Controversies in the management of vesicoureteral reflux: The rationale for the RIVUR 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
References (56)
- et al.
Procalcitonin to reduce the number of unnecessary cystographies in children with a urinary tract infection: a European validation study
J Pediatr
(2007) - et al.
Relationship among vesicoureteral reflux, urinary tract infection and renal damage in children
J Urol
(2007) - et al.
The role of vesicoureteral reflux in acute renal cortical scintigraphic lesion and ultimate scar formation
J Urol
(2008) - et al.
Risk of renal scarring in vesicoureteral reflux detected either antenatally or during the neonatal period
Urology
(2003) - et al.
99m Technetium dimercapto-succinic acid renal scintigraphy abnormalities in infants with sterile high grade vesicoureteral reflux
J Urol
(2000) - et al.
Prevalence of hypertension in children with primary vesicoureteral reflux
J Pediatr
(1993) - et al.
Morphological characteristics of segmental renal scarring in vesicoureteral reflux
J Urol
(1992) - et al.
Interaction of multiple risk factors in the pathogenesis of experimental reflux nephropathy in the pig
J Urol
(1985) - et al.
Does urinary tract ultrasonography at hospitalization for acute pyelonephritis predict vesicoureteral reflux?
J Urol
(2001) - et al.
Uroradiologic evaluation of children with urinary tract infection: are both ultrasonograpy and renal cortical scintigraphy necessary?
J Pediatr
(1995)
Febrile urinary tract infections in infants: renal ultrasound remains necessary
J Urol
Dimercapto-succinic acid scintigraphy instead of voiding cystourethrography for infants with urinary tract infection
J Urol
Does a normal DMSA obviate the performance of voiding cystourethrography in evaluation of young children after their first urinary tract infection?
Int J Pediatr
Antibiotic prophylaxis for the prevention of recurrent urinary tract infection in children with low grade vesicoureteral reflux: results from a prospective randomized study
J Urol
Relationship of voiding dysfunction to urinary tract infection and vesicoureteral reflux in children
Urology
Failure of subureteral bovine collagen injection for the endoscopic treatment of primary vesicoureteral reflux in long-term follow-up
Urology
A new bioimplant for the endoscopic treatment of vesicoureteral reflux: experimental and short-term clinical results
J Urol
Febrile urinary tract infections in children with an early negative voiding cystourethrogram after treatment of vesicoureteral reflux with dextranomer/hyaluronic acid
J Urol
Minimum incidence and diagnostic rate of first urinary tract infection
Pediatrics
Incidence rate of first-time symptomatic urinary tract infection in children under 6 years of age
Acta Paediatr
Recurrent urinary tract infections in children: risk factors and association with prophylactic antimicrobials
JAMA
First urinary tract infection in neonates, infants and young children: a comparative study
Pediatr Nephrol
The relationship between urinary tract infections and vesicoureteral reflux in Turkish children
Int Urol Nephrol
Prediction of vesico-ureteric reflux in childhood urinary tract infection: a multivariate approach
Acta Paediatr
Prediction of vesicoureteral reflux after a first febrile urinary tract infection in children: validation of a clinical decision rule
Arch Dis Child
Procalcitonin as a predictor of vesicoureteral reflux in children with a first febrile urinary tract infection
Pediatrics
Predictive risk factors for chronic renal failure in primary high-grade vesico-ureteric reflux
BJU Int
Predictors of renal scar in children with urinary infection and vesicoureteral reflux
Pediatr Nephrol
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Phenolic acid content and antiadherence activity in the urine of patients treated with cranberry syrup (Vaccinium macrocarpon) vs. trimethoprim for recurrent urinary tract infection
2015, Journal of Functional FoodsCitation Excerpt :It has been recommended (American Academy of Pediatrics, Committee on Quality Improvement Subcommittee on Urinary Tract Infection, 1999) that all cases of UTI in children aged two months to two years, after antibiotic treatment for a period of 7–14 days, should be treated with antibiotics until imaging studies are completed. However, later evidence (Garin et al., 2006; Mathews et al., 2009) suggests that antibiotic prophylaxis does not reduce renal scarring, even in patients with high-grade reflux, and so its usefulness has been questioned. Other studies (Craig et al, 2009) have shown that paediatric patients with recurrent UTI who are treated with trimethoprim-sulphamethoxazole at low doses experienced a 6% reduction in the risk of UTI compared with a placebo group (95% CI: 1–11).
The Robotic-assisted Ureteral Reimplantation: The Evolution to a New Standard
2015, Urologic Clinics of North AmericaCitation Excerpt :However one of the earliest large series of RAL extravesical ureteral reimplantations in 2008 reported success equivalent to those generally expected by the open technique.12 As demonstrated herein, the use of the RAL surgery has made the repair of vesicoureteral reflux a viable approach in comparison with antibiotic prophylaxis, even as the potential adverse events are mitigated by improved magnification and focused dissection.9,14,19 For vesicoureteral reflux (VUR), indications for treatment include recurrent pyelonephritis/febrile UTIs, worsening hydronephrosis/parenchymal thinning, worsening function on renal scan, and desire by parents to come off of prophylactic antibiotics.
Childhood vesicoureteral reflux studies: Registries and repositories sources and nosology
2013, Journal of Pediatric UrologyCitation Excerpt :An ideal study should obtain urine by bladder catheterization or suprapubic aspiration in non-toilet-trained children [5,8,9] rather than sterile-bag urine collection [4,10–12], an opinion also expressed by Hoberman and Keren [1]. Another issue can be insufficient statistical power to detect clinically important differences: in order to detect a reduction in the absolute risk of recurrent UTI of 10%, a study would need to enroll roughly 600 children [1,23]. Several of these registries have fewer than 300 patients enrolled (Tables 1 and 2).
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The Randomized Intervention for the Management of Vesicoureteral Reflux (RIVUR) Study, Funded by the NIH/NIDDK.