risk factors for renal scars in children with febrile UTI and/or VUR: A cross-sectional observational study of 565 consecutive patients

PurposeTo determine prevalence and risk factors for renal scar in children referred for urologic assessment of febrile UTI and/or VUR. MethodsPre-determined risk factors for renal scar were prospectively recorded in consecutive patients referred for UTI/VUR. Age, gender, VUR grade, and reported number of febrile and non-febrile UTIs were analyzed with logistic regression to determine risk for focal cortical defects on non-acute DMSA. ResultsOf 565 consecutive children, 24 (4%) had congenital renal dysplasia and 84 (15.5%) had focal defect(s). VUR, especially grades IV–V, recurrent febrile UTI, and older age increased risk. For any age child with the same number of UTIs, VUR increased odds of renal defect 5.4-fold (OR = 5.4, 95% CI = 2.7–10.6, AUC = 0.759). ConclusionsFocal DMSA defects were present in 15.5% of 565 consecutive children referred for febrile UTI and/or VUR; 4% had presumed congenital reflux nephropathy without cortical defect. All VUR grades increased risk for these defects, as did recurrent febrile UTIs and older age. However, 43% with grades IV–V VUR and 76% with recurrent UTI had normal DMSA.

Commentary to ‘Prevalence and risk factors for renal scars in children with febrile UTI and/or VUR: A cross-sectional observational study of 565 consecutive patients’

Commentary to ‘Prevalence and risk factors for renal scars in children with febrile UTI and/or VUR: A cross-sectional observational study of 565 consecutive patients’

Incidence of Abnormal Imaging and Recurrent Pyelonephritis after First Febrile Urinary Tract Infection in Children 2 to 24 Months Old

The AAP (American Academy of Pediatrics) no longer recommends voiding cystourethrogram in children 2 to 24 months old who present with a first urinary tract infection if renal-bladder ultrasound is normal. We identified factors associated with abnormal imaging and recurrent pyelonephritis in this population. We retrospectively evaluated children diagnosed with a first episode of pyelonephritis at age 2 to 24 months using de-identified electronic medical record data from an institutional database. Data included age at first urinary tract infection, gender, race/ethnicity, need for hospitalization, intravenous antibiotic use, history of abnormal prenatal ultrasound, renal-bladder ultrasound and voiding cystourethrogram results, urinary tract infection recurrence and surgical intervention. Risk factors for abnormal imaging and urinary tract infection recurrence were analyzed by univariate logistic regression, the chi-square test and survival analysis. We identified 174 patients. Of the 154 renal-bladder ultrasounds performed 59 (38%) were abnormal. Abnormal prenatal ultrasound (p = 0.01) and the need for hospitalization (p = 0.02) predicted abnormal renal-bladder ultrasound. Of the 95 patients with normal renal-bladder ultrasound 84 underwent voiding cystourethrogram. Vesicoureteral reflux was more likely in patients who were white (p = 0.003), female (p = 0.02) and older (p = 0.04). Despite normal renal-bladder ultrasound, 23 of 84 patients (24%) had dilating vesicoureteral reflux. Of the 95 patients with normal renal-bladder ultrasound 14 (15%) had recurrent pyelonephritis and 7 (7%) went on to surgical intervention. Despite normal renal-bladder ultrasound after a first pyelonephritis episode, a child may still have vesicoureteral reflux, recurrent pyelonephritis and the need for surgical intervention. If voiding cystourethrogram is deferred, parents should be counseled on these risks.

Risk factors for renal scarring in children with primary vesicoureteral reflux disease

To determine the incidence of renal scarring among patients with primary vesicoureteral reflux (VUR) and the possible risk factor(s), we studied 90 children (60 girls and 30 boys) with VUR followed in the Pediatric Nephrology Unit at the Ege University Hospital from 1998 to 2003. All the patients were assessed for VUR grade by voiding cystoureterography and for presence of renal scarring by (99 m) technetium dimercapto-succinic acid scintigraphy. All infants with VUR were given low-dose prophylactic antibiotics and followed-up until resolution of the reflux. Grade of reflux and number of urinary tract infection (UTI) episodes (≥3) were found to be statistically significant risk factors for renal scarring (P <0.05). However, gender, familial history and laterality of the disease were not found to be statistically significant risk factors (P >0.05). Similarly, there was no statistically significant difference of frequency of renal scarring among the different age groups (P >0.05). We conclude that recurrences of UTI and VUR severity are significant risk factors for renal scarring in children with VUR. Therefore, identification of VUR at an early age may offer the opportunity to prevent episodes of UTI and possible formation of renal scars that may result in end-stage renal failure.

Risk factors for renal scarring in children with primary vesicoureteral reflux disease

Risk factors for renal scarring in children with primary vesicoureteral reflux disease

Is Urinary Kidney Injury Molecule-1 a Noninvasive Marker for Renal Scarring in Children With Vesicoureteral Reflux?

To examine whether (1) levels of urinary kidney injury molecule-1 (KIM-1), a transmembrane protein and biomarker for renal tubular damage, increase in children with of vesicoureteral reflux (VUR), and (2) if KIM-1 predicts the grade of renal scarring in children with VUR. The study included 59 VUR patients with renal scarring, 5 VUR patients without renal scarring and 25 healthy controls aged 1 to 17 years. Dimercaptosuccinic acid scans were performed for determination of scarring and graded by 3 independent, blinded pediatric urologists for renal scarring according to the Randomized Intervention for Children with VUR study criteria. Spot urine samples were obtained. Urinary KIM-1 and creatinine levels were measured and the KIM-1/creatinine ratio was calculated. Urine geometric mean KIM-1 levels (ng/mg creatinine) were significantly higher in VUR patients than in healthy controls (P=.018). Although the correlation between VUR grade and geometric mean KIM-1 levels was not significant, a positive correlation was found for scarring grade and geometric mean KIM-1 levels (r=.30, P=.02). When the patients were divided by subgroups according to scarring grade (group I, grade 1; group II, grades 2 and 3; group III, grade 4), the log KIM-1 in group III was significantly higher than in group I (P=.004). Urinary KIM-1 levels might be used as a noninvasive marker, particularly in showing severe scarring in children with VUR.

The effect of vitamin E or vitamin A on the prevention of renal scarring in children with acute pyelonephritis

Numerous factors may contribute to renal tissue injury after urinary tract infection. We have evaluated the effects of vitamins A or E supplementation in combination with antibiotics for the prevention of renal scarring in acute pyelonephritis. A simple non-blind randomized clinical trial was conducted on 61 children aged 1 month to 10 years between 2004 and 2006. The inclusion criteria were positive urine culture, clinical findings, and 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy-based evidence in favor of acute pyelonephritis. The children were randomized into three treatment groups: 10-day treatment with only antibiotics (control group; n = 25) and 10-day treatment with supplements of vitamin A (n = 17) or vitamin E (n = 18) in addition to antibiotics during the acute phase of infection. The final analysis was performed after excluding male patients. Each patient was evaluated twice by 99mTc-DMSA scintigraphy performed at least 6 months apart. P < 0.05 was considered to be statistically significant. The analysis included 108 kidney units. The frequency of inflammation at the beginning of therapy was not significantly different in the three groups (63.3 % in vitamin A, 61 % in vitamin E, and 76.2 % in the control group). A worsening of lesions, based on the second 99mTc-DMSA scan, was observed in 42.5, 0, and 23.3 % of the control, vitamin E, and vitamin A patients, respectively (LR = 26.3, P < 0.001). Vitamins A or E supplements were effective in reducing renal scarring secondary to acute pyelonephritis.

Randomized trial of oral versus sequential intravenous/oral antibiotic for acute pyelonephritis in children

ObjectiveTo confirm whether oral antibiotic treatment is as efficacious as sequential intravenous/oral antibiotic treatment in the prevention of renal scarring in children with acute pyelonephritis and scintigraphy-documented acute lesions.MethodsIn a prospective multicenter trial of non inferiority, children aged 1 to 36 months with their first case of acute pyelonephritis, a serum procalcitonin concentration ≥ 0.5 ng/mL, no known uropathy, and a normal ultrasound exam were randomized into two treatment groups. They received either oral cefixime for 10 days or intravenous ceftriaxone for 4 days followed by oral cefixime for 6 days. Patients with acute renal lesions detected on early dimercaptosuccinic acid scintigraphy underwent a follow-up scintigraphy 6 to 8 months later.ResultsThe study included 171 infants and children. There were no significant differences between the two groups in any clinical characteristic. Initial scintigraphy results were abnormal for 119 children. Ninety-six children were measured for renal scarring at the follow-up scintigraphy (per protocol analysis population). The incidence of renal scarring was 30.8% in the oral treatment group and 27.3% for children who received the sequential treatment.ConclusionsAlthough this trial does not statistically demonstrate the non-inferiority of oral treatment compared with the sequential treatment, our study confirmed the results of previously published reports and therefore supports the use of an oral antibiotic treatment of primary episodes of acute pyelonephritis in infants and young children.

Identifying Children with Vesicoureteral Reflux: A Comparison of 2 Approaches

Various screening approaches have been proposed to identify the subgroup of children with urinary tract infection who have vesicoureteral reflux. However, few studies have compared the sensitivity of screening approaches in a representative population of young children. We compared the sensitivities of the top-down ((99m)technetium dimercaptosuccinic acid renal scan to screen) and biomarker based (C-reactive protein level at presentation) approaches in identifying children with vesicoureteral reflux. We calculated the sensitivity of the 2 screening approaches in detecting vesicoureteral reflux and subsequently high grade (III or greater) vesicoureteral reflux in children. The top-down and C-reactive protein based approaches missed 33% and 29% of cases of high grade vesicoureteral reflux, respectively. The sensitivity of the top-down approach for detecting high grade vesicoureteral reflux was lower than previously reported. Further study of novel methods to identify children at risk for renal scarring is warranted.

Urine endothelin-1 levels as a predictor of renal scarring in children with urinary tract infections

Endothelin-1 (ET-1) contributes to renal fibrogenesis in several manners such as increasing collagen synthesis in mesangium, decreasing extracellular matrix (ECM) degradation by mesangial cells and stimulating mesangial contraction. The aim of our study was to investigate whether urine level of ET-1 (uET-1) could represent a useful biomarker of renal scarring and if so, to determine the optimal cutoff level for uET-1 to predict a renal scar. 44 children with renal scarring and 32 children without renal scarring were enrolled in the study. Urine ET-1 was measured by enzyme-linked immunosorbent assay. Mean uET-1 level was significantly higher in the scar group than in controls (2.75 ± 1.35 fmol/ml vs. 0.68 ± 0.41 fmol/ml, p = 0.001). The optimal cut-off level was 1.064 fmol/ml for uET-1 to predict renal scarring. Using this cut-off point, sensitivity and specificity were 97.73% and 93.91%, respectively. AUC was found 0.975 (95% CI 0.917 - 0.996) for uET-1. Mean urine Endothelin-1/Creatinine ratio (uET-1/Cr) was also significantly higher in the scar group than in the control group (4.04 ± 2.29 fmol/mg Cr vs. 1.09 ± 0.67 fmol/mg Cr, p = 0.0001). Using 1.67 fmol/mgCr as optimal cut-off level, sensitivity and specificity were 95.45% and 84.09%, respectively. AUC was 0.945 (95% CI 0.875 - 0.982) for uET-1/Cr. Our study suggests that both uET-1 and uET-1/Cr can be used for prediction of renal scarring in children with normal renal function. Measuring urine level of ET-1 can help us to avoid unnecessary DMSA studies if the patient's uET-1 level is found to be under the determined cut-off point.

Risk factors of renal scars in children with acute pyelonephritis

OBJECTIVE: The aim of this study was to determine the association between previously documented risk factors such as recurrent pyelonephritis with the incidence of renal scarring after acute pyelonephritis in children. MATERIAL AND METHODS: Children with acute pyelonephritis who were admitted to the Department of Pediatrics of a teaching hospital during 2007-2009 were enrolled in this study. DMSA scans were obtained 4-6 months after the last episode of pyelonephritis in all patients. RESULTS: A total of 80 children with acute pyelonephritis were enrolled in this study. Most of them were girls (77.5%), with a median age of 12 months. Nearly half of the children (n = 44; 55%) had one or more renal scars. The distribution of gender, CRP level and leukocytosis did not differ significantly regardingthe absence or presence of renal scars (p > 0.05). Most of the scars occurred in children who had presented with bilateral pyelonephritis (69.4% vs. 18.2%, p = 0.001). Most of the patients with renal scars had a positive history of vesicoureteral reflux (VUR) (75% vs.13.6%, p = 0.001). The significant roles of recurrent pyelonephritis and presence of VUR were further confirmed by multivariate analysis. CONCLUSIONS: According to our findings, presence of VUR and recurrent pyelonephritis are independently associated with a higher incidence of renal scarring.

Randomized Trial of Oral Versus Sequential IV/Oral Antibiotic for Acute Pyelonephritis in Children

To confirm whether oral antibiotic treatment is as efficacious as sequential intravenous/oral antibiotic treatment in the prevention of renal scarring in children with acute pyelonephritis and scintigraphy-documented acute lesions. In a prospective multicenter trial, children aged 1 to 36 months with their first case of acute pyelonephritis, a serum procalcitonin concentration ≥0.5 ng/mL, no known uropathy, and a normal ultrasound exam were randomized into 2 treatment groups. They received either oral cefixime for 10 days or intravenous ceftriaxone for 4 days followed by oral cefixime for 6 days. Patients with acute renal lesions detected on early dimercaptosuccinic acid scintigraphy underwent a follow-up scintigraphy 6 to 8 months later. The study included 171 infants and children. There were no significant differences between the 2 groups in any clinical characteristic. Initial scintigraphy results were abnormal for 119 children. Ninety-six children were measured for renal scarring at the follow-up scintigraphy (per protocol analysis population). The incidence of renal scarring was 30.8% in the oral treatment group and 27.3% for children who received the sequential treatment. Although this trial does not statistically demonstrate the noninferiority of oral treatment compared with the sequential treatment, our study confirmed the results of previously published reports and therefore supports the use of an oral antibiotic treatment of primary episodes of acute pyelonephritis in infants and young children.

Risk Factors for Renal Scar Formation in Infants With First Episode of Acute Pyelonephritis: A Prospective Clinical Study

We prospectively determined the risk factors for renal scar formation after the first episode of acute pyelonephritis as confirmed on dimercapto-succinic acid scintigraphy in children younger than 1 year. A total of 213 infants with acute pyelonephritis were enrolled in the study. Infants with urological abnormalities other than vesicoureteral reflux were excluded from analysis. Followup scanning was performed 6 months after acute pyelonephritis and voiding cystourethrography was performed after the acute phase of infection. Possible risk factors were evaluated including gender, peak fever, duration of fever before and after treatment with antibiotics, white blood cell count, C-reactive protein concentration, presence of vesicoureteral reflux and reflux grade. Six months after acute pyelonephritis 37 of 213 (17.4%) infants and 41 of 248 (16.5%) renal units with acute photon defects on initial dimercapto-succinic acid scintigraphy had renal scars. The rates of scar formation were significantly higher in infants with vesicoureteral reflux than in those without (39.4% vs 7.5%, p <0.001, OR 9.433) and in renal units with vesicoureteral reflux than in those without (39.4% vs 8.2%, p <0.001, OR 7.237). Renal scar formation was related to reflux grade (none-8.2%, grade I-20%, grade II-22.7%, grade III-40%, grade IV-70%, grade V-55.6%, p <0.001) but not to any other clinical or laboratory variables. The presence of vesicoureteral reflux was the only independent risk factor for renal scar formation after acute pyelonephritis in infants. The prevalence of renal scarring was significantly correlated with reflux grade. Voiding cystourethrography is necessary in infants after the first acute pyelonephritis episode is confirmed on dimercapto-succinic acid renal scintigraphy.