Vesicoureteral reflux (VUR) is classified as primary or secondary, and this guideline only describes the management of VUR secondary to neurogenic bladder. The goal of treatment, as with neurogenic bladder, is to first protect the patient’s renal function. Before secondary VUR can be corrected, the predisposing factors for VUR, such as DSD, hypocompliant bladder, pathologic intravesical hypertension, and urinary tract infection, must first be corrected. Some of the secondary VUR can be reduced or even disappear with the correction of DSD and improvement of bladder compliance. Minimally invasive or open surgical treatment can be considered for VUR that persists after correction of the predisposing factors.
1. Diagnosis
Imaging is the basis for the diagnosis and treatment of VUR. Common methods include urological ultrasound, cystourethrography, and renal nuclear scan. History taking and recording of voiding diary, urinary flow rate, and residual urine volume measurement are important to understand whether there is dysfunction in the lower urinary tract. Urinary tract infection is one of the causative factors of VUR and further management is mandatory when urinary tract infection is present in patients with neurogenic bladder. Routine imaging urodynamics is highly recommended to confirm the diagnosis of reflux, determine the degree of reflux, and to understand the type of bladder dysfunction and bladder pressure during reflux.
The International Reflux Society has graded the degree of VUR, which provides criteria for the treatment and evaluation of the efficacy of reflux, and this guideline also recommends this grading method:
Grade 1: Reflux not reaching the renal pelvis, with varying degrees of ureteral dilatation;
Grade 2: Reflux to the renal pelvis without dilatation of the collecting system and a normal renal vault;
Grade 3: Mild or moderate ureteral dilatation with or without ureteral tortuosity, with mild dilatation of the collecting system;
Grade 4: Moderately dilated ureter with or without tortuosity and blunted renal vault, but the renal papillae are still visible on the image;
Grade 5: Dilated and tortuous ureter is clearly visible, the collecting system is clearly dilated, the renal papillae are absent, and the renal parenchyma is visible.
The radiation exposure of children with reflux during radionuclide examination is less than that of cystourethrography, but the images are poorer. Recent studies have shown better diagnostic results with voiding sonography and magnetic resonance urography, but given the cystourethral morphology and reflux grading criteria, x-ray cystourethrography remains the “gold standard” for the evaluation of VUR.
Urological ultrasound is usually performed at one week of life. The presence of VUR can be confirmed by observing the degree of dilatation of the collecting system in the filled and empty bladder. The thickening and morphology of the bladder wall may indirectly reflect the presence or absence of lower urinary tract symptoms and reflux. The absence of hydronephrosis at birth may exclude severe urinary tract obstruction, but not VUR. cystourethrography reveals reflux, and further DMSA nuclear imaging may be performed to assess the extent of renal damage.
2.Treatment
When VUR does not disappear after successful control of urinary tract infection, filling phase and voiding bladder hypertension, anti-reflux surgical treatment is required.
(1) Conservative treatment.
For mild reflux without renal damage, conservative treatment can be used, including observation and follow-up, intermittent or continuous antibiotic prophylaxis application, and voiding training. Foreign scholars have suggested circumcision in children as part of conservative treatment, thus reducing the incidence of urinary tract infections in some children. Once symptomatic urinary tract infections such as fever occur, termination of conservative treatment and further other therapeutic measures should be considered.
(2) Surgical treatment.
Surgical treatment includes endoscopic ureteral orifice filler injection anti-reflux surgery and ureteral bladder reimplantation anti-reflux surgery.
(1) Filler injection anti-reflux surgery: Filler injection anti-reflux surgery refers to the use of cystoscopy to inject a certain volume of filler under the mucosa in the distribution of the population of the ureteral orifice or ureter into the bladder, to achieve the purpose of treating VUR by lengthening the inner segment of the ureteral bladder wall or elevating the ureteral orifice and narrowing the lumen, and the ureteral orifice forms a crater-like appearance after injection. Fillers injected include polytetrafluoroethylene (PTFE, or Teflon), collagen, autologous fat, polydimethylsiloxane, silicone, chondrocytes, and polyglycolic/hyaluronic acid fluid (Deflux). PTEE has been effective in adult anti-reflux applications, but has not been allowed in children. Collagen and chondrocyte treatment are less effective, and Deflux is currently more widely used abroad but not much used in China.
The advantage of this method is that the damage is less than that of open surgery, and the recent success rate after injection is 65%-75%, so it is recommended. After the injection, ultrasound and cystourethrography during the voiding period can be repeated 6 months after the first injection if reflux still exists. Repeat injections are not effective and open surgery may be considered. Previously receiving filler injections for anti-reflux does not make open surgery more difficult.
②Ureteral bladder anti-reflux reimplantation:The basic principle of ureteral bladder anti-reflux reimplantation is to implant the ureter subliminally from the submucosa of the bladder to extend the length of the ureter in the bladder lining. The success rate of the procedure is as high as 92% to 98%.
Ureteral bladder anti-reflux reimplantation can be divided into three major categories: extra-vesical, intra-vesical and combined intra- and extra-vesical operations. Currently, the commonly used procedures are Cohen’s procedure, Politano-Leadbetter’s procedure, Paquin’s procedure, Glenn-Anderson’s procedure, etc. The ureter should be cut or folded to reduce the caliber of the ureter if it is thick. The most commonly used and reliable procedure is Cohen-type vesicoureteral reimplantation. In recent years, minimally invasive laparoscopic surgery for ureteral reimplantation has achieved the same results as open surgery; however, the disadvantage of laparoscopic subsurgery is that it is time-consuming, and its advantages over open surgery are still controversial, and it is not yet the recommended surgical procedure.
The most common postoperative complication is the failure to eliminate the VUR; the next most common complication is postoperative obstruction of the ureteral bladder junction, which may be due to scarring due to disruption of the ureteral blood supply, or distortion of the ureteral penetration into the bladder wall segment; there are also cases of postoperative reflux and obstruction together. Ultrasound review can be performed 4 to 8 weeks after surgery to rule out postoperative obstruction, and a voiding cystourethrogram can be performed 2 to 4 months after surgery to determine the success of the procedure, followed by regular follow-up with reference to the principles of neurogenic bladder.
Patients with hypocompliant bladder often require bladder enlargement, and it remains controversial whether ureteral bladder reimplantation should be performed at the same time when there is vesicoureteral reflux. The literature has shown satisfactory long-term results for high grade VURs such as grade IV-V and grade III-V with simultaneous ureteral anti-reflux reimplantation during bladder enlargement, and it is believed that in such severe reflux, ureteral reimplantation should be performed at the same time as bladder enlargement, otherwise residual reflux and retrograde infection are likely. However, it has also been suggested that most ureteral reflux (especially reflux below grade IV or high-pressure reflux) can resolve on its own after bladder pressure is reduced by bladder enlargement alone, and the percentage of reflux cured is not related to the severity of reflux. Therefore, this guideline recommends that ureteral anti-reflux reimplantation should be performed in conjunction with bladder enlargement for severe VUR (high-grade and/or low-pressure reflux), and does not recommend ureteral anti-reflux reimplantation alone without bladder enlargement.
3. Prevention and follow-up
Regular imaging follow-up including renal ultrasound, cystourethrography, nuclear scans and DMSA scans should be considered as part of conservative treatment to regularly monitor the progression of VUR, self-healing and the patient’s renal functional status. The frequency of follow-up varies from person to person and should include at least two ultrasound examinations and one imaging urodynamic examination per year, and further investigations (e.g. cystoscopy and DMSA scan) should be performed if disease progression is detected.