eMedicine Specialties > Pediatrics: Surgery > Urology

Vesicoureteral Reflux: Treatment & Medication

Author: Caleb P Nelson, MD, MPH, Instructor in Surgery, Department of Urology, Harvard Medical School; Consulting Staff, Division of Pediatric Urology, Department of Urology, Children's Hospital Boston
Coauthor(s): Harry P Koo, MD, Chairman of Urology Division and Director of Pediatric Urology, Virginia Commonwealth University; Professor of Surgery, VCU School of Medicine, Medical College of Virginia; Director of Urology, Children's Hospital of Richmond
Contributor Information and Disclosures

Updated: Sep 9, 2008

Treatment

Medical Care

The treatment of children with reflux aims to prevent kidney infection, kidney damage, and the complications of kidney damage. Treatment options include surveillance, medical therapy, and surgical therapy. Walker summarized the following general principles of management in children with known vesicoureteral reflux (VUR): (1) spontaneous resolution of vesicoureteral reflux is common in young children but is less common as puberty approaches, (2) severe reflux is unlikely to spontaneously resolve, (3) sterile reflux, in general, does not result in reflux nephropathy, (4) long-term antibiotic prophylaxis in children is safe, and (5) surgery to correct vesicoureteral reflux is highly successful in experienced hands.³

• Surveillance is infrequently used for numerous reasons. Although no large randomized trials have been conducted establishing the efficacy of prophylactic antibiotics in prevention of either urinary tract infection (UTI) or renal scarring, several decades of clinical practice have demonstrated that antibiotic prophylaxis is usually well-tolerated, and clinicians are reluctant not to offer some treatment. Medicolegal concerns regarding the risk of kidney damage while on surveillance have likewise limited the use of this approach. Surveillance is still frequently used among older children with vesicoureteral reflux, especially boys who have never had a UTI.
• Initial treatment of the child with a UTI involves supportive care and prompt administration of appropriate antibiotics.
  • Timely institution of antibiotic therapy has been shown to be critical in preventing scar formation in kidneys with pyelonephritis.
  • Animal studies have demonstrated that permanent renal damage occurs if antibiotics are not started within 72 hours, although other studies indicate an even shorter window of opportunity. For this reason, clinicians must maintain a high index of suspicion for UTI in children.
  • Medical treatment with prophylactic antibiotics remains the mainstay of initial management of vesicoureteral reflux (see Medication). Because vesicoureteral reflux spontaneously resolves in most children, medical management allows this natural history to take its course while providing some measure of protection against recurrent UTI and renal injury.
  • Prophylaxis should be started once a child has completed treatment of the initial UTI (see Medication) and continues at least until imaging reveals vesicoureteral reflux. If no vesicoureteral is seen, prophylaxis is discontinued. If vesicoureteral reflux is present, prophylactic antibiotics are continued until (1) vesicoureteral reflux resolves, (2) vesicoureteral reflux is surgically corrected, or (3) the child grows old enough that prophylaxis is deemed no longer necessary.
• Virtually all children with a new diagnosis of grade I-IV reflux, and some with grade V, are given a trial of medical treatment. This consists of antibiotics dosed at one fourth of the therapeutic dosage and regular follow-up care and imaging. A typical routine includes renal ultrasonography and VCUG or nuclear cystography every 12-18 months.
  • Since a substantial number of children experience spontaneous resolution of vesicoureteral reflux (50-85% of cases with grade I-III), medical treatment spares this group the morbidity of surgery while protecting the kidneys from further damage.
  • Once follow-up imaging demonstrates resolution of vesicoureteral reflux, antibiotics are discontinued. The importance of conscientious follow-up care during medical management cannot be overemphasized. Lack of compliance with medications or surveillance imaging may result in progression of reflux nephropathy and renal failure in children who are susceptible.
• In boys with persistent vesicoureteral reflux who have not had recurrent UTIs, antibiotics are often discontinued as the boys approach puberty. However, because of concerns about future pregnancies, surgery may be recommended in girls approaching puberty who have persistent vesicoureteral reflux (see Follow-up).
• In recent years, the role of prophylaxis with antibiotics has been challenged.
  • Several studies have failed to find any decrease in the incidence of UTIs in children with vesicoureteral reflux who take antibiotics. However, all of these studies have significant flaws that make it difficult to state with certainty that antibiotics prophylaxis is ineffective. Furthermore, decades of clinical experience has suggested that, in many children, antibiotic prophylaxis is a key component of management.
  • Ongoing studies, including a large randomized trial of antibiotic prophylaxis in children with vesicoureteral reflux funded by the National Institute of Health, will hopefully shed more light on the proper role of antibiotics.
  • However, note that these uncertainties apply only to the role of antibiotics in prevention. The role of antibiotics in the treatment of acute UTI is not debatable, and failure to institute appropriate therapeutic antibiotics in the setting of pyelonephritis (kidney infection) is associated with permanent renal injury and scarring. Children at risk for such infection, such as those with vesicoureteral reflux, need prompt and timely evaluation of possible UTI to prevent such outcomes.
• Bladder and bowel management for dysfunctional elimination is as follows:
  • Anticholinergic medication, in conjunction with timed voiding, may improve symptoms of dysfunctional voiding and reduces the risk of infection. Anticholinergic agents should be used in select patients so as not to compound the problems of incomplete bladder emptying or worsening constipation.
  • A few of these patients benefit from some form of bladder training to achieve balanced, low-pressure voiding with coordinated relaxation of the external sphincter and pelvic floor. In children with primary bowel elimination problem, treatment with enemas, dietary changes, and stool bulking agents, in coordination with a pediatric gastroenterologist, is critical for success.

Surgical Care

• Open antireflux surgery
  • The decision to proceed to antireflux surgery is based on many factors, and the medical, social, and emotional needs of the patient and the family must be considered. Accepted indications for surgical treatment include the following: (1) breakthrough febrile UTIs despite adequate antibiotic prophylaxis; (2) severe reflux (grade V or bilateral grade IV) that is unlikely to spontaneously resolve, especially if renal scarring is present; (3) mild or moderate reflux in females that persists as the patient approaches puberty, despite several years of observation; (4) poor compliance with medications or surveillance programs; and (5) poor renal growth or function or appearance of new scars.
  • Virtually all open antireflux operations involve reconstruction of the ureterovesical junction (UVJ) to create a lengthened submucosal tunnel for the ureter, which functions as a one-way valve as the bladder fills. Dozens of procedures have been described. Surgery for vesicoureteral reflux should be performed by a qualified pediatric urologist, experienced in multiple techniques, allowing tailoring of the surgery to the unique anatomic circumstances of the individual patient.
  • Although several studies have shown that antireflux surgery decreases the incidence of pyelonephritis, randomized trials of antibiotic prophylaxis versus surgical therapy plus antibiotic prophylaxis have not shown a difference in development of nonfebrile UTI, renal scarring, or renal failure. However, most of these studies were statistically underpowered, and the true benefit of antireflux surgery is still incompletely understood.
• Intravesical approach
  • The bladder is opened anteriorly via a low abdominal incision. The ureters are separated from their attachments to the bladder muscle and connective tissue and repositioned under a submucosal tunnel to create the necessary 5:1 length-to-diameter ratio.
  • Developed in the 1950s, the prototypical intravesical operation is the Politano-Leadbetter procedure. The ureter is dissected completely free of its attachments and passed through a new muscular hiatus created higher on the bladder wall. The ureter is then passed down through a submucosal tunnel, and the orifice is sutured to the mucosa at its original meatal position. This procedure has a reported success rate of 97-99%.
  • An evolution of the Politano-Leadbetter procedure is the Cohen cross-trigonal technique, which is probably the most popular intravesical repair performed today. In this repair, the original muscular hiatus is used, but the ureter is dissected from its attachments and pulled across the trigone through a submucosal tunnel, and the meatus is sutured into a new position at the end of the tunnel. Reported rates of success range from 97-99% with this technique as well.
• Extravesical approach
  • This was developed in an effort to avoid the time and morbidity associated with the cystotomy and ureteral anastomosis required for intravesical repair. It is particularly useful in patients with unilateral reflux.
  • Developed concurrently in Europe and the United States, the Lich-Gregoire repair approaches the bladder via the retroperitoneum. The ureter is dissected from the detrusor, but the orifice is left intact. A narrow furrow in the detrusor then is created, down to but not disrupting the mucosa, extending cephalad from the ureteral orifice. The distal ureter is then laid into this furrow and the detrusor closed over it. Although early American results were disappointing, further experience and modifications have demonstrated success rates comparable to the standard intravesical techniques.
  • One complication of the extravesical approach is postoperative urinary retention, which generally resolves spontaneously. Judicious use of bipolar electrocautery during the posterior bladder dissection can reduce incidence of this complication to less than 5%. Rare reports of permanent voiding dysfunction and retention in patients undergoing bilateral extravesical procedures have led some surgeons to use this technique only for unilateral cases.
• Endoscopic antireflux surgery
  • The most dramatic change in the treatment of vesicoureteral reflux over the past decade has been the rapid growth in the use of endoscopic treatment. Although these techniques have been used in Europe for many years, only since the introduction (and approval by the US Food and Drug Administration [FDA] in 2001) of injectable dextranomer/hyaluronic acid copolymer (DHA) has endoscopic treatment become widespread in the United States. The perceived benefits of endoscopic treatments include short surgical time, low surgical morbidity, comparable success rates, and preservation of the option for subsequent open surgical repair.
  • Some clinicians are now advocating endoscopic treatment as initial management for newly diagnosed vesicoureteral reflux. They argue that immediate antireflux surgery obviates the need for long-term antibiotics and repeated imaging studies. However, such a strategy inevitably results in the overtreatment of a large number of children because vesicoureteral reflux spontaneously resolves in most children, and even those with persistent vesicoureteral reflux may not have a clinical indication for antireflux surgery. Finally, the true long-term success rates for endoscopic treatment with DHA are still to be determined.
  • Endoscopic techniques involve injection of a bulking substance into the muscular posterior wall of the UVJ. The resulting bulking effect compresses the ureteral lumen and provides a substitute for the normal muscular backing of the transmural ureter.
  • Some authors emphasize the importance of creating a large mound or "volcanic" appearance of the bulking agent under the orifice, compressing the orifice into a slit. Other authors have described an intramural injection, in which the distal ureter is distended with a jet of saline from the cystoscope, allowing the injection needle to be advanced into the submucosa of the intramural ureter at 6 o'clock.
  • In general, success (resolution of vesicoureteral reflux on postprocedure imaging) rates with endoscopic treatment are significantly lower than those reported for open antireflux surgery. A meta-analysis of over 5000 patients undergoing endoscopic treatment with various bulking agents found a success rate of 74% after one injection and 85% after one or more injections.⁶ The success rate in this meta-analysis among the DHA studies was 69% after one injection.
  • Most studies of endoscopic treatment have found that success rates are lower for higher grades of vesicoureteral reflux (the very patients most likely to need antireflux surgery). The meta-analysis found a success rate of 63% after one injection for grade IV vesicoureteral reflux.
  • Single center reports have noted significantly higher success rates with DHA, with resolution rates of over 90% with one or more injections at some centers.
  • Other bulking agents have been used extensively in Europe, in particular, polytetrafluoroethylene (Teflon). Although thousands of patients have undergone treatment with Teflon over the past 30 years, persistent concerns over the safety of this bulking agent have limited its use in the United States.
  • Other bulking agents that have been reported include autologous fat, blood, and chondrocytes; bovine collagen; and polydimethylsiloxane. Although all have certain advantages, concerns over particle migration, carcinogenesis, and technical handling problems have limited their use.
  • Children who undergo endoscopic antireflux surgery need continued follow-up. They require postprocedure imaging, including voiding cystourethrography (VCUG) at 3-4 months postsurgery. Patients should be maintained on antibiotic prophylaxis until resolution of vesicoureteral reflux is confirmed.
  • Recent studies of endoscopic surgery with DHA have found that as many as 25% of children whose vesicoureteral reflux was cured on the initial VCUG (3-4 mo) VCUG subsequently had recurrence of vesicoureteral reflux on delayed VCUG (12 mo). The reasons for late failure of endoscopic therapy are uncertain, but may include reabsorption of the injected material, migration of the injected material, or secondary patient factors such as dysfunctional voiding. Some clinicians are now recommending additional VCUG at 12-18 months postsurgery because of concerns over the durability of DHA implant. 
  • Delayed adverse effects of DHA antireflux surgery appear to be uncommon. However, recent studies have observed that the DHA implants can strongly resemble a kidney stone in the distal ureter on CT scanning, apparently due to calcification of the DHA implant. Because many children who undergo DHA injection for treatment of vesicoureteral eventually undergo CT scan for numerous reasons, treating physicians and radiologists must recognize that DHA implants may produce a misleading appearance on CT scanning.

Consultations

• Good communication between the urologist and primary care physician is essential for the effective management of vesicoureteral reflux. This is especially true for children being treated medically, in whom regular follow-up care and prompt evaluation and treatment of breakthrough UTI are critical in preventing renal damage.
• Involvement of a pediatric nephrologist is indicated for children at risk of or manifesting evidence of reflux nephropathy.

Diet

• Children with frequent UTIs often have concurrent problems with constipation and poor bowel habits. Institution of a bowel program in these children can reduce the frequency of infection.
• High-fiber diets combined with a stool softener, such as docusate (Colace), can improve bowel function and reduce colonic and rectal dilation.
• For severe cases, daily polyethylene glycol (Miralax) is often used.

Activity

• Children with vesicoureteral reflux can engage in normal activity.
• Toilet hygiene, especially proper wiping technique in girls, should be taught to children of appropriate age to reduce the frequency of UTI.

Medication

Antibiotics

These are used for maintenance of sterile urine. Antibiotic agents used for prophylaxis in children with vesicoureteral reflux (VUR) are chosen for their efficacy in the urinary tract, safety, and tolerability. The typical dose is one fourth of the therapeutic dose. They are usually administered as suspensions once daily, typically in the evening to maximize overnight drug levels in the bladder. In neonates with antenatally diagnosed hydronephrosis and in infants younger than 8 weeks who have been treated for urinary tract infection (UTI), the agent of choice is amoxicillin. For older children, the most common antibiotics used are trimethoprim-sulfamethoxazole, nitrofurantoin, and penicillins. The cephalosporins are used less often.

Amoxicillin (Amoxil, Biomox, Trimox)

Interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria. Is generally well tolerated, although has a higher rate of fecal resistance than some other agents. Metabolized effectively by newborns, making it a good choice for neonates.

Sulfamethoxazole and trimethoprim (Bactrim, Septra, Cotrim)

Inhibit bacterial growth by inhibiting synthesis of dihydrofolic acid. DOC in children >6-8 wk. The maturing hepatobiliary system is able to process trimethoprim-sulfamethoxazole combination agents, which have an excellent urinary concentration profile and tend to cause fewer fecal resistance problems. Well tolerated orally.

Nitrofurantoin (Furadantin, Macrodantin)

Synthetic nitrofuran that interferes with bacterial carbohydrate metabolism by inhibiting acetylcoenzyme A. Bacteriostatic at low concentrations (5-10 mcg/mL) and bactericidal at higher concentrations.
Another common urinary antiseptic agent for children >8 wk. Unpleasant taste of the liquid form makes it unacceptable to some children. Older children who can tolerate tablets do well with this medication.

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