Treatment of vesico-ureteric reflux: a new algorithm based on parental preference

Authors


N. Capozza, ‘Bambino Gesu’ Children's Hospital, Piazza S. Onofrio, 4-00165, Rome, Italy.
e-mail: capozza@opbg.net

Abstract

Authors from Rome evaluated parental preference for treatment in children with grade III VUR. Parents were provided with detailed information about the three treatment options: antibiotic treatment, open surgery, endoscopic treatment. Most parents chose endoscopic management; with this in mind, the authors proposed a new treatment algorithm for VUR.

OBJECTIVE

To assess parental preference (acknowledged in treatment guidelines as important when choosing therapy) about treatments for vesico-ureteric reflux (VUR, commonly associated with urinary tract infection and which can cause long-term renal damage if left untreated), as at present there is no definitive treatment for VUR of moderate severity (grade III).

SUBJECTS AND METHODS

The parents of 100 children with grade III reflux (38 boys and 62 girls, mean age 4 years, range 1–15) were provided with detailed information about the three treatment options available for treating VUR (antibiotic prophylaxis, open surgery and endoscopic treatment), including the mode of action, cure rate and possible complications, and the practical advantages and disadvantages. They were then presented with a questionnaire asking them to choose their preferred treatment.

RESULTS

Most parents preferred endoscopic treatment (80%), rather than antibiotic prophylaxis (5%) or open surgery (2%); 13% could not decide among the three options and endoscopic treatment was recommended.

CONCLUSION

Given the strong preference for endoscopic treatment we propose a new algorithm for treating VUR; endoscopic treatment would be considered as the first option for persistent VUR, except in severe cases where open surgery would still be recommended.

INTRODUCTION

VUR is characterized by the abnormal flow of urine from the bladder to the kidneys through the ureter. The condition, which is often congenital, affects ≈ 1% of all children [1] and is most commonly diagnosed in infancy and childhood, after repeated UTIs [2]. Based on a renal ultrasonography and voiding cysto-urethrography (VCUG), reflux can be classified into five grades (I–V) of increasing severity [3]. Mild cases of VUR are likely to resolve spontaneously with increasing age but as continuing VUR has the potential to cause long-term renal damage, early diagnosis and prevention of pyelonephritis by prophylactic antibiotic treatment are very important [4,5].

Currently, antibiotic prophylaxis is generally used as the initial therapy of grade I–III reflux [4]. Open surgery (i.e. re-implantation of the ureter into the bladder wall) is recommended for children who develop breakthrough infections despite antibiotic prophylaxis, have reflux that fails to resolve, or have reflux of grade IV or V [4,6]. Over recent years endoscopic treatment has become recognized as an alternative option for treating VUR [7]; this treatment involves injecting a bulking agent into the bladder wall to augment and elongate the intramural section of the ureter, and allow it to function correctly as a flap-valve. The role of endoscopic treatment as a standard for VUR remains to be established. The AUA guidelines do not recommend endoscopic treatment for VUR because the long-term safety and efficacy of materials used for the injection were not confirmed at the time the guidelines were reported [4]. Similarly, the European Association of Urology do not recommend endoscopic treatment for VUR because they consider that experience with the technique is not yet sufficient [6].

Given the lack of definitive treatment options for VUR, particularly VUR of moderate severity, parent and patient preferences are generally acknowledged as being crucially important in the choice of treatment. In particular, the AUA guidelines recommend that parents and patients are provided with detailed information about the available treatment options, and that their preferences are honoured when treatment is being chosen. Few data have yet been published on parental preference, although the first such study was published recently [8]. The current study was undertaken to assess informed parental preference when choosing among antibiotic prophylaxis, open surgery and endoscopic treatment for VUR.

SUBJECTS AND METHODS

Patients with grade III reflux who had received antibiotic prophylaxis for at least 6 months were selected to participate in the study. The parents were informed of the three different treatment options; documents explaining each option were provided, with details of cure rates, possible complications, and practical advantages and disadvantages, reflecting the experience within our clinic, summarized in Table 1. They were then informed that antibiotic prophylaxis does not cure VUR but prevents UTIs, thus reducing the potential for renal damage from pyelonephritis. In our clinic the treatment consists of once-daily amoxicillin (alone or combined with clavulanic acid), trimethoprim-sulphamthoxazole or cefixime. Allergic reaction is not a contraindication to continuing prophylaxis with another antibiotic. The main advantage of antibiotic prophylaxis is that it requires no invasive procedure, but persistent reflux despite long-term treatment, with a low success rate after 1 year (33% in grade II-IV reflux) is a major disadvantage. Our policy of annual assessment by VCUG, or indirect nuclear cystography in children aged > 3 years (to avoid catheterization), in accordance with internationally recognized guidelines, was also explained [4].

Table 1. A summary of the information provided to parents, to assist in the choice of a preferred method of treatment
InformationTreatment
Antibiotic prophylaxisSurgeryEndoscopic injection
MethodAmoxicillin (with or without
clavulanic acid), trimethoprim-
sulphamethoxazole, Cefixime –
once daily
Cohen cross-trigonalOne injection of Dx/HA
(a second injection after
3–4 months if needed)
Cure rates at 1 year, %33> 9571
Possible complicationsAdverse events such as nausea,
vomiting, skin-rash; occasional
serious systemic reactions
Ureteric obstruction, bleeding,
bladder dysfunction,
contralateral reflux
Postop dysuria and haematuria
(transient, for 24–48 h)
AdvantagesNoninvasive, reduces incidence
of renal damage
High success rateGood success rate, biocompatible
lack of potential for migration to
distant organs; not allergenic;
procedure repeatable
DisadvantagesPersistence of reflux despite
long-term prophylaxis, which
results in surgery; bacterial
resistance
Invasive, requires general
anaesthesia and hospitalization
of 7–10 days; risk of failure
Requires general anaesthesia and
hospitalization for up to 2 days;
risk of failure

The aim of open surgery was described to the parents as the re-creation of the valve mechanism at the vesico-ureteric junction, to prevent reflux. This option is associated with a high success rate regardless of the type of technique adopted (> 95%); the Cohen cross-trigonal technique is used in our clinic. However, because it is invasive and requires a general anaesthetic, and generally requires hospitalization for 7–10 days, it is currently limited to selected cases. Our policy of follow-up assessment at 6 months by VCUG or nuclear cystography (the latter for children aged > 3 years) was clarified.

Endoscopic treatment was also explained; this involves injecting material endoscopically into the bladder wall at the ureteric orifice, and is associated with a good success rate at 1 year (70%) depending on the degree of reflux (the protective efficacy of endoscopic treatment, based on 16 years’ experience at our clinic, indicated by lack of variation in renal status). The advantages of this treatment include repeatability and that postoperative complications are rare. The main disadvantages are that general anaesthesia and a hospital visit are required and, as for open surgery, assessment at 6 months by VCUG or nuclear cystography is recommended. Several materials have been used for endoscopic injection, including PTFE and silicone, although there are some safety concerns with both. Bovine collagen is currently used more widely, but the results are inferior to those obtained with PTFE and allergic reactions are possible. Dextranomer/hyaluronic acid (Dx/HA) copolymer is a biodegradable material that carries no risk of migration or allergic reactions, and this material is used for endoscopic treatment in our clinic. In cases of persistent VUR after two endoscopic treatments, antibiotic prophylaxis and clinical follow-up for 2 years is first recommended. In selected cases (poor compliance with antibiotic prophylaxis, breakthrough UTIs, worsening VUR, etc.), open surgery is offered.

After apparently understanding the information, the parents were issued with a questionnaire. In addition to confirming their understanding of the treatment options, the questionnaire asked whether further information would be beneficial, and third, which treatment option they would choose. The patients were then treated according to the parental preference; where no parental preference was expressed, endoscopic injection was recommended. The parents of 100 children with grade III VUR participated in the study (38 boys and 62 girls, mean age 4 years, range 1–15).

RESULTS

At the beginning of the study coexistent conditions included bladder dysfunction (11 patients, all of whom underwent bladder training and/or oxybutynin treatment) and renal scarring (18, none of whom had reduced total renal function). However, these factors did not affect the treatment options that were offered.

Over three-quarters of parents indicated their full understanding of the treatment options available; most (80%) were in favour of endoscopic treatment, with antibiotic prophylaxis being the second most popular choice (5%). In all, 13% of parents did not feel able to choose among the three options (Table 2). Parents requesting additional information were told that the 70% success rate quoted for endoscopic treatment was generic information, and that the success rate was 78% in a series of children treated with Dx/HA copolymer in our clinic. The long-term follow-up by VCUG at 28–39 months indicated that only one patient of 27 relapsed, and this was associated with voiding dysfunction that was not evident at the time of treatment. The parental preference for treatment was honoured in all cases. All children whose parents did not express a preference were treated endoscopically.

Table 2. A summary of the results of the questionnaire and the preferred treatment choice of parents
Question/response%
Did you understand the information given?
Yes78
No  5
Not completely17
Do you need additional information?
Yes52
No48
Which treatment would you choose for your child?
Open surgery  2
Endoscopic treatment80
Antibiotic prophylaxis  5
Undecided13

DISCUSSION

The evidence from this study indicates that when parents are provided with detailed information about the available treatment options, they can make an informed decision about the treatment that their child receives. Their choice was not only based upon scientific and clinical evidence, but also considered the personal effect of the treatment on their child. Parental preference clearly favoured endoscopic treatment rather than antibiotic prophylaxis or surgery (Table 2). However, the study also highlighted that even when provided with detailed information, many parents do not feel able to choose a preferred treatment, leaving the decision entirely to the clinician.

Patients with grade III reflux were chosen for the study as it is the most appropriate grade for considering all three treatment options. It is generally considered as the most severe grade for which antibiotic prophylaxis is an option, and the least severe where open surgery is likely to be considered [4]. Endoscopic treatment is also a viable option in this group of patients, so the choice of treatment was genuinely among all three options.

Although this study did not aim to compare treatment outcomes, most patients received either endoscopic treatment or antibiotic prophylaxis. We previously compared these two options in a randomized study of children aged > 1 year with VUR of grades II–IV [9]. Patients were either treated endoscopically with Dx/HA copolymer (one or two injections) or antibiotic prophylaxis for 1 year; at 1 year, 69% of patients treated endoscopically had grade I VUR bilaterally, compared with 38% of those given antibiotic prophylaxis (P = 0.029).

The present results differ slightly from those reported in a previous study of parental preference [8], as among those parents, antibiotic prophylaxis was the preferred treatment if VUR was predicted to last for < 3–4 years. A corrective procedure was preferred if VUR was predicted to last for longer than this, and endoscopic treatment was viewed as preferable to open surgery by 60% of parents. Notably, most children in the study (65%) had grade I–II and 9% had grade IV or V reflux. This could have confounded that study, as open surgery is unlikely to be offered in the mildest cases, whereas antibiotic prophylaxis would not be considered as a long-term treatment option for grade V reflux. Thus for many of the participants of that study a three-way choice among treatments was not really feasible.

The AUA guidelines recommend that parental preferences be honoured when treating VUR [4]. Although parental preference will always be influenced by the opinions of the urologist, the current findings imply that for patients in whom any of the three main treatment options could be chosen, endoscopic treatment is likely to be viewed more favourably by their parents than antibiotic prophylaxis or open surgery. This suggests a new algorithm for treating VUR, whereby patients with persistent reflux (i.e. after a trial period of antibiotic prophylaxis) should be offered endoscopic treatment as first-line therapy. Open surgery would still be recommended for patients in whom endoscopic treatment fails, and as first-line treatment for severe cases (grade IV–V). In all cases, care should be taken to ensure that parents are fully informed before the decision is made.

We anticipate that this treatment strategy would be advantageous not only in decreasing the requirement for open surgery, but also in decreasing the number of patients requiring long-term antibiotic treatment. Endoscopic treatment contrasts with open surgery in that it is minimally invasive, and may be given as an outpatient procedure, as recovery is rapid. This clearly increases the convenience for both patients and parents, and is less expensive, principally because there is no need for an overnight stay [10]. Compared with antibiotic prophylaxis, endoscopic treatment is more convenient for patients because there is no need for daily medication to be taken long-term. Widespread antibiotic prophylaxis could also encourage the development of bacterial resistance to the drugs.

The proposed reappraisal of treatment options for VUR depends on the choice of material used for endoscopic injection. Although success rates with PTFE and silicone have been high (40–90% and 82–91% after one implantation, respectively) [11] there are safety concerns with these materials, e.g. granuloma formation, migration and lack of biodegradability [11–13]. Bovine collagen has also been used for endoscopically treating VUR and although initial cure rates were similar to those obtained with PTFE and silicone (63–82% after one implantation), the long-term risk of failure make its use questionable [14]. Dx/HA copolymer is a biocompatible material developed specifically for use in this setting. Histopathological and long-term clinical data indicate that there are no safety concerns with this material, and that there is little or no risk of deterioration among children initially cured of VUR [15–17]. As a result, in our clinic we have chosen to use only Dx/HA copolymer for endoscopic treatment.

In conclusion, this study showed that parental preference strongly favours endoscopic treatment rather than open surgery or prolonged antibiotic prophylaxis for children with grade III VUR. On this basis, we propose a new treatment algorithm for VUR, with endoscopic treatment as first-line therapy for most patients with persistent reflux.

Abbreviations
VCUG

voiding cysto-urethrography

Dx/HA

dextranomer/hyaluronic acid.

Ancillary