Journal Spotlight: The RIVUR Study, Are Daily Antibiotics Necessary for Patients with Urinary Reflux?

Vesicoureteral reflux (VUR), or simply "reflux," is a congenital condition in which urine flows from the bladder back up towards the kidneys. An estimated 17% of children are born with or develop VUR. Reflux is present up to 30% of children with febrile urinary tract infections (UTI).[1] Urinary reflux predisposes these children to kidney infection, or pyelonephritis, which can be a serious infection requiring hospitalization. In very young babies, a single episode of pyelonephritis can lead to kidney damage and scar formation. Because of this risk, many pediatric urologists prescribe low dose, daily antibiotics to children with VUR, in an effort to prevent episodes of kidney infections. However, the benefit of prophylactic antibiotics remains controversial.

 
Hoberman, A., Greenfield, S., Matoo, K. et al.: Antimicrobial Prophylaxis for Children with Vesicoureteral Reflux. NEJM, 370: 2367, 2014


 
Recently, results from the RIVUR study (Randomized Intervention for Children with Vesicoureteral Reflux) were published and shed some light on the effects of using daily antibiotic prophylaxis in children with VUR.[above, 2] The RIVUR study was an ambitious effort by many physicians at 19 hospitals across the U.S. – Johns Hopkins was one of the leading sites. Over 600 children diagnosed with VUR were randomized to either once daily antibiotic (Bactrim, otherwise known as sulfamethoxazole and trimethoprim, TMP-SMX) versus placebo. They were followed closely with regular check-ups over the next 2 years.
    
The RIVUR study demonstrated two key things: First, children given prophylaxis had 50% fewer febrile infections over time when compared to children not taking antibiotics. 

In the RIVUR Study, fewer children assigned to TMP-SMX prophylaxis had a UTI than children assigned to placebo (P<0.001 by log-rank test).  As presented in the New England Journal of Medicine (2014;370:2367-2376).

However, children given antibiotics did not show less kidney scarring compared to the children not given antibiotics. This may mean that the antibiotics did not prevent scarring, OR it may mean that the kidney scarring was too small to see based on our current imaging techniques. Parents, pediatricians, and pediatric urologists may interpret the results of the RIVUR study as a reason to stop the use of antibiotics in children with VUR. In our own practice, at Johns Hopkins Children's Center, we continue to emphasize the importance of incorporating science and tailoring the treatment plan based on each child/family.

Overall, the benefits of daily antibiotics on preventing kidney damage remain controversial and the use of daily antibiotics should be balanced with patient factors, frequency of febrile UTIs and family dynamics.

Jason Michaud, MD, PhD

Ming Hsien Wang, MD

This blog was written by Jason Michaud, MD, PhD, PGY4 urology resident, and Ming-Hsien Wang, MD, Assistant Professor of Urology and Director of the Pediatric Urology Fellowship Program at the Brady Urological Institute and Johns Hopkins Children's Center.

 





References
1. Sargent, MA. What is the normal prevalence of vesicoureteral reflux? Pediatr. Radiol. Sep;30(9):587-93, 2000.
2. Hoberman, A., Greenfield, S., Matoo, K. et al.: Antimicrobial Prophylaxis for Children with Vesicoureteral Reflux. NEJM, 370: 2367, 2014