Background
The management of affected children has been directed at preventing infection and permanent renal parenchymal damage and its late complications by antibiotic prophylaxis and/or surgical correction of reflux. However, controversy remains regarding the optimal strategies for management of children with primary vesicoureteric reflux (VUR).
Classification
In 1985, the International Reflux Study Committee introduced a uniform system for the classification of VUR (see Table below). The grading system combines two earlier classifications and is based upon the extent of retrograde filling and dilatation of the ureter, the renal pelvis and the calyces on a voiding cystourethrography (VCUG). The Committee also described a standardized technique of VCUG to allow comparability of results.
Table. Grading System for Vesicoureteric Reflux, According to the International Reflux Study Committee
| Grade I |
Reflux does not reach the renal pelvis; varying degrees of ureteral dilatation |
| Grade II |
Reflux reaches the renal pelvis; no dilatation of the collecting system; normal fornices |
| Grade III |
Mild or moderate dilatation of the ureter, with or without kinking; moderate dilatation of the collecting system; normal or minimally deformed fornices |
| Grade IV |
Moderate dilatation of the ureter with or without kinking; moderate dilatation of the collecting system; blunt fornices, but impressions of the papillae still visible |
| Grade V |
Gross dilatation and kinking of the ureter, marked dilatation of the collecting system; papillary impressions no longer visible; intraparenchymal reflux |
Diagnostic Work-up
A basic diagnostic work-up comprises a detailed medical history (including family history), physical examination, urinalysis, urine culture and, if renal function needs to be assessed, serum creatinine level. Diagnostic imaging for VUR encompasses both radiological and sonographic modalities. Radiological modalities comprise VCUG, the most widespread method for examination of reflux, and radionuclide cystography (RNC).
In RNC, radiation exposure is significantly lower than in VCUG with continuous fluoroscopy, but the anatomical details depicted are much more inferior. With the introduction of pulsed fluoroscopy, the radiation exposure of VCUG could be markedly reduced. The use of VCUG allows the grade of reflux to be determined (in a single or duplicated kidney) and the assessment of bladder and ureteral configuration. Moreover, VCUG is the study of choice for imaging the urethra. The sonographic diagnosis of VUR with intravesical administration of an ultrasound (US) contrast agent (voiding urosonography [VUS]) is mostly used as the primary reflux examination modality in girls and during follow-up.
In complex cases, magnetic resonance urography may be required for evaluation of the upper urinary tract.
Dimercaptosuccinic acid (DMSA) is the best nuclear agent for visualizing cortical tissue, evaluating renal parenchyma, and documenting the presence of renal scars. Children with normal DMSA during an acute urinary tract infection (UTI) have a low risk of renal damage. Children with normal follow-up DMSA and low-grade VUR have more frequent spontaneous resolution of VUR.
In the case of incontinence or residual urine, urodynamic studies can be performed to reveal functional abnormalities of the lower urinary tract. Such testing is most important in patients in whom secondary reflux is suspected, such as patients with spina bifida or boys whose VCUG is suggestive of residual posterior urethral valves. Yet, in most cases of non-neurogenic voiding dysfunction, diagnosis and follow-up can be limited to non-invasive tests (voiding charts, US, uroflowmetry). In the few remaining children with inconclusive findings and who are refractory to treatment, urodynamic tests are necessary. Appropriate management of voiding dysfunction will often result in the resolution of reflux.
In the past, cystoscopy was considered to be essential for the assessment of VUR. The position and shape of the ureteral orifices were thought to correlate with the grade and prognosis. Subsequent data have demonstrated that cystoscopic observations do not contribute significantly to the outcome of management. Cystoscopy may be performed at the time of open surgery to identify additional anatomical abnormalities, such as ureteral duplication and ureteral ectopia.
Treatment
Early diagnosis and vigilant monitoring are the cornerstones of treatment (see the table below). The ultimate objective of treatment is to allow normal renal growth and to prevent permanent renal parenchymal damage and its late complications (reflux nephropathy, see the original guideline document). There is no single therapeutic strategy for all clinical settings of VUR.
Therapeutic options comprise conservative (medical) management, including antibiotic prophylaxis, and interventional approaches (i.e., endoscopic subureteral injection, laparoscopic or open surgical correction of reflux), in isolation or combined.
The individual choice of management is based on the presence of renal scars, the clinical course, grade of reflux, ipsilateral renal function, bilaterality, bladder capacity and function, associated anomalies of the urinary tract, age, compliance and parental preference.
Surgical correction is warranted in recurrent febrile infections despite antibiotic prophylaxis (breakthrough infections), medical non-compliance, and new scars and in the presence of associated malformations (e.g., duplex systems, Hutch diverticulum, ectopic ureter).
In secondary VUR, the objective of management is treatment of the underlying condition. If VUR persists after successful therapy of the underlying condition, further management depends on the individual clinical setting.
Table. Treatment of Reflux
| Patient's Age |
Grade of Reflux/Gender |
Management |
| <1 year |
|
Conservative |
| 1-5 year(s) |
Grade I-III |
Conservative |
| |
Grade IV-V |
Surgical correction |
| >5 years |
Boys |
Indication for surgery is rare |
| |
Girls |
Surgical correction |
Conservative Approach
The rationale for conservative management is the observation that VUR can resolve spontaneously with time, mostly in young patients with low-grade reflux (81% and 48% in VUR grades I-II and III-V, respectively). The objective of conservative therapy is prevention of febrile UTI.
Education and consistent follow-up of the patient and parent, high fluid intake, regular and complete emptying of the bladder (if necessary with double micturition) and low-dose antibiotic prophylaxis are key aspects of conservative management. In boys with low-grade VUR, circumcision may be advised.
Conservative management should be dismissed in favour of surgical intervention in all cases of febrile breakthrough infections, as well as in girls in whom VUR has persisted up to an age at which spontaneous resolution can no longer be expected. In boys 5 years and older antibiotic prophylaxis may be stopped, and indications for surgical reflux correction are rare.
Interventional Therapy
Open Surgery
Various intra- and extra-vesical techniques have been described for the surgical correction of reflux. Although different methods have specific advantages and complications, they all share the basic principle of lengthening the intramural part of the ureter by submucosal embedding of the ureter. All techniques have been shown to be safe with a low rate of complications and excellent success rates (92%-98%). Currently, the most popular procedures are the Lich-Gregoir, Politano-Leadbetter, Cohen and Psoas-Hitch ureteroneocystostomy.
Surgery in early infancy carries a high risk of severely damaging bladder function. If an extravesical procedure is planned, cystoscopy should be performed preoperatively to assess the bladder mucosa and position and configuration of the ureteric orifices. In bilateral reflux, intravesical antireflux procedures may be considered, as simultaneous bilateral extravesical reflux repair carries an increased risk of temporary postoperative urine retention.
Laparoscopic Reflux Correction
In a small number of children, VUR has been corrected laparoscopically. Although success rates are similar to open surgery, laparoscopic reflux correction takes significantly longer and therefore has no obvious advantages. At present, a laparoscopic approach cannot be recommended as a routine procedure.
Endoscopic Therapy
Although still mainly experimental, endoscopic treatment of VUR offers the advantage of enabling treatment of the underlying anatomical defect while avoiding the morbidity of open surgery. With the availability of biodegradable substances, endoscopic subureteral injection of tissue-augmenting substances (bulking agents) have become an alternative to long-term antibiotic prophylaxis and surgical intervention in the treatment of VUR in children. Although there is not yet a prospective trial proving that endoscopic therapy is equally effective as the conservative management, endoscopic therapy is currently being used as the initial treatment of reflux in some centres. A sound clinical validation of its effectiveness is currently hampered by the lack of methodologically appropriate studies.
Follow-up
Follow-up after surgical correction of VUR is a controversial issue. In a recent update of the International Reflux Study, the authors published the results of urography at 10 years after either medical or surgical treatment of VUR. They concluded that with careful management, only a small proportion of children with severe reflux developed new scars and then rarely after the first 5-year follow-up period, and that there was no difference between children treated medically or surgically. Routine radionuclide studies are therefore not recommended.
As post-operative VCUG does not allow identification of children at risk of developing febrile UTI, this investigation is optional. Although VCUG may not be necessary in clinically asymptomatic cases after open surgery, it is mandatory following endoscopic treatment.
Obstruction of the upper urinary tract is ruled out by sonography at discharge and 3 months postoperatively. The follow-up protocol should include blood pressure measurement and urinalysis.
