What is grade 4 vesicoureteral reflux (VUR), its causes, and management options?

From the Guidelines

Grade 4 vesicoureteral reflux (VUR) is a severe condition that requires aggressive management, including continuous antibiotic prophylaxis (CAP) and surgical intervention, to prevent recurrent urinary tract infections (UTIs), renal scarring, hypertension, and potential kidney function impairment. The condition is characterized by significant dilation of the ureter, renal pelvis, and calyces due to an abnormal valve mechanism at the ureterovesical junction, which can be congenital or acquired. Management of grade 4 VUR involves both medical and surgical approaches. Medical management includes CAP with medications like trimethoprim-sulfamethoxazole (2-3 mg/kg once daily) or nitrofurantoin (1-2 mg/kg once daily) to prevent UTIs, as supported by recent guidelines 1. Surgical intervention is often necessary for grade 4 VUR and may include endoscopic injection of bulking agents at the ureterovesical junction, with a success rate of 63% for grade IV reflux 1, ureteral reimplantation surgery (ureteroneocystostomy), or in severe cases with kidney damage, partial nephrectomy. Some key points to consider in the management of grade 4 VUR include:

• Regular monitoring with voiding cystourethrography (VCUG) and renal ultrasounds to track reflux resolution and kidney growth
• Educating parents about recognizing UTI symptoms, maintaining good hygiene, ensuring regular bladder emptying, and increasing fluid intake
• Considering the risks and benefits of CAP, including the potential for antibiotic resistance and the need for individualized treatment plans 1
• Offering surgical correction to patients with frequent breakthrough infections or persistent high-grade reflux, as recommended by recent guidelines 1
• Selecting the most appropriate management option based on factors such as the presence of a focal uptake defect on a radionuclide scan, clinical course, grade of reflux, ipsilateral renal function, bilaterality, bladder function, associated anomalies of the urinary tract, age, sex, compliance, and parental preference 1.

From the Research

Definition and Causes of Grade 4 Vesicoureteral Reflux (VUR)

• Grade 4 VUR is a condition where urine flows backward from the bladder into the kidneys, causing increased risks of urinary tract infection, renal scarring, and reflux nephropathy 2.
• The causes of VUR are not fully understood, but factors such as high grade, bladder/bowel dysfunction, and voiding cystourethrography (VCUG) findings can increase the likelihood of persistence and renal scarring 2.

Management Options for Grade 4 VUR

• Observation is suitable only for patients at low risk of renal injury, while antibiotic prophylaxis can reduce the incidence of UTIs, but has drawbacks such as antibiotic resistance and incomplete adherence 2.
• Endoscopic injection, such as Deflux injection, has been shown to be an effective treatment for VUR, with a significant reduction in disease severity seen in patients with grade II to IV disease after a single injection 3.
• Ureteral reimplantation is still performed commonly, and robot-assisted laparoscopic methods are gaining popularity 2.
• Endoscopic treatment with stabilized non-animal hyaluronic acid/dextranomer gel (NASHA/Dx) has been associated with a low number of febrile UTIs following treatment, and is viewed positively by patients and parents 4.
• Sub-ureteric teflon injection (STING) has also been shown to be effective in correcting VUR, with a success rate of 86.6% and no complications reported 5.
• A study on endoscopic treatment of Grade 4-5 primary VUR in infancy and childhood found that 67% of patients were symptom-free and 84% did not require further intervention after one injection, and 98% after further injections 6.

Factors Influencing Success in Endoscopic Treatment of Grade 4 VUR

• Factors such as age under 1 year, female gender, postnatal versus antenatal presentation, duplex anatomy, circumcision status, and presence of congenital uptake defects on DMSA may influence the outcome of endoscopic treatment 6.
• However, a study found that males had a significantly better outcome than females, irrespective of circumcision status, and that duplex systems had a similar outcome to single systems 6.
• The presence of uptake defects on DMSA prior to intervention did not have any difference on outcome 6.