Conflicting views of physicians and surgeons concerning pediatric urinary tract infection: a comparative review.

BACKGROUND: A first febrile urinary tract infection (UTI) is a common condition in children, and pathways of management have evolved over time. OBJECTIVE: To determine the extent to which pediatricians and surgeons differ in their investigation and management of a first febrile UTI, and to evaluate the justifications for any divergence of approach. MATERIALS AND METHODS: A literature search was conducted for papers addressing investigation and/or management following a first febrile UTI in children published between 2011 and 2021. Searches were conducted on Medline, Embase, and the Cochrane Controlled Trials Register. To be eligible for inclusion, a paper was required to provide recommendations on one or more of the following: ultrasound (US) and voiding cystourethrogram (VCUG), the need for continuous antibiotic prophylaxis and surgery when vesicoureteral reflux (VUR) was detected. The authorship required at least one pediatrician or surgeon. Authorship was categorized as medical, surgical, or combined. RESULTS: Pediatricians advocated less imaging and intervention and were more inclined to adopt a "watchful-waiting" approach, confident that any significant abnormality, grades IV-V VUR in particular, should be detected following a second febrile UTI. In contrast, surgeons were more likely to recommend imaging to detect VUR (p<0.00001), and antibiotic prophylaxis (p<0.001) and/or surgical correction (p=0.004) if it was detected, concerned that any delay in diagnosis and treatment could place the child at risk of kidney damage. Papers with combined authorship displayed intermediate results. CONCLUSION: There are two distinct directions in the literature regarding the investigation of an uncomplicated first febrile UTI in a child. In general, when presented with a first febrile UTI in a child, physicians recommend fewer investigations and less treatment, in contrast to surgeons who advocate extensive investigation and aggressive intervention in the event that imaging detects an abnormality. This has the potential to confuse the carers of affected children.

Vesico-ureteric reflux in children and young people undergoing kidney transplantation.

Vesico-ureteric reflux (VUR) into transplanted kidneys in children and young people is a common occurrence, found in 19 to 60% of those who had an anti-reflux procedure and up to 79% in the absence of such a procedure. While VUR is unlikely to be of concern without evidence of symptomatic urinary tract infections, less certainty exists regarding outcomes when the VUR is associated with urinary tract infection (UTI) and transplant pyelonephritis. Issues explored will include additional risk factors that might predispose to UTI, any effect of pyelonephritis on acute and long-term kidney allograft function and practical strategies that may reduce the prevalence of infection.

Kidney damage associated with vesico ureteric reflux.

PURPOSE OF REVIEW: The aim of this review is to highlight the most recent developments in the understanding of kidney damage associated with vesico ureteral reflux. The severe damage, with major adverse long-term sequelae, was thought to be, for the most part, the result of pyelonephritis, predisposed to by vesico ureteral reflux. RECENT FINDINGS: It is now recognized that there are two distinct forms of kidney damage (congenital and acquired), in association with reflux. We examined the most recent research regarding these two conditions. SUMMARY: The most recent articles focus on an understanding and the possible interventions for the congenital and acquired abnormalities of the kidney, associated with reflux. Of particular interest in congenital disorders, is the importance of urothelium and gene mutations in normal and aberrant development of the urinary tract. As regards the predisposition to urinary tract infections and kidney scarring, the importance of uromodulin in the defence mechanism preventing infection, and the role of interventions aimed at reducing scarring, such as vitamin A and steroids during the acute phase of the infection, are discussed. A recent article of particular value demonstrated the absence of long-term adverse outcomes during pregnancy, in women investigated for urinary tract infections in childhood.

Antibiotic Prophylaxis for Urinary Tract Infection-Related Renal Scarring: A Systematic Review.

CONTEXT: Acute pyelonephritis may result in renal scarring. Recent prospective studies have shown a small benefit of antibiotic prophylaxis in preventing symptomatic and febrile urinary tract infections (UTIs), while being underpowered to detect any influence in prevention of renal damage. OBJECTIVES: Review of the literature and a meta-analysis to evaluate the effect of antibiotic prophylaxis on UTI-related renal scarring. DATA SOURCES: Medline, Embase, and Cochrane Controlled Trials Register electronic databases were searched for studies published in any language and bibliographies of identified prospective randomized controlled trials (RCTs) performed and published between 1946 and August 2016. STUDY SELECTION: Subjects 18 years of age or younger with symptomatic or febrile UTIs, enrolled in prospective RCTs of antibiotic prophylaxis where 99mTc dimercaptosuccinic acid scans were performed at entry into the study and at late follow-up to detect new scar formation. DATA EXTRACTION: The literature search, study characteristics, inclusion and exclusion criteria, and risk of bias assessment were independently evaluated by 2 authors. RESULTS: Seven RCTs (1427 subjects) were included in the meta-analysis. Our results show no influence of antibiotic prophylaxis in preventing renal scarring (pooled risk ratio, 0.83; 95% confidence interval, 0.55-1.26) as did a subanalysis restricted to those subjects with vesicoureteral reflux (pooled risk ratio, 0.79; 95% confidence interval, 0.51-1.24). LIMITATIONS: Limitations include the small number of studies, short duration of follow-up, and insufficient children with high-grade dilating reflux and/or renal dysplasia enrolled in the studies. CONCLUSIONS: Antibiotic prophylaxis is not indicated for the prevention of renal scarring after a first or second symptomatic or febrile UTI in otherwise healthy children.

Different guidelines for imaging after first UTI in febrile infants: yield, cost, and radiation.

OBJECTIVE: To evaluate the yield, economic, and radiation costs of 5 diagnostic algorithms compared with a protocol where all tests are performed (ultrasonography scan, cystography, and late technetium(99)dimercaptosuccinic acid scan) in children after the first febrile urinary tract infections. METHODS: A total of 304 children, 2 to 36 months of age, who completed the diagnostic follow-up (ultrasonography, cystourethrography, and acute and late technetium(99)dimercaptosuccinic acid scans) of a randomized controlled trial (Italian Renal Infection Study 1) were eligible. The guidelines applied to this cohort in a retrospective simulation were: Melbourne Royal Children's Hospital, National Institute of Clinical Excellence (NICE), top down approach, American Academy of Pediatrics (AAP), and Italian Society of Pediatric Nephrology. Primary outcomes were the yield of abnormal tests for each diagnostic protocol; secondary outcomes were the economic and radiation costs. RESULTS: Vesicoureteral reflux (VUR) was identified in 66 (22%) children and a parenchymal scarring was identified in 45 (15%). For detection of VUR (47/66) and scarring (45/45), the top down approach showed the highest sensitivity (76% and 100%, respectively) but also the highest economic and radiation costs (€52 268. 624 mSv). NICE (19/66) and AAP (18/66) had the highest specificities for VUR (90%) and the Italian Society of Pediatric Nephrology had the highest specificity (20/45) for scars (86%). NICE would have been the least costly (€26 838) and AAP would have resulted in the least radiation exposure (42 mSv). CONCLUSIONS: There is no ideal diagnostic protocol following a first febrile urinary tract infection. An aggressive protocol has a high sensitivity for detecting VUR and scarring but carries high financial and radiation costs with questionable benefit.

Pediatric febrile urinary tract infections: the current state of play.

Studies undertaken in recent years have improved our understanding regarding the consequences and management of febrile urinary tract infections (UTIs), which are amongst the most common serious bacterial infections in childhood, with renal scarring a frequent outcome. In the past pyelonephritic scarring of the kidney, often associated with vesico-ureteral reflux (reflux nephropathy) was considered a frequent cause of chronic renal insufficiency in children. Increasing recognition as a consequence of improved antenatal ultrasound, that the majority of these children had congenital renal hypo-dysplasia, has resulted in a number of studies examining treatment strategies and outcomes following UTI. In recent years there is a developing consensus regarding the need for a less aggressive therapeutic approach with oral as opposed to intravenous antibiotics, and less invasive investigations, cystourethrography in particular, following an uncomplicated first febrile UTI. There does remain a concern that with this newer approach we may be missing a small subgroup of children more prone to develop severe kidney damage as a consequence of pyelonephritis, and in whom some form of intervention may prove beneficial. These concerns have meant that development of a universally accepted diagnostic protocol remains elusive.

Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized, controlled, noninferiority trial.

OBJECTIVES: Febrile urinary tract infections are common in children and associated with the risk for renal scarring and long-term complications. Antimicrobial prophylaxis has been used to reduce the risk for recurrence. We performed a study to determine whether no prophylaxis is similar to antimicrobial prophylaxis for 12 months in reducing the recurrence of febrile urinary tract infections in children after a first febrile urinary tract infection. METHODS: The study was a controlled, randomized, open-label, 2-armed, noninferiority trial comparing no prophylaxis with prophylaxis (co-trimoxazole 15 mg/kg per day or co-amoxiclav 15 mg/kg per day) for 12 months. A total of 338 children who were aged 2 months to <7 years and had a first episode of febrile urinary tract infection were enrolled: 309 with a confirmed pyelonephritis on a technetium 99m dimercaptosuccinic acid scan with or without reflux and 27 with a clinical pyelonephritis and reflux. The primary end point was recurrence rate of febrile urinary tract infections during 12 months. Secondary end point was the rate of renal scarring produced by recurrent urinary tract infections on technetium 99m dimercaptosuccinic acid scan after 12 months. RESULTS: Intention-to-treat analysis showed no significant differences in the primary outcome between no prophylaxis and prophylaxis: 12 (9.45%) of 127 vs 15 (7.11%) of 211. In the subgroup of children with reflux, the recurrence of febrile urinary tract infections was 9 (19.6%) of 46 on no prophylaxis and 10 (12.1%) of 82 on prophylaxis. No significant difference was found in the secondary outcome: 2 (1.9%) of 108 on no prophylaxis versus 2 (1.1%) of 187 on prophylaxis. Bivariate analysis and Cox proportional hazard model showed that grade III reflux was a risk factor for recurrent febrile urinary tract infections. Whereas increasing age was protective, use of no prophylaxis was not a risk factor. CONCLUSIONS: For children with or without primary nonsevere reflux, prophylaxis does not reduce the rate of recurrent febrile urinary tract infections after the first episode.

Early treatment of acute pyelonephritis in children fails to reduce renal scarring: data from the Italian Renal Infection Study Trials.

OBJECTIVES: The American Academy of Pediatrics recommendation for febrile infants and young children suspected of having a urinary tract infection is early antibiotic treatment, given parenterally if necessary. In support of this recommendation, data suggesting that delay in treatment of acute pyelonephritis increases the risk of kidney damage are cited. Because the risk was not well defined, we investigated renal scarring associated with delayed versus early treatment of acute pyelonephritis in children. METHODS: The research findings are derived from 2 multicenter, prospective, randomized, controlled studies, Italian Renal Infection Study 1 and 2, whose primary outcomes dealt with initial antibiotic treatment and subsequent prophylaxis, respectively. From the 2 studies, we selected the 287 children with confirmed pyelonephritis on acute technetium-99m-dimercaptosuccinic acid scans who underwent repeat scanning to detect scarring 12 months later. The children were 1 month to <7 years of age when they presented with their first recognized episode of acute pyelonephritis in northeast Italy. RESULTS: Progressive delay in antibiotic treatment of acute pyelonephritis from <1 to >/=5 days after the onset of fever was not associated with any significant increase in the risk of scarring on technetium-99m-dimercaptosuccinic acid scans obtained 1 year later. The risk of scarring remained relatively constant at 30.7 +/- 7%. Clinical and laboratory indices of inflammation were comparable in all groups, as was the incidence of vesicoureteric reflux. CONCLUSIONS: Early treatment of acute pyelonephritis in infants and young children had no significant effect on the incidence of subsequent renal scarring. Furthermore, there was no significant difference in the rate of scarring after acute pyelonephritis when infants and young children were compared with older children.