Controversies in the management of vesicoureteral reflux: The rationale for the RIVUR study

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Abstract

The current management of vesicoureteral reflux (VUR) focuses on the prevention of urinary tract infections (UTI), with curative surgery being limited to those children that fail conservative measures. This is based on the assumption that UTIs are preventable with the use of prophylatic antibiotics, leading to reduction of renal scarring, and the possibility that VUR in children can resolve spontaneously.

Methods

Review of the recent literature has demonstrated a growing concern that antibiotic prophylaxis may not lead to prevention of UTIs. Additionally, data indicate that renal scarring may not be preventable with antibiotic prophylaxis or even surgical correction of VUR. An overview of all of the current controversies is presented in this paper.

Results

Does antibiotic prophylaxis lead to reduction in UTIs in children with VUR? To address this question, the National Institutes of Health have developed a randomized placebo-controlled study of children with VUR (the RIVUR Study), identified following the development of a UTI.

Conclusions

There are far reaching consequences of the results of the RIVUR Study. If antibiotic prophylaxis does not prevent UTI in children with VUR, or lead to reduction in renal scarring, does identification of VUR provide any benefits? Perhaps appropriate treatment of UTI may be all that is necessary for preserving renal function. Final answers will have to wait until the completion of this study.

Introduction

The retrograde flow of urine from the bladder to the kidneys in children has the potential to lead to the development of pyelonephritis and secondary renal injury. Management of VUR has been based on the premise that prevention of UTIs or ablation of reflux can lead to a reduction in the potential for pyelonephritis and renal scarring. Additionally, the potential for reflux to resolve spontaneously with time in many children has led to the recommendation that initial management be limited to non-operative modalities (i.e. antibiotic prophylaxis and radiographic follow-up), with surgical treatments considered in those children that develop infections despite prophylaxis or are unable to comply with prophylaxis regimens. Most of the current recommendations were derived from studies that were limited by inadequate patient numbers and/or lack of randomization. Almost every aspect of the diagnosis and management of VUR is being re-evaluated. The Randomized Intervention for the management of VesicoUreteral Reflux (RIVUR) Study was proposed and supported by the National Institutes of Health to address some of the questions that have been raised in the management of VUR. This was designed as a multi-institutional randomized study to determine if antibiotic prophylaxis is beneficial for the prevention of UTIs in children with VUR identified following a UTI (Fig. 1).

Section snippets

Urinary tract infections

UTIs are the most frequent reason for radiographic evaluation of children to determine the presence of VUR. Such infections are seen in 2.2% of boys and 2.1% of girls younger than 2 years of age [1]. The incidence of first UTI in children younger than 6 years of age was noted to be 6.6% for girls and 1.8% for boys [2]. In a large cohort study, first UTIs were noted in 0.88% of children [3], the majority of whom were white females 2–6 years of age [3]. Only 35% of children who had a first UTI

Prevention of urinary tract infections

The primary reason for the use of antibiotic prophylaxis has been to reduce the rate of UTIs in children with VUR and therefore bring about a reduction in renal scarring. Many studies have attempted to determine if prophylaxis leads to an actual reduction in the incidence of UTIs. The initial study that attempted to address the utilization of antibiotics for the prevention of infections in VUR was conducted by Garin et al. in 2006 [42]. Children were randomized following a documented episode of

The role of dysfunctional elimination syndrome

Dysfunctional elimination is increasingly being recognized as a potential source of recurrent UTIs in children. Shaikh et al. did not find a correlation between early identification of VUR or UTI and eventual development of dysfunctional elimination syndrome [48]. Snodgrass noted a significant correlation between recurrence of UTIs and the presence of voiding dysfunction [49]. VUR was noted in 20% of girls with voiding dysfunction. Breakthrough UTIs were noted in 43% of girls with VUR who also

The role of surgical management

Improvement in surgical techniques with reduction in hospital stays made surgical correction more appealing. The introduction of endoscopic regimens has also made surgical correction more acceptable to parents. Most surgical modalities are associated with a very high potential for the correction of VUR. The benefit of the surgical management of VUR in prevention of infection and scarring continues to remain in question. The final report of the International Reflux Study indicated that at

Conclusion

The paucity of well thought-out randomized studies on VUR in children has led to continued debate on the correct algorithm for evaluation and management. The RIVUR study is recruiting a numerically appropriate cohort of children (n = 600) to answer the fundamental question in the management of VUR – does antibiotic prophylaxis lead to prevention of UTIs and secondarily renal scarring? It has been designed to overcome some of the identified problems with prior cohort studies that have purported to

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