Early Performance of Imaging Studies After First Urinary Tract Infection
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Khaled M. Amro, M.D*, Mohamed Alnaji, M.D, Salem Al-Zawahri, M.D, Mustafa Al-Zboon, M.D, Mohamed I. Aladwan, M.D.
*Pediatrician from department of pediatric RMS, at Prince Hashim Hospital Zarqa-Jordan.

Correspondence:
Dr. Khaled Amro
P.O. Box 1196 Zarqa-Jordan
E-mail: drkhaledam64@yahoo.com

The main goals of imaging studies in children with a first episode of urinary tract infection (UTI) are to identify urinary tract anatomic abnormalities. If such abnormalities are found, therapeutic measures are executed in order to prevent future infections and possible long term damage to the kidneys.

Currently, the recommended imaging study is renal ultrasound (RUS), which mainly detects abnormalities in the upper urinary tract such as hydronephrosis or obstruction. Furthermore, radiologists often report various degrees of dilatation of the collecting system of the kidney and urinary tract on renal ultrasound, suggesting that further investigation for VUR should be done. The standard test used to diagnose VUR is voiding cysto- urethrogram. The generally accepted practice is to perform VCUG in all children younger than 5 years old with first documented UTI. For children older than 5, the recommendations vary according to gender, clinical manifestations and family history of VUR^1-3. The accepted practice has been to perform VCUG at least 3-6 weeks after a UTI in order to prevent false positive results, which may be caused by UTI-related transient changes in the urinary tract^4,5. However, the validity of this practice has recently been questioned. Two recent retrospective studies^6,7 and one cross-sectional analysis⁸ have shown that the prevalence and severity of VUR in children with UTI were not influenced by the timing of VCUG performance (i.e., early vs. late performance following the diagnosis of UTI). In a study investigating the optimal timing of voiding cystourethrogram (VCUG) after UTI, only 48% of patients had their scheduled VCUG performed.⁶ This may be related to the invasive nature of the VCUG, which requires urethral catheterisation. Furthermore, parents and physicians may be reassured by a normal ultrasound, and forgo performing the VCUG. The objective of this study was to determine whether the presence of a dilated collecting system of the kidney and urinary tract, as reported by radiologists, predicted the presence of VUR on VCUG.

The purpose of this study was to prospectively evaluate the prevalence and grade of VUR in children with first documented UTI in whom RUS was performed early (within 2 days) after the diagnosis of UTI, to evaluate whether early detection of mild to moderate renal pelvic dilatation suggest VUR and VCUG performance poses an increased risk for UTI, and to examine whether early performance of RUS and VCUG improves the likelihood of having this study performed.

We prospectively evaluated children of both genders under the age of 5 years who were hospitalized over a 14 month period (April 2006 to July 2007) with first documented UTI at Prince Hashim Hospital in Zarqa city. This central care hospital serves a population of approximately half a million children of various ethnic origins in eastern of capital (Amman- Jordan.

Urinary tract infection was diagnosed when a symptomatic child had a culture of a urine specimen obtained by suprapubic aspiration growing any number of colonies, a catheterized specimen growing > 104 colonies/ml, or a properly obtained, clean-voided, midstream urine specimen growing = 105 colonies/ml. Patients with a previous history of UTI, known VUR or other genitourinary anomalies were excluded from the study.

The original study design was to perform RUS within 2 days from the diagnosis of UTI in all patients who met the study's inclusion criteria, and in whom parental consent was obtained.

In fact, the study group was divided into two subgroups based on the timing of RUS: an "early group" (group A) in which RUS was performed within 2 days from the occurrence of UTI, and a "late group" (group B) in which RUS was performed later than 2 days from the diagnosis of UTI (due to delays caused by parents, primary care physicians, or the health management organization). RUS results of groups A and B were compared with the results of this procedure in a historical control group (group C), which included children with first documented UTI who were hospitalized at Prince Hashim hospital between June 2004 and May 2005 and in whom RUS was performed more than 2 weeks after the diagnosis of UTI. The data on this group were collected retrospectively (RUS results) and prospectively (clinical data).

n = number of children
* Not significant vs. groups B and C

Patients in study groups A and B who had voiding cystourethrography given oral antibiotic prophylacticaly one day before and three days after procedures to prevent VCUG-associated sequelae such as fever, chills or other evidence of UTI.

n = number of children
* Not significant vs. groups B and C

During the study, 84 children under the age of 5 years with first documented UTI who met the inclusion criteria of the study were admitted to Prince Hashim Hospital. RUS then VCUG was performed in 78 patients who were divided into two subgroups. Group A comprised patients in whom RUS was performed within 2 days from the diagnosis (mean 1.5 days, range 1-2 days).

Group B comprised patients in whom RUS was performed more than 2 days after the diagnosis of UTI (mean 6 days, range 2-10 days). In 6 of 84 patients (7.1%) who were supposed to be included in the original group B, RUS was not performed. In five cases, the parents refused to expose the child to other procedure VCUG and one patient was lost to follow-up. RUS and VCUG was performed in all 49 patients who belonged to original group A. In 6/35 patients (17.1%) who belonged to original group B the procedure was not performed.

Group C comprised a historical control group of children in whom RUS was performed > 2 weeks from the diagnosis [Table 1]. In 34 of 116 patients (29.3%) who were supposed to be included in the original group C, the procedure was not performed. No statistically significant differences in gender and age were observed between the three study groups [Table 1]. Tables 2, and 3summarize the rates and grades of VUR within the three study groups. No statistically significant differences were found between groups A and B in term of rate and severity of reflux. The findings in both study groups were compared to those in the historical control group (group C) in which RUS and VCUG was performed more than 2 weeks after the diagnosis of UTI. No statistically significant differences were found between this group and group A in terms of rate and severity of renal pelvic dilatation. The overall rate of VUR in all patients in group A, B and C combined was 38.5% (30/78).

Early performance of RUS followed by VCUG was safe. Mild sequelae included: a) occurrence of fever without evidence of UTI in two patients in group A (1 and 4 days following the procedure, respectively, and b) the development of UTI caused by Pseudomonas aeruginosa in one patient in group B following a VCUG performed 2 months after the initial UTI.

n = number of children
* Not significant vs. groups B and C

For a first episode UTI in infants, renal ultrasound is performed to rule out anatomic abnormalities of the urinary tract. It is a non-invasive form of imaging performed before the VCUG and after the initial infection. Various degrees of dilatation of the collecting system of the kidney seen on renal ultrasound are often reported. A Medline search, however, found only three studies that examined the significance of these findings in children. Davey and colleagues⁹ looked at older children (mean age 4.2 years) who were referred for renal ultrasound and VCUG for a variety of indications, including UTI. They found that the frequency of VUR in children with mild renal pelvic distension did not differ significantly from that in children with no distension on renal ultrasound (39% v 32%, p = 0.365). Blane and colleagues¹⁰ retrospectively analysed VCUG and ultrasound results of 493 children. All children who had a VCUG within eight hours of a renal ultrasound scan were included, except for children with myelomeningocoele or renal surgery. The mean age of their study population was 4.9 years. They found that ultrasound was not sensitive for VUR. Of the kidneys with VUR, 74% had normal ultrasound scans.

DiPietro and colleagues¹¹ found that ultrasound was unreliable in excluding VUR in children aged 5 years or older who were being evaluated for a UTI. Only two of 21 children with VUR on VCUG had abnormal renal ultrasound scans.

In our study we prospectively evaluated VCUG findings in children with first documented UTI in our institution. The original design of our study was to perform VCUG within 2 days from the diagnosis of UTI in all children studied and to compare these findings with those of a historical control study group. Nevertheless, in 29 of the 84 children enrolled in the study early VCUG was not performed for various reasons (see Results). Those children in whom VCUG was performed more than 2 days after the diagnosis of UTI constituted a prospective control group, which, together with the historical control group, served to underscore the meaningful findings of this study.

McDonald et al.⁶ showed in their retrospective study that in 50% of children in whom VCUG was not performed early, the procedure was not performed at all. In our prospective study, 17% of patients in the original group B (the "late group") and 29.3% of patients in the original group C (the historical control group) did not undergo the study. Based on these findings we conclude that postponing the performance of RUS followed by VCUG reduces the likelihood of performing the procedure.

The question whether VCUG should be performed during the initial hospitalization in a child with documented UTI, while receiving the initial antibiotic therapy and following an appropriate clinical response, remains open. The medical and financial implications of such a practice should be investigated.

McDonald and co-workers⁶ showed that there was no difference in the rate and grade of reflux between children in whom VCUG was performed early (within 7 days from the diagnosis of UTI) and children who had VCUG later. In another study, Mahant et al.⁷ showed that performing an early VCUG did not influence the rate of detected reflux. It should be noted, however, that both studies were conducted retrospectively.

Renal ultrasound findings are neither sensitive nor specific for VUR in children with a first UTI.We conclude that early performance of VCUG (within 2 days) after first documented UTI does not influence the rate or severity of the detected VUR, does not augment the risk of secondary infection, shortens the period during which prophylactic antibiotic therapy is given, and increases the rate performance of the procedure, thereby minimizing the risk of failure to detect VUR. The traditional recommendation of performing VCUG 3-6 weeks after the diagnosis of UTI should be reassessed.

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