Clinical trial NCT06167512: Metabolic Reprogramming in Renal Tubular Cells in Acute Kidney Injury Following Severe Trauma
Official title: Metabolic Reprogramming in Renal Tubular Cells in Acute Kidney Injury Following Severe Trauma
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Multi-organ Failure After Severe Trauma
Keywords: Severe trauma
hemorrhagic shock
Acute kidney Injury
Acute respiratory distress syndrome
Multi-organ failure
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2023-12-12
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: polytrauma patients : a population of severe trauma patients at risk of failure secondary organs.

healthy volonteers

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Profile of urinary metabolite concentrations measured by mass spectometry
timeFrame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
Secondary outcomes:
measure: mitochondrial enzymatic activities of cultured Human Kidney 2 (HK2) kidney cells exposed to patient serum and exposed to serum from healthy volunteers
timeFrame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
measure: mitochondrial membrane potential of cultured Human Kidney 2 (HK2) kidney cells exposed to patient serum and exposed to serum from healthy volunteers
timeFrame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
measure: mitochondrial Adenosine TriPhosphate (ATP) content of cultured Human Kidney 2 (HK2) kidney cells exposed to patient serum and exposed to serum from healthy volunteers
timeFrame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
measure: expression levels of mitochondrial of cultured Human Kidney 2 (HK2) kidney cells exposed to patient serum and exposed to serum from healthy volunteers
timeFrame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
measure: Plasma metabolite concentration profile measured by mass spectrometry
timeFrame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
measure: advanced glycation end products (AGEs) produced by red blood cells
timeFrame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
measure: reactive oxygen derivatives produced by red blood cells
timeFrame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
measure: erythrocyte NO production produced by red blood cells
timeFrame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
measure: haptoglobin level
timeFrame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
measure: haptoglobin-hemoglobin complexes level
timeFrame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
measure: free hemoglobin level
timeFrame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
measure: monocyte CD163 receptor from peripheral blood mononuclear cell (PBMC) isolation level
timeFrame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
measure: Heme oxygenase-1 (HO-1) enzyme catabolizing heme level
timeFrame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
measure: renin-angiotensin-aldosterone (RASS) profile
timeFrame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
measure: Antidiuretic hormone (ADH) profile
timeFrame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
measure: cortisol profile
timeFrame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
measure: leptine profile
timeFrame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
measure: Intensity of renal tubular injury
timeFrame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
measure: hypoxemia level
timeFrame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
measure: use of mechanical ventilation
timeFrame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
measure: Radiographic Assessment of Lung Edema (RALE) score
timeFrame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
measure: alveolar epithelial lesions
timeFrame: On admission, at 12 hours, 24 hours and 48 hours of hospital admission
measure: Death
timeFrame: Day 30
Other outcomes:
Locations:
city: Le Kremlin-Bicêtre
country: France
facility: Bicetre hospital
city: Le Kremlin-Bicêtre
country: France
facility: Bicetre hospital
Study officials:
References: