Markers of Tissue Injury and Rhabdomyolysis in Patients With Major Trauma

Major trauma is associated with a release of alarmins (DAMPs - damage-associated molecular patterns) from the injured tissues. This process results in the activation of the immune system, which is one of the main mechanisms participating in the development of organ dysfunctions in patients with major trauma. Limited literary sources describe a correlation between the mitochondrial DNA (mDNA) and the value of plasma creatine kinase (sCK) (which is released from the injured muscles), which suggests a possible correlation between the number of released alarmins and the degree of rhabdomyolysis (damage of striated muscles). Rhabdomyolysis is further - due to the direct nephrotoxicity of myoglobin (sMb) released from the injured muscles - a significant factor participating in the development of acute renal failure in patients with serious injuries. Considering the fact that the serious injury need not include a vast damage of the muscle mass (especially in traumas with a minimal impairment of extremities), the correlation between the DAMPs and sCK/sMb values need not be constant in relation to the extent and localization of the injury defined with the AIS (Abbreviated Injury Scale) and ISS (Injury Severity Scale) scales. The DAMPs released from injured tissues immediately after trauma include HMGB-1 (high mobility group box 1); a correlation has been observed between the early post-injury levels of HMGB-1 and unfavorable outcome (defined with development of organ dysfunctions and increased mortality). Considering the fact that the DAMPs examination (including HMGB-1) are routinely available, and are also rather expensive, they are not a standard part of examinations performed in patients with serious trauma. Determination of correlation between HMGB-1 and the routinely available examinations of sCK and sMb would make the use of sCK and sMb examinations as direct indicators of mechanical tissue damage. Furthermore, this data has a significant descriptive impact in case of direct inclusion of sCK and sMb into predictive scoring systems, which currently do not contain relevant physiological parameters correlating with the extent of the injury.

In the second part of the study, the authors will concentrate upon evaluation of correlation of HMGB-1, serum creatine kinase and serum myoglobin in relation to the development of acute kidney injury (AKI), and in relation to the values of AKI markers, specifically NGAL (neutrophil-gelatinase associated lipocalin). The currently used AKI criteria are based upon relatively imprecise and late parameters (urine output, level of serum creatinine), and that is why AKI is identified in the clinical practice only in the stage of advanced and irreversible morphological and functional changes of kidneys.

The aims of the study are the following:

• To verify the correlation between the levels of circulating alarmins (HMGB-1) and the levels of sCK and sMb
• To identify the correlation between the levels of circulating alarmins and localization of the injury (according to AIS and ISS scoring systems)
• Mutual comparison of predictive levels of sCK and sMb in relation to the development of post-injury kidney failure
• Mutual comparison of predictive levels of sCK and sMb in relation to the serum and urine levels of AKI biomarkers
• Comparison of predictive levels of serum and urine NGAL in relation to the development of post-injury AKI