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

INTRODUCTION: Traditional 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. METHODS: We 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. RESULTS: Eighty 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. CONCLUSIONS: Urinary 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.

Early acute kidney injury in military casualties.

BACKGROUND: While acute kidney injury (AKI) has been well studied in a variety of patient settings, there is a paucity of data in patients injured in the course of the recent wars in Iraq and Afghanistan. We sought to establish the rate of early AKI in this population and to define risk factors for its development. METHODS: We combined the results of two studies performed at combat support hospitals in Afghanistan. Only US service members who required care in the intensive care unit were included for analysis. Data on age, race, sex, Injury Severity Score (ISS), first available lactate, and requirement for massive transfusion were collected. Univariate analyses were performed to identify factors associated with the subsequent development of early AKI. Multivariable Cox regression was used to adjust for potential confounders. RESULTS: The two observational cohorts yielded 134 subjects for analysis. The studies had broadly similar populations but differed in terms of age and need for massive transfusion. The rate of early AKI in the combined cohort was 34.3%, with the majority (80.5%) occurring within the first two hospital days. Patients with AKI had higher unadjusted mortality rates than those without AKI (21.7% vs. 2.3%, p < 0.001). After adjustment, ISS (hazard ratio, 1.02; 95% confidence interval, 1.00-1.03; p = 0.046) and initial lactate (hazard ratio, 1.16; 95% confidence interval, 1.03-1.31; p = 0.015) were independently associated with the development of AKI. CONCLUSION: AKI is common in combat casualties enrolled in two prospective intensive care unit studies, occurring in 34.3%, and is associated with crude mortality. ISS and initial lactate are independently associated with the subsequent development of early AKI. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III.

Anaphylactoid reaction during first hemofiltrationwith a PUREMA polysulfone membrane.

Adverse reactions during hemodialysis are extremely common and include a wide range of clinical presentations from mild to life threatening. We present a case of a 34 year old woman in the Burn Intensive Care Unit, who developed acute kidney injury requiring renal replacement therapy. She was placed on continuous veno-venous hemofiltration with the NxStage machine which uses a synthetic PUREMA polyethersulfone filter sterilized by gamma radiation. Within two minutes of initiating hemofiltration, the patient complained of pruritus as well as dyspnea and became flushed and agitated. She subsequently developed hypotension ultimately resulting in cardiopulmonary arrest. Cardiopulmonary resuscitation was initiated and the patient was given epinephrine with return of spontaneous circulation. The following day, the patient was rechallenged with a PUREMA filter, and had a similar reaction with flushing, dyspnea, pruritus and hypotension requiring treatment to be discontinued. The patient was transitioned to the Prismaflex filter, another synthetic membrane, which she tolerated well and continued to utilize through the remainder of her hospital course without complication. Her clinical presentation was consistent with an anaphylactoid reaction, though a tryptase level was not obtained and a radioallergosorbent test performed with membrane material was negative. This case shows the difficulty of identifying the cause of hypersensitivity reactions involving synthetic membranes not sterilized by ethylene oxide, a commonly use sterilizing agent known to cause hypersensitivity reactions. This rare, but potentially fatal reaction has not previously been reported with a PUREMA filter and this case should raise awareness of hypersensitivity reactions with this widely used method of renal replacement therapy.

Retrospective review of serum creatinine and creatinine-based measures of estimated glomerular filtration rate in an amputee population.

A variety of equations are used to estimate glomerular filtration rate (eGFR). These formulas have never been validated in the setting of traumatic amputation. In this retrospective study involving 255 military personnel with traumatic amputations at a single outpatient center, muscle mass lost was estimated using percentage of estimated body weight lost (% EBWL). Serum creatinine (Scr) and eGFR by the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations were compared to % EBWL for each patient. The average Scr for the group studied was also compared with a cohort matched for age, sex, and race from the Third National Health and Nutrition Examination Survey (NHANES III). Percentage EBWL correlated significantly with Scr (R2 = 0.095, p < 0.0001), eGFR by MDRD (R2 = 0.077, p < 0.0001), and eGFR by CKD-EPI (R2 = 0.074, p < 0.0001). The average Scr was significantly lower than a similar population from NHANES III (0.83 +/- 0.137 mg/dL vs. 1.14 +/- 0.127 mg/dL, p < 0.0001). Percentage EBWL has a significant correlation with Scr and eGFR by both the MDRD and CKD-EPI equations. Furthermore, patients with traumatic amputation have significantly lower Scr values than the general population. Creatinine-based estimators of GFR may overestimate renal function in the setting of traumatic amputation.