The potential utility of urinary biomarkers for risk prediction in combat casualties: a prospective observational cohort study

Abstract

IntroductionTraditional risk scoring prediction models for trauma use either anatomically based estimations of injury or presenting vital signs. Markers of organ dysfunction may provide additional prognostic capability to these models. The objective of this study was to evaluate if urinary biomarkers are associated with poor outcomes, including death and the need for renal replacement therapy.MethodsWe conducted a prospective, observational study in United States Military personnel with traumatic injury admitted to the intensive care unit at a combat support hospital in Afghanistan.ResultsEighty nine patients with urine samples drawn at admission to the intensive care unit were studied. Twelve patients subsequently died or needed renal replacement therapy. Median admission levels of urinary cystatin C (CyC), interleukin 18 (IL-18), L-type fatty acid binding protein (LFABP) and neutrophil gelatinase-associated lipocalin (NGAL) were significantly higher in patients that developed the combined outcome of death or need for renal replacement therapy. Median admission levels of kidney injury molecule-1 were not associated with the combined outcome. The area under the receiver operating characteristic curves for the combined outcome were 0.815, 0.682, 0.842 and 0.820 for CyC, IL-18, LFABP and NGAL, respectively. Multivariable regression adjusted for injury severity score, revealed CyC (OR 1.97, 95 % confidence interval 1.26-3.10, p = 0.003), LFABP (OR 1.92, 95 % confidence interval 1.24-2.99, p = 0.004) and NGAL (OR 1.80, 95 % confidence interval 1.21-2.66, p = 0.004) to be significantly associated with the composite outcome.ConclusionsUrinary biomarker levels at the time of admission are associated with death or need for renal replacement therapy. Larger multicenter studies will be required to determine how urinary biomarkers can best be used in future prediction models.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0965-y) contains supplementary material, which is available to authorized users.

Urinary Biomarkers are Associated with Severity and Mechanism of Injury

“…This demonstrates the feasibility of using UBs for estimating injury severity in combat casualties. When these findings are put in the context of our prior work in this cohort showing that UBs predict the combined endpoint of mortality or need for RRT (4), they further the concept that UBs can be used for the estimation of injury severity and risk stratification in the forward-deployed combat environment. In this setting UBs could be used for the purposes of triage and prioritization of evacuation.…”

“…Recruitment and analysis of the military cohort has been previously described (4). In brief, the initial military cohort consisted of 89 injured active duty personnel that met the inclusion criteria from October 2012 to December 2013 admitted to the ICU in Craig Joint Theater Hospital in Afghanistan.…”

“…Descriptive data on demographic variables (age, race, and sex), time to first UB draw following injury, mean arterial pressure (MAP) at ICU admission, AKI, RRT, and mortality were also reported. AKI was defined using an accepted creatinine based criteria (16) as previously described (4). …”

“…The kidneys receive a large portion of cardiac output (3) and are exquisitely sensitive to ischemic injury, making them promising markers for global hypo-perfusion. Indeed, UBs have been demonstrated to correlate with poor outcomes in combat casualties (4). Given the ready availability of urine, even in an austere environment complicated by prolonged evacuation times, UBs have the potential to be a deployable solution to quantify severity of injury and predict risk.…”

“…Recent research has concentrated on the ability of UBs to predict acute kidney injury (AKI), need for renal replacement therapy (RRT) and mortality (4, 7, 8). However, most of these biomarkers are not only associated with AKI, but also with the underlying condition causing the AKI (8).…”