Researchers Identify Predictors of Recurrent UTIs

Urinary tract infections (UTIs) are common bacterial infections that are not only aggravating for youngsters and their parents, but they also can have serious long-term consequences. That is why it is valuable for clinicians to be able to better predict which children are most susceptible to repeated UTIs.

Instigated by a buildup of bacteria in the urine, UTIs cause uncomfortable burning with urination, abdominal pain, and frequent urination or wetting accidents. If the bacterial infection reaches the kidneys, symptoms also may include a fever, lack of appetite, and irritability. Most UTIs do not lead to complications with proper treatment, but permanent scarring of the kidneys may occur in severe cases. The Children’s Hospital of Philadelphia treats more than 800 patients with UTIs each year.

Ron Keren, MD, MPH, of Clinical Futures, a CHOP Research Institute Center of Emphasis, and an attending physician at CHOP, and colleagues conducted a research study that aimed to identify the risk factors that may contribute to why some children go on to develop another UTI. The results showed that two of the strongest risk factors are vesicoureteral reflux (VUR) and bowel and bladder dysfunction (BBD). These findings reported in the journal Pediatrics may have important implications for clinical practice. “

We think that about 5 percent of kids in the first five, six years of life are going to have a urinary tract infection,” Dr. Keren said. “The focus of clinicians and researchers for the last few decades regarding children who have had UTIs has been on VUR, but there has been very little attention paid to children who don’t have VUR.”

VUR is a condition during urination when the bladder contracts and some of the urine flows up the ureters back toward the kidneys where the urine came from. VUR allows bacteria that may be in the bladder to travel with the refluxing urine to the kidney.

Bladder dysfunction often occurs when a child gets into a habit of holding in urine for long periods, which stretches the bladder so much that it does not empty completely. Bacteria have the chance to multiply in residual urine left over in the bladder after incomplete voiding.

In a previous study, called the Randomized Intervention for Vesicoureteral Reflux (RIVUR) study, children with VUR who had a UTI were randomized to receive daily prophylaxis with antibiotic or placebo. Dr. Keren and his colleagues also conducted a complementary study, called the Careful Urinary Tract Infection Evaluation (CUTIE), in which they compared 305 children from the RIVUR placebo group to another cohort of 195 children who had UTIs but did not have VUR. They observed the children in the two CUTIE groups for two years.

“For the first time, we could follow the natural history of what happens to kids who have had a first or second UTI and aren’t getting any therapy,” Dr. Keren said. “And we could see how much of a differentiator VUR is in terms of subsequent UTIs.”

The rate of recurrent UTIs in children who did have VUR was 25 percent; however, the highest risk of recurrent UTIs was for children who had a combination of any degree of VUR and BBD: 56 percent. If the child only had BBD, the rate was still high: 35 percent. The association between BBD and an increased risk of recurrent UTIs is noteworthy because BBD was a common problem among children enrolled in CUTIE: 59 percent (with VUR) and 46 percent (no VUR).

These observations support the researchers’ suspicions that BBD can be a key driver of UTIs. If future larger studies validate CUTIE’s findings, it may give clinicians evidence in order to tailor their treatment approaches and help families decide whether the benefits of daily prophylaxis outweigh the risks and inconvenience.

“The idea is to move toward a more individualized but data-driven approach to decide who should and shouldn’t get prophylaxis,” Dr. Keren said.

For example, urologists who run the DOVE Center for Voiding and Bladder Function at The Children’s Hospital of Philadelphia give prophylactic antibiotics to children who are undergoing bowel and bladder retraining to prevent UTI recurrences. The program uses behavior modification techniques to teach children to regain bowel and bladder control, and UTIs likely would sidetrack their success.

Three of the 19 clinical trial centers that collaborated on RIVUR study also enrolled patients in CUTIE: The Children’s Hospital of Philadelphia, The Children’s Hospital of Pittsburgh of UPMC, and Children’s National Medical Center, Washington, D.C. CUTIE was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases and the National Center for Advancing Translational Sciences.