Eira Stokland

THE NATURAL HISTORY OF BACTERIURIA IN CHILDHOOD

The highest figure for first-time UTI is found in infants below one year of age. These early infections are often pyelonephritic in character, but they are easily overlooked because symptoms are unspecific, high fever and failure to thrive being the most important. It has been shown that delay in start of treatment increases the risk of the child developing pyelonephritic scarring. There is reason to believe that undetected and therefore untreated attacks of pyelonephritis may be associated with renal scarring revealed later in life. This type of renal damage is associated with development of hypertension in about 10 per cent of children and it accounts for around 20 per cent of the children entered into dialysis and transplant programs. Prevention of such long-term problems would be of great value and pyelonephritic scarring is a potentially preventable disease. The majority of infants and young children with UTI are probably managed at the primary care level. It is therefore essential that general practitioners are well informed about the epidemiology of UTI in infancy and childhood and that adequate diagnostic facilities are provided. For example, suprapubic aspiration to obtain uncontaminated urine is a technique that may well be used in an outpatient setting, and dipslide cultures are accurate and inexpensive. In addition to young age, vesicoureteric reflux and repeated attacks of pyelonephritis are risk factors associated with development of renal scarring. Therefore, diagnostic imaging to detect children with anomalies within the urinary tract are especially important in the very young. Furthermore, long-term supervision should be provided and the parents advised to consult the doctor when there is suspicion of a new infection to avoid delay in treatment. There is no reason to perform general screening for bacteriuria in healthy infants. Although bacteriuria may be found in 1 to 2 per cent, asymptomatic children have a very high rate of spontaneous clearing of the bacteriuria and they seem to constitute a low-risk group. Instead, frequent culturing of urine from febrile infants would be much more important.

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.

Primary and acquired renal scarring in boys and girls with urinary tract infection

OBJECTIVES To determine when pyelonephritic renal scarring was detected in children with urinary tract infection (UTI) and characterize those with primary and acquired scarring, respectively. STUDY DESIGN A population-based cohort of 1221 children (989 girls and 232 boys) with first recognized symptomatic UTI, aged 0 to 15 years, were diagnosed and followed up prospectively at a single childrens hospital; 652 had febrile UTI. Seven hundred fifty-three were evaluated by urography. Renal scarring was classified as primary or acquired, the latter without signs of scarring at the first investigation. To evaluate the frequency of recurrent UTI in those with acquired scarring, a comparison with group-matched children without scarring was performed. RESULTS A total of 74 children without obstruction had renal scarring (acquired in 40). Primary scarring was found in 18 of 21 (86%) of the boys and 16 of 53 (30%) of the girls (P <.001). The majority of boys with scarring had dilated reflux (67%) in contrast to girls (23%). Recurrent UTI was rare in boys, whereas girls with acquired scarring had significantly more febrile recurrences than girls without scarring. CONCLUSIONS Most boys had primary, probably congenital, reflux-associated renal damage, whereas most girls had acquired scarring related to recurrences of febrile UTI.

Early 99mTc dimercaptosuccinic acid (DMSA) scintigraphy in symptomatic first-time urinary tract infection

During a 2 year period, 175 children below 6 years of age (median 0.4 year) with non‐obstructive symptomatic urinary tract infection were studied by 99mTc dimercaptosuccinic acid (DMSA) scintigraphy. DMSA scintigraphy was performed at a median of 10 days after the start of treatment and was abnormal in 73 children (42%), equivocal in 29 (16%) and normal in 73 (42%). Reflux was seen in 27% of all children and in 38% of the renal units that were abnormal at DMSA scintigraphy. A decreasing frequency of abnormalities at DMSA scintigraphy was seen within the first 14 days after the start of treatment. C‐reactive protein and grade of reflux correlated significantly with abnormal DMSA studies. To demonstrate renal involvement in acute urinary tract infection, DMSA scintigraphy should be performed within days after the start of treatment. It is noteworthy that reflux was seen in less than half of renal units with abnormal DMSA scintigraphy.

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.

Imaging of renal scarring

Children with urinary tract infection should be investigated and followed up, as those with pyelonephritis may develop renal scarring. In this review, after discussing the advantages and disadvantages of various imaging modalities for diagnosis of renal scarring, it is concluded that DMSA scintigraphy and urography can both be used to detect significant renal scarring. With DMSA scintigraphy, small renal lesions (functional uptake defects) not seen at urography will also be detected. The long‐term clinical significance of these lesions is, as yet, unknown. A normal DMSA scintigraphy after infection indicates low risk for clinically significant damage. In order to allow acute, reversible lesions to first disappear, a follow‐up DMSA examination should not be performed until at least 6 mo after the acute infection. Ultrasonography in isolation cannot be recommended for the diagnosis of renal scarring.

Reliability of ultrasonography in identification of reflux nephropathy in children

Objective: To assess the ability of ultrasonography to identify reflux nephropathy in children after urinary tract infection. Design: Ten experienced radiologists performed a total of 240 ultrasonographic examinations of kidneys in a one day study. The examiners were20unaware of the results of previous radiological and clinical examinations and of the proportions of normal and abnormal kidneys. Urography was used as method of reference, supported by static renal scintigraphy (dimercaptosuccinic acid labelled with technetium-99m) in half of the cases. Setting: Outpatient radiology department. Subjects: 25 children aged 2-16 years (20 kidneys with and 30 kidneys without renal scarring). Main outcome measures: Renal scarring. Overall size and length of kidneys. Sensitivity and specificity including receiver operator characteristics and variation between observers. Results - With renal scarring as the diagnostic20criterion and including cases classified as abnormal, probably abnormal, and uncertain the sensitivity of ultrasonography was 54% (specificity 80%). Addition of reduced renal size as a diagnostic criterion increased the sensitivity to 64% (specificity 79%). There were, however, wide variations between observers, with sensitivity ranging between 40% and 90% (specificity 94% to 65%). Conclusions: Because of its low sensitivity and specificity and poor agreement between observers, ultrasonography cannot be generally recommended for the detection of reflux nephropathy after urinary tract infection in children.

Evaluation of DMSA scintigraphy and urography in assessing both acute and permanent renal damage in children

Purpose: To evaluate dimercaptosuccinic acid (DMSA) scintigraphy and urography in the detection of renal involvement in children with urinary tract infection (UTI) in order to identify patients with a high risk of developing renal damage. Material and Methods: A total of 157 children (median age 0.4 years, range 5 days to 5.8 years) with first-time symptomatic UTI were examined scintigraphy (with an assessment of renal area involvement) and urography at the time of UTI and 1 year later. All evaluations were made blindly. Results: Of the total 314 kidneys, 80 (25%) were abnormal at initial scintigraphy. Of these 80 kidneys, 44 (55%) had normalized at follow-up. Of the 234 initially normal kidneys, 29 (12%) were abnormal at follow-up. One year after UTI, abnormalities were seen in 59 children at scintigraphy and in 18 children at urography. Renal area involvement was larger and split function abnormalities more common in kidneys that were abnormal at both scintigraphy and urography than in kidneys with only scintigraphic abnormalities. Conclusion: Quantitation of renal area involvement and split renal function at early scintigraphy would seem to be useful in identifying patients at risk of developing renal damage. Urography at 1 year after infection identified mainly those with the most severe scintigraphic abnormalities. The clinical importance of scintigraphic abnormalities that are not confirmed by urography is not known.

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: 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.