Renal swelling indicates renal damage in infants with their first urinary tract infection.

AIM: We used ultrasound to evaluate renal swelling as a predictor of acute and permanent renal damage in infants with their first urinary tract infection (UTI). METHODS: The cohort at the Queen Silvia Children's Hospital, Gothenburg, Sweden, comprised 101 infants with their first UTI at a mean age of 3.9 ± 3.0 months. Acute and follow-up ultrasounds were carried out a few days and one month after treatment started, and a 99m technetium dimercaptosuccinic acid (DMSA) scan was carried out after one month and after a year if the first scan was abnormal. RESULTS: The acute ultrasounds showed that renal length and volume, calculated as standard deviation scores (SDS), were 1.39 ± 1.43 SDS and 1.30 ± 1.08 SDS. We found that 52% of the one-month DMSA scans and 25% of the one-year DMSA scans were abnormal. Renal length (p = 0.0026) and initial volume (p = 0.0005) on the ultrasound predicted acute renal damage at the one-month DMSA scan and initial renal length (p = 0.030) predicted permanent renal damage at the one-year DMSA scan. CONCLUSION: Renal swelling was associated with renal damage. Although the diagnostic performance compared with the DMSA scan was weak, renal swelling may help clinicians to make decisions about further investigations and follow-ups of infants with UTIs.

Ultrasound is an effective and noninvasive method of evaluating renal swelling in infants with their first urinary tract infection.

AIM: This study evaluated renal swelling in infants with a first urinary tract infection (UTI) by correlating renal length and volume with C-reactive protein (CRP) and body temperature. METHODS: Ultrasounds were carried out on 104 infants at The Queen Silvia Children's Hospital, Gothenburg, Sweden - 58 boys (mean age 3.3 months) and 46 girls (mean age 4.8 months) - during the acute phase of their UTI. A second scan was performed on 94 of them 4 weeks later. Renal length and volume were computed to standard deviation scores (SDS). RESULTS: The mean renal length and volume at the first ultrasound were 1.90 SDS (±1.54) and 1.67 SDS (±1.13) for the larger kidney and 0.86 SDS (±1.01) and 0.84 SDS (±0.90) for the smaller kidney. There was a significant decrease in renal length and volume between the two ultrasounds, with a mean difference of 0.96 SDS (±1.24) and 1.07 SDS (±1.10) for the larger kidney (p < 0.0001). The length and volume of the larger kidney correlated with CRP (p < 0.001), but only the renal length correlated with fever (p < 0.001). CONCLUSION: Early ultrasound determined renal swelling in infants with a UTI and may be a valuable noninvasive way of identifying infants with renal parenchymal involvement.

Diffusion weighted imaging is a promising method to detect acute pyelonephritis in non-sedated free breathing infants.

INTRODUCTION: Urinary tract infection (UTI) is a common disease in infants. The initial evaluation includes imaging to identify risk factors for permanent renal damage, such as malformation and renal parenchymal involvement of the infection i.e. pyelonephritis. 99mTc-Dimercaptosuccinic acid (DMSA) scintigraphy is a well-established method for detection of pyelonephritis and renal damage, but has limitations in availability, spatial resolution, and detection of congenital malformations. Diffusion weighted magnetic resonance imaging (DWI) has been shown to have a high sensitivity for detection of pyelonephritis in children without the use of invasive procedures, contrast agents or ionizing radiation. How this method performs in young infants during non-sedated free breathing remains, however, to be investigated. OBJECTIVE: To prospectively assess the feasibility and performance of DWI for detection of pyelonephritis in non-sedated free breathing infants. METHODS: 32 children <6 months of age with first-time symptomatic UTI were examined with DWI and DMSA scintigraphy. The DWI examination was performed using a free breathing protocol without the use of sedation. Pyelonephritic lesions were registered for both methods by independent observers. Agreement between DWI and DMSA was evaluated. Consensus diagnosis was determined and compared to the DWI findings. RESULTS: The MRI and DMSA examinations were completed in 25 infants, with a median age of 1.7 (0.7-5.5) months. Focal uptake reductions were detected on the DMSA images in 12 (24%) of the 50 kidneys. The DWI method demonstrated a fair to good agreement with DMSA, k = 0.50 (p < 0.0001). The consensus diagnosis was pyelonephritis in eight (16%) of the 50 kidneys. DWI detected seven of the eight kidneys with pyelonephritis. No false positive findings were detected with DWI compared to consensus diagnosis. DISCUSSION: This study has shown an agreement between DWI and DMSA scintigraphy in the detection of pyelonephritis. Further validation of the performance of DWI, using a consensus diagnosis as a reference, confirmed the potential of the method. This feasibility study included a limited number of patients and the results need to be confirmed in a prospective study of a larger cohort. CONCLUSION: Free breathing DWI is a promising method for detection of pyelonephritic lesions in non-sedated infants.

The Swedish Infant High-grade Reflux Trial - Bladder function.

INTRODUCTION: It has been suggested that infants with high-grade vesicoureteral reflux (VUR) have lower urinary tract dysfunction (LUTD) that is characterised by large bladder capacity (BC) and increased post-void residual (PVR). However, most of these infants have normal or small BC in early infancy and develop large capacity during the first year of life. OBJECTIVE: This study aimed to see whether LUTD development during the infant years in children with high-grade VUR could be prevented by early reflux resolution. MATERIALS AND METHODS: For early VUR intervention, endoscopic treatment (ET) was used in a randomised trial comprising 77 infants (55 boys) aged <8 months with VUR grade 4-5 (n = 30/n = 47); 39 were randomised to antibiotic prophylaxis and 38 to ET. Voiding cystourethrogram, free voiding observation (FVO) and renal scintigraphy were performed at baseline and after 1 year. Bladder capacity and PVR were obtained from FVO. LUTD was defined as a BC of ≥150% of expected and a PVR of ≥20 ml. RESULTS: There were no differences in bladder function variables seen between the treatment groups, despite significant differences in VUR resolution. Analysing bladder function related to VUR outcome (VUR grade ≤2 vs grade >2), independent of treatment, showed that VUR grade ≤2 was associated with a smaller BC at 1 year (P = 0.050) (a tendency already seen at baseline) and a lower PVR at baseline (P = 0.010). PVR increased from baseline to 1 year (P = 0.037) in children with grade ≤2 VUR (Summary Table). The group with persistent bilateral grade 5 VUR at 1 year had more abnormal bladder variables compared with other study subjects, with a tendency of larger BC (P = 0.057), higher PVR (P = 0.0073) and more LUTD (P = 0.029) at baseline and a larger BC at 1 year (P = 0.016). In explanatory analyses, using logistic regression, a high PVR at baseline was identified as a predictor of VUR grade >2 (P = 0.046), persistent bilateral grade 5 VUR (P = 0.022), recurrent urinary tract infection (P = 0.034), and only a tendency was seen regarding new renal damage (P = 0.053). CONCLUSION: There was no between-group difference seen in bladder function. In children with VUR resolution at follow-up, independent of treatment, BC decreased, whereas PVR increased. High PVR at baseline was a predictive factor for both non-resolution of high-grade VUR and recurrent urinary tract infection. The results suggest that LUTD cannot be prevented by early VUR resolution, but rather is an important prognostic factor for VUR outcome in both endoscopic and prophylactic treatment.

Disappearance of vesicoureteral reflux in children.

OBJECTIVE: To describe the disappearance of reflux in children with vesicoureteral reflux, in whom there are presently no population-based long-term studies. DESIGN: An unselected cohort of children with reflux detected after their first known symptomatic urinary tract infection was followed up prospectively for up to 15 years. SETTING: A single children's hospital in a distinct geographical area at which most children with symptomatic urinary tract infection were treated. PATIENTS: Two hundred thirty children--173 girls and 57 boys--with unilateral (n=130) and bilateral (n=100) reflux. Dilated reflux (grades III-V) was found in 54 patients (23.5%). The frequency of reflux was 34% in girls and 31% in boys who were examined after urinary tract infection. MAIN OUTCOME MEASURE: Disappearance of reflux. RESULTS: The probability of spontaneous disappearance of reflux was estimated using Kaplan-Meier survival curves based on 164 children who underwent multiple voiding cystourethrographies. There was a marked tendency for disappearance of reflux, with 73% of children with dilated reflux having no or only grade I reflux after 10 years. Shorter persistence of reflux was found in children with undilated reflux at the initial investigation and in boys compared with girls. However, age at first investigation was not related to the rate of disappearance, and there was no difference between children with bilateral compared with unilateral reflux. CONCLUSIONS: This study of an unselected group of children with urinary tract infection shows a favorable long-term outcome concerning disappearance of reflux. In children with dilated reflux, this tendency was more pronounced than previously reported.

Renal function 16 to 26 years after the first urinary tract infection in childhood.

OBJECTIVE: To evaluate renal function in a population-based cohort with urographic renal scarring after childhood urinary tract infection (UTI). DESIGN: Follow-up investigation 16 to 26 years after the first recognized UTI. SETTING: Outpatient university clinic for children with UTI serving the local area. PATIENTS: From the original cohort of 1221 consecutive children with first UTI diagnosed during 1970 to 1979, 57 (41 females and 16 males; mean age, 24.5 years) of 68 with nonobstructive renal scarring participated as well as 51 (38 females and 13 males; mean age, 24.9 years) matched subjects without scarring. MAIN OUTCOME MEASURE: Glomerular filtration rate (GFR) measured by chromium 51-EDTA clearance, expressed as milliliters per minute per 1.73 square meters. RESULTS: Median GFR was 99 in both those with and without renal scarring. In patients with unilateral scarring, the total GFR remained unchanged over the years whereas the individual GFR of the scarred kidneys declined significantly from 46 to 39. In 7 patients with bilateral scarring, the GFR declined from 94 to 84 (P = .14); compared with those with unilateral scarring, the GFR was significantly lower at follow-up (P = .007). Median urinary albumin-creatinine ratio was 1.2 and 0.6 mg/mmol in those with scarring and those without, respectively (P = .30). CONCLUSIONS: The GFR 2 decades after the first recognized UTI in childhood was well preserved. However, a significant reduction of individual renal GFR in the unilaterally scarred kidneys indicates that further follow-up is required. Although there were few patients with bilateral scarring, a more serious prognosis can be expected among them.

The natural history of bacteriuria in childhood.

Urinary tract infections are common during infancy and childhood but are easily overlooked because of the unspecific symptoms. Prevention of renal scarring and its potential long-term consequences is possible but requires an increased awareness of the diagnosis, the imaging revealing anomalies within the urinary tract, and the long-term supervision. This should include any possibility of the child having pyelonephritic recurrences, which should be treated without delay; however, asymptomatic bacteriuria in infants and children is an innocent condition and screening is not recommended.

Scoliosis in Rett syndrome. Clinical and biological aspects.

STUDY DESIGN: The natural history of progression of scoliosis was studied. The authors included a wide range of ages and correlated progression and progression rate to both age of the patient and the neurobiologic staging of the disease. OBJECTIVES: The authors studied information compiled by Hagberg and coworkers regarding Rett syndrome. The total number of patients was 78, with age ranging from 1 to 34 years. Standing or sitting anteroposterior roentgenograms were collected and measured. METHOD: The material was studied initially separately regarding orthopedic and radiologic analysis on one hand and neurobiologic staging on the other. Radiographic films were measured both retrospectively and prospectively, and scoliosis angle and progression and progression rate was calculated. Staging of patients with Rett syndrome was done according to Hagberg. RESULTS: When correlating curve magnitude and progression, the authors found that patients progressing > 15 degrees/year were classified as IV-A or IV-B stages. In the 0-5 year group, of the patients already having a curve of 15 degrees or more, all but one rapidly progressed to stage IV. The ten worst cases were characterized by early hypotonia, weakness, and gross motor disturbance. CONCLUSIONS: The scoliosis in Rett syndrome is of a neurogenic type, and it develops earlier than idiopathic scoliosis. The development of scoliosis is dependent more on stage of disease than on age. Curve progression is usually more rapid than in idiopathic scoliosis and in most other types of neurogenic scoliosis in childhood and occurs in a broader age span. Early hypotonia, weakness, and muscular insufficiency, and an early clinical referral to disease stages IV-A or IV-B are ominous factors. Clinical follow-up should begin early and be repeated regularly and frequently.

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.

Six year follow up of infants with bacteriuria on screening.

OBJECTIVE: To determine the value of screening for bacteriuria in infants with special emphasis on the natural course of untreated asymptomatic bacteriuria, renal growth, and renal damage. DESIGN: Prospective six year follow up of infants with bacteriuria on screening in an unselected infant population. SETTING: Paediatric outpatient clinic. PATIENTS: 50 Infants (14 girls, 36 boys) with bacteriuria on screening verified by suprapubic aspiration from an unselected population of 3581 infants in a defined area of Gothenburg. INTERVENTIONS: Children with asymptomatic bacteriuria and normal findings on initial urography were untreated, although other infections were treated. MAIN OUTCOME MEASURES: Culture of urine and determination of C reactive protein concentration every six weeks for the first six months after diagnosis, every three months from six months to two years, and every six months between two and three years; thereafter yearly urine culture. Evaluation of renal concentrating capacity with a desmopressin test; radiological examination, including first and follow up urography and micturition cystourethrography without antibiotic cover; and measurement of renal parenchymal thickness and renal surface area. RESULTS: Of the original 50 infants, 37 (12 girls, 25 boys) were followed up for at least six years. Two infants developed pyelonephritis within two weeks after bacteriuria was diagnosed; the others remained free of symptoms. 45 Infants were untreated; the bacteriuria cleared spontaneously in 36 and in response to antibiotics given for infections in the respiratory tract in eight. Recurrences of bacteriuria were observed in 10 of the 50 children, of whom one had pyelonephritis. No child had more than one recurrence. At follow up urography in 36 of the 50 children (9 girls, 27 boys) after a median of 32 months no child had developed renal damage. First samples tested for renal concentrating capacity showed significantly higher values than those from a reference population (mean SD score 0.50, 95% confidence interval 0.21 to 0.79; p less than 0.001), but the last samples showed no significant difference (mean SD score 0.08, -0.24 to 0.40; p greater than 0.05). CONCLUSIONS: Mass screening for bacteriuria in infancy results primarily in detection of innocent bacteriuric episodes and is not recommended.

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 were unaware 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 diagnostic criterion 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.

Assessment of infective urinary tract disorders.

Urinary tract infection (UTI) is common in children, particularly in the youngest age groups. There is a risk for progressive deterioration of renal function in these children if aggravating factors such as gross reflux and/or outflow obstruction of the urinary tract are present. In this review the pros and cons of available scintigraphic and radiological imaging techniques for the work-up of these children are presented. Ultrasound can be used in the acute phase to exclude obstruction but can not reliably show transient or permanent parenchymal lesions. The presence of reflux can be established with X-ray or direct nuclide cystography. The X-ray technique gives good morphological information and has a grading system with prognostic relevance. Both techniques are invasive and great care must be taken to keep the radiation burden down with the X-ray technique. Indirect nuclide cystography following a renographic study is non-invasive but has a lower sensitivity than direct techniques. More experience is needed with the indirect technique to evaluate the consequences of its apparently low sensitivity. Urography has a limited place in the acute work-up of urinary tract infection but can be used to look for renal scarring 1-2 years after an acute pyelonephritis. The 99mTc dimercaptosuccinic acid (DMSA) scan can be used during the acute UTI to show pyelonephritic lesions with good accuracy and/or during the follow-up after six months to show permanent lesions. The acute DMSA scan can be omitted. An early treatment is more important than an early scan!

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 children's 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.

Renal damage one year after first urinary tract infection: role of dimercaptosuccinic acid scintigraphy.

OBJECTIVE: The aim of this study was to determine whether age, C-reactive protein (CRP), body temperature, or results of voiding cystourethrography at diagnosis of first-time symptomatic urinary tract infection could predict the risk of renal damage as evaluated by dimercaptosuccinic acid (DMSA) scintigraphy performed 1 year after the infection. DESIGN: The study included 157 children (median age, 0.4 year, range, 5 days to 5.8 years) with first-time symptomatic urinary tract infection. In children 1 year of age or older, a body temperature of 38.5 degrees C or higher was necessary for inclusion. CRP and body temperature were measured at the time of infection, and voiding cystourethrography was performed shortly thereafter. DMSA scintigraphy was performed 1 year later in all children. RESULTS: After 1 year, 59 (38%) of the 157 children had renal damage as evaluated by DMSA scintigraphy, and of these, 28 (47%) had reflux. There was a positive correlation between renal damage and CRP, body temperature, and reflux. Children with high levels of CRP, high fever, and dilating reflux had a risk of renal damage up to 10 times higher than children with normal or slightly elevated CRP levels, no or mild fever, and no reflux. CONCLUSION: CRP concentration and body temperature at the index infection, in combination with the results of voiding cystourethrography, are useful in classifying children at high and low risk of scintigraphic renal damage 1 year after urinary tract infection.

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.

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.

Selective use of excretory urography in women with acute pyelonephritis.

The outcome of excretory urography was analyzed in 103 nonpregnant women followed prospectively after community acquired acute pyelonephritis. Radiological abnormality was found in 40 per cent of the patients (17 per cent had major abnormalities, including renal scarring, calculi and obstruction). All 5 women with surgically correctable lesions had rapid bacteriological relapse or recurrent acute pyelonephritis. Neither a history of urinary tract infection, the acute inflammatory response nor infection due to Escherichia coli with or without adhesins specific for Gal alpha 1----4Gal beta-containing receptors was efficient in predicting major radiographic lesions or the outcome of treatment. Bacteremia was detected in 27 per cent of the patients but in the absence of obstruction. These results suggest that excretory urography is dispensable in most women with acute pyelonephritis, and that those needing such investigation may be identified by failure to respond to antibiotic treatment or by the recurrence pattern.

Virulence of Escherichia coli in relation to host factors in women with symptomatic urinary tract infection.

The relationship between bacterial characteristics and the severity of urinary tract infection in adults has not been clarified. In this study, Escherichia coli strains (n = 178) were prospectively collected from women with community-acquired urinary tract infection. The isolates were identified by O:K:H serotype and characterized for adherence, hemolysin production, and serum bactericidal resistance. The patients had acute pyelonephritis with or without complicating factors and acute cystitis. Nine serotypes (O1:K1:H7, O1:K1:H-, O2:K1:H-, O4:K12:H1, O7:K1:H-, O9:K34:H-, O16:K1:H6, O16:K1:H-, and O75:K5:H-) comprised 65% of the strains in uncomplicated pyelonephritis, but were significantly less often encountered in complicated pyelonephritis or cystitis. Adherence was the single property most characteristic of the pyelonephritogenic clones. Adhesins specifically recognizing Gal alpha 1----4Gal beta-containing receptors occurred in 80% of strains in uncomplicated pyelonephritis, in 50% of strains in complicated infections, and in 37% of cystitis strains. Hemolysin production and serum resistance did not correlate with any disease pattern. Advanced age did not seem to reduce the selection of virulent E. coli to cause pyelonephritis. These results demonstrate in women a relationship between E. coli virulence and the severity of urinary tract infection analogous to that previously observed in pediatric populations and also illustrate the balance between host resistance and bacterial virulence in the urinary tract.