Using Biomarkers to Determine the Success of Ureteropelvic Junction Obstruction Surgery

Christina Ching, MD

Christina Ching, MD, pediatric urologist and physician-scientist at Nationwide Children’s Hospital

Biomarkers initially found to differ among patients with ureteropelvic junction obstruction and healthy controls may also objectively gauge post-surgical resolution of obstruction.

US News Badge UrologyUS News Badge Honor RollA follow-up study of a trial that initially identified four biomarkers that differ between healthy controls and pediatric patients about to undergo surgery for ureteropelvic junction obstruction (UPJO) has confirmed that two of these biomarkers may also be useful in determining whether the obstruction has successfully resolved post-surgery.

The study, published in the Journal of Pediatric Urology, found that levels of beta defensin 1 (BD-1) and hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP) — both of which were significantly elevated pre-surgery compared to healthy control patients — significantly decreased after successful UPJO surgery, with BD-1 returning to normal, healthy control levels.

“Diagnosis of obstruction currently relies exclusively on the use of radiologic studies, which can take their toll on families because they’re often invasive and time-consuming, and they can be ambiguous in many cases of UPJO,” says Brian Becknell, MD, PhD, a pediatric nephrologist and principal investigator in the Center for Clinical and Translational Research at Nationwide Children’s Hospital. “It would be nice to have urine biomarkers we could serially monitor and measure noninvasively over time to determine which patients might need surgery and which can be monitored on a conservative, nonoperative basis.”

 

The clinician-scientists behind the research examined follow-up urine samples at least 6 months after surgery (to allow time for complete surgery-related healing) for 13 of the original study’s 30 patients. All had successful resolution of their obstruction after surgery, as demonstrated via improved radiologic imaging and symptom resolution.

Their work is the first to demonstrate that HIP/PAP and BD-1 may offer clinicians not only a noninvasive and non-imaging-based method of detecting ureteral obstruction but also of monitoring its resolution post-surgery.

“We now need to show how these biomarkers behave in a larger group of patients,” says Christina Ching, MD, senior author of the study, pediatric urologist and a physician-scientist at Nationwide Children’s. “In addition, while this study was the first step in demonstrating the potential of these markers in evaluating for resolution of obstruction, it was actually a drawback of this study that all patients had a successful outcome from surgery. We need to follow some patients who do not respond to surgery to determine if biomarkers follow a different trajectory in that situation.”

To learn more about a wide range of obstruction-related biomarkers, the team will use a recently awarded R01 grant (Brian Becknell, MD, PhD, lead investigator) to prospectively follow about 300 young children with UPJO, with the hope of correlating serial urine findings with radiologic imaging and kidney function testing as needed.

REFERENCES:
Gupta S, Jackson AR, DaJusta DG, McLeod DJ, Alpert SA, Jayanthi VR, McHugh K, Schwaderer AR, Becknell B, Ching CB. Urinary antimicrobial peptides: Potential novel biomarkers of obstructive uropathy. Journal of Pediatric Urology. 2018 Jun;14(3):238.e1-238.e6. Gupta S, Nicassio L, Junquera GY, Jackson AR, Fuchs M, McLeod D, Alpert S, Jayanthi VR, DaJusta D, McHugh KM, Becknell B, Ching CB. Impact of successful pediatric ureteropelvic junction obstruction surgery on urinary HIP/PAP and BD-1 levels. Journal of Pediatric Urology. 2020 Mar;S1477-5131(20)30059-0. [Epub ahead of print].

A Decade of Remarkable Transformation: Urology

For the past decade, the Department of Urology has consistently led peers in collaborative innovation efforts such as PUMA, UTIGA and NURAG. The team has also been part of surgical firsts, including the first team to integrate clinical and surgical specialties for conditions requiring advanced colorectal and pelvic reconstruction interventions.

  • 2010: Nephrology-Urology Research Affinity Group (NURAG) Expands, Leading to More Than 100 Collaborative Publications Since Inception
  • 2012: Rama Jayanthi, MD, Appointed Chief of Urology
  • 2013: Center For Colorectal & Pelvic Reconstruction is World’s First to Formally Integrate Clinical and Surgical Specialties
  • 2016: Partnership with Dayton Children’s Enhances Regional Pediatric Urology Care
  • 2017: Nationwide Children's Joins Four Other Premier Children’s Hospitals to Form Pediatric Urology Midwest Alliance (PUMA)
  • 2020: Nationwide Children’s Urologists and Researchers Create the Urinary Tract Infection Global Alliance (UTIGA) — A Professional Society Focused on Solving Challenges Related to UTI management