Metabolic Reprogramming in Renal Tubular Cells in Acute Kidney Injury Following Severe Trauma

Metabolic Reprogramming in Renal Tubular Cells in Acute Kidney Injury Following Severe Trauma

Severe trauma remains the leading cause of death in people under 50, and is associated with high morbidity, including severe disability, with a substantial socio-economic impact. Secondary to trauma, multiple mechanisms (inflammatory, ischemic, oxidative, etc.) setting in rapidly, leads to organ failure, one of the three first cause of death. Vascular damage, with vasoplegia, renal damage, with acute kidney injury (AKI), and pulmonary damage, with acute respiratory distress syndrome (ARDS), are the most frequently observed but all organs can be affected whatever the type of trauma. For these reasons, identifying the pathophysiological pathways involved in organ failure induced by severe trauma is a major step towards limiting the morbidity and mortality induced by trauma, and proposing therapies to prevent them.

Because of the variability of lesions in these patients, and the multiplicity of pathways activated, the mechanisms involved and their causality with organ failure following severe trauma, are still poorly understood. Given their frequency and importance in terms of morbidity and mortality, the investigators decided to take a particular interest in the mechanisms leading to renal and pulmonary injury. The investigators' hypothesis is that the study of urinary and blood markers not performed as part of clinical routine would provide a better understanding of the pathophysiological mechanisms leading to organ failure secondary to severe trauma, and more specifically to renal and pulmonary injuries. With TRAUMATEC study, the investigators will explore mechanisms leading to AKI and ARDS through blood and urine samples of 60 severe trauma patients sampled over the first 48 hours after ICU admission and a reference of 20 healthy volunteers.

The investigators plan to include 60 patients over 18 years old with severe trauma, defined with an ISS≥9 and 20 healthy volunteers 18 years old as a reference group.

Blood and urine samples will be collected at ICU arrival, 12-, 24- and 48- hours after ICU admission. Specific dosages will then be realized on blood and urines to study metabolic and hormonal pathway leading to AKI and ARDS.

The primary objective of the study is to explore the association between renal metabolic changes and renal function impairment following severe trauma.

Secondary objectives are (1) to explore mitochondrial changes observed at the renal cellular level, on in vitro renal culture cells after exposure to trauma patient serum (2) to explore the association between plasma metabolic changes and renal and pulmonary function impairment following severe trauma (3) to explore the association between hormonal metabolic changes and renal and pulmonary function impairment following severe trauma (4) to explore the association between red blood cell-induced oxidative stress and renal function impairment following severe trauma (5) to explore the association between changes in the hemoglobin recycling (chelation) system and impaired renal function following severe trauma (6) to explore renal tubular damage secondary to severe trauma (7) to explore the pathophysiological mechanisms associated with pulmonary damage following severe trauma (8) to describe mortality at day 30.

Inclusion Criteria:

Trauma patients :

• Adult patients (age ≥ 18 years)
• Patient admitted for suspected severe trauma (1 Vittel criteria)
• Injury Severity Score ≥ 9
• Health insurance
• Written consent obtained from the patient or trusted support person / family member / close friend, or inclusion in an emergency situation and written consent obtained from the patient (trusted support person / family member / close friend if necessary) as soon as possible (article L1122-1-2 of the CSP).

Healthy volunteers :

• Adult patients (≥ 18 years)
• Affiliated with health insurance
• Written informed consent́
• Patient respecting matching

Exclusion Criteria:

Trauma patients :

• Pregnant patient
• Minor patient
• Adult under guardianship, curatorship or safeguard of justice
• Patient under Aide Médicale d'État
• Chronic renal failure on dialysis
• Chronic respiratory disease
• Patient with chronic cardiac insufficiency
• Systemic inflammatory disease

Healthy volunteers :

• Pregnant patient
• Minor patient
• Adult under guardianship, curatorship or safeguard of justice
• Patient under Aide Médicale d'État
• Patient with chronic renal failure on dialysis
• Chronic respiratory disease
• Patient with chronic cardiac insufficiency
• Systemic inflammatory disease