Point-of-Care Urinary Biomarker Predicts Poor Outcomes in Combat Casualties

By Will Boggs MD

August 13, 2019

NEW YORK (Reuters Health) - A point-of-care dipstick test for urine neutrophil gelatinase-associated lipocalin (NGAL) is useful for risk prediction in critically injured soldiers, researchers report.

"While urinary biomarkers have long been a promised breakthrough, to date they have not obtained widespread clinical use," said Dr. Ian J. Stewart from David Grant USAF Medical Center, Travis Air Force Base, in California, and Uniformed Services University of the Health Sciences, in Bethesda, Maryland.

"However, the evidence for their clinical use is accumulating," he told Reuters Health by email.

Previous studies have suggested that urinary biomarkers can provide useful prognostic information in combat casualties, but their feasibility and utility in the setting of a combat zone remain unclear.

Dr. Stewart and colleagues evaluated two point-of-care urinary biomarker tests: NephroCheck, which assesses the levels of tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7), and NGALds, which assesses the levels of NGAL. Their study included 89 patients with combat casualties admitted to the ICU at Craig Joint Theater Hospital in Bagram Airfield, Afghanistan.

Six patients (6.7%) required renal-replacement therapy (RRT), and nine died (10.1%), with 12 patients (13.5%) experiencing the combined outcome of RRT or death, the researchers report in the Journal of the American College of Surgeons, online July 19.

Among patients with a NephroCheck test score below the 0.3 cutoff, 9% developed the combined outcome, compared with 26% of those with a higher score.

One percent of patients with a "low risk" NGALds score (<50 ng/mL) developed the combined outcome versus 7% of those with a "high risk" score (>300 ng/mL).

As a continuous variable, the NephroCheck test score was not significantly associated with the combined outcome. In contrast, when considered as a continuous variable, the NGALds test was highly associated with the combined outcome, even after adjustment for the injury-severity score.

At the point of optimal performance (moderate risk or higher) the NGALds test had 75% sensitivity, 82% specificity, 39% positive predictive value and 95% negative predictive value for the combined outcome. Its overall accuracy (by AUC) was 84%.

"NGALds, especially if it can be combined with other markers, can allow for the specific quantification of risk," Dr. Stewart said. "In the long-term, I believe that biomarkers (like NGAL) will play a vital role in patient selection for pivotal clinical trials."

"Key to designing effective trials is to identify patients that will be the most likely to benefit from the intervention," he said. "Biomarkers like NGAL will allow us to do this."

Dr. Stewart added, "I would like to take this opportunity to thank the service members that participated in this study. Caring for these brave, young men and women has been the honor of my professional career."

The study had no commercial funding, and the authors declared no conflicts of interest.

SOURCE: https://bit.ly/3312Me4

J Am Coll Surg 2019.