(From the June 2016 Issue of Research Now)
Urinary tract infections (UTIs), caused by bacteria, are one of the most common infections in children and account for millions of unplanned pediatrician and urgent care visits each year in the United States. Previous research has shown that antimicrobial peptides, referred to as AMPs, are found in the urine and kill bacteria, and that the abundance of these peptides rises significantly in adult patients with UTIs. In a novel study on pediatric patients, a multi-institutional team including clinician-scientists from Nationwide Children’s Hospital also found AMPs to be effective biomarkers for aiding in diagnosis of UTIs in children.
“Long-standing methods used to clinically identify UTIs have several shortcomings,” says Andrew Schwaderer, MD, research director in the Section of Nephrology at Nationwide Children’s Hospital and senior author of the study, which was recently published in the journal Pediatric Research. “Urinalysis, specifically, has limited accuracy and urine culture takes 24 hours to complete.”
For these reasons, the team was looking for diagnostics that would allow for more accurate and rapid treatment of UTIs in children. After completing a preliminary study of adult emergency department patients, researchers found that some AMPs were good markers for diagnosing infection.
Since the body’s immune system differs with age, the team then conducted a study of children in the Emergency Department and Urgent Care to determine if findings would be applicable for a pediatric patient population.
“We collected urine samples from children at Nationwide Children’s Hospital that had urinalysis and urine cultures ordered for clinical indications,” says Dr. Schwaderer, who is also a principal investigator in the Center for Clinical and Translational Research at The Research Institute at Nationwide Children’s. “We measured urine antimicrobial peptide levels and normalized these levels to urine creatinine to control for differences in urine concentration between patients.”
Specifically, human alpha defensin 1 and human alpha defensin 5 were the two antimicrobial peptides measured in the urine. Researchers compared the levels of these antimicrobial peptides to the urine culture and urinalysis, including comparison to leukocyte esterase, an enzyme produced by white blood cells.
A leukocyte esterase test (LE test) is a urine test that screens for the presence of white blood cells in urine, which usually indicates a urinary tract infection. The team examined whether tests involving the AMPs, either individually or in combination with LE, were better at detecting infection, with a focus on both the specificity and the sensitivity of the test.
“The combination test of LE and human alpha defensin 5 had increased specificity without decreasing sensitivity, when compared to the test results on urinalysis when LE levels were the same as or greater than trace amounts,” explains Joshua Watson, MD, attending physician in Infectious Diseases at Nationwide Children's and co-author of the study. “Specificity refers to the ability of the test to identify samples that are truly negative, while sensitivity refers to the ability of the test to identify samples that are truly positive.”
Since preliminary findings have shown that AMPs are good biomarkers in adults and children, researchers now hope to develop what is known as a lateral flow assay, according to Dr. Schwaderer. The test would be similar to current, fast-acting pregnancy tests, providing answers within a matter of minutes for the hundreds of thousands of children and adults annually impacted by UTIs.
“In the future, we plan to develop and prospectively study this rapid, point-of-care test for alpha defensin 5 levels in urine, to see if this test can result in more accurate and rapid diagnosis of urinary tract infections,” says Dr. Schwaderer.
Caterino JM, Hains DS, Camargo CA, Quraishi SA, Saxena V, Schwaderer AL. A prospective, observational pilot study of the use of urinary antimicrobial peptides in diagnosing emergency department patients with positive urine cultures. Academic Emergency Medicine. 2015 Oct;22(10):1226-30.
Watson JR, Hains DS, Cohen DM, Spencer JD, Kline JM, Yin H, Schwaderer AL. Evaluation of novel urinary tract infection biomarkers in children. Pediatric Research. 2016 Feb 17 [Epub ahead of print].