Physical trauma can affect any individual and is globally accountable for more than one in every ten deaths. Although direct severe kidney trauma is relatively infrequent, extrarenal tissue trauma frequently results in the development of acute kidney injury (AKI). Various causes, including haemorrhagic shock, rhabdomyolysis, use of nephrotoxic drugs and infectious complications, can trigger and exacerbate trauma-related AKI (TRAKI), particularly in the presence of pre-existing or trauma-specific risk factors. Injured, hypoxic and ischaemic tissues expose the organism to damage-associated and pathogen-associated molecular patterns, and oxidative stress, all of which initiate a complex immunopathophysiological response that results in macrocirculatory and microcirculatory disturbances in the kidney, and functional impairment. The simultaneous activation of components of innate immunity, including leukocytes, coagulation factors and complement proteins, drives kidney inflammation, glomerular and tubular damage, and breakdown of the blood–urine barrier. This immune response is also an integral part of the intense post-trauma crosstalk between the kidneys, the nervous system and other organs, which aggravates multi-organ dysfunction. Necessary lifesaving procedures used in trauma management might have ambivalent effects as they stabilize injured tissue and organs while simultaneously exacerbating kidney injury. Consequently, only a small number of pathophysiological and immunomodulatory therapeutic targets for TRAKI prevention have been proposed and evaluated.
Trauma is a major cause of death worldwide. Although direct kidney injury is infrequent, one in four patients with severe injuries subsequently develops trauma-related acute kidney injury (TRAKI).
Trauma management prioritizes stabilizing vital physiological functions; however, several therapeutic interventions, such as mechanical ventilation, mass transfusion or the use of nephrotoxic drugs, which are used to stabilize the patient, often aggravate kidney injury.
TRAKI is a multifaceted syndrome that develops owing to numerous trauma-associated drivers of kidney injury — local and remote tissue damage, hypoxia, microcirculatory disturbances and ischaemia–reperfusion injury, as well as exposure to debris, pathogens and toxins.
Trauma-induced activation of innate immunity also promotes kidney injury — the complement system, the coagulation cascade, leukocytes and platelets function as a first line of defence to limit tissue damage but might also aggravate TRAKI.
The post-trauma immune response can disrupt organ barriers, including the blood–urine barrier, and both the innate immune and the autonomic nervous system are key components of kidney–remote organ crosstalk in TRAKI.
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This review was supported by funding from the German Research Foundation (DFG) to M. H.-L. (CRC 1149, project numbers INST 40/479-2 and INST 40/487-2).
The authors declare no competing interests.
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- Haemorrhagic shock
Life-threatening blood loss with subsequent reduced tissue perfusion and inadequate oxygen supply relative to oxygen requirement.
- Positive end-expiratory pressure
The level of airway pressure in the lungs above ambient pressure at end-expiration.
- Mass transfusion
Transfusion of ≥10 units of packed red blood cells within 24 h.
- Restrictive transfusion
Transfusion initiated when the patient has a total haemoglobin concentration ≤80 g/l and/or the patient develops symptoms of anaemia.
- Liberal transfusion
Transfusion initiated when the patient has a total haemoglobin concentration ≤100 g/l.
- Crush injury
Compression of the limbs and/or torso due to trauma.
Multiple traumatic injuries, of which at least one injury or the combination thereof is life-threatening.
Formation of thrombi initiated by the innate immune response to invading bacteria aimed at local infection control.
- Crush syndrome
Syndrome characterized by degradation of muscle tissue (that is, rhabdomyolysis) accompanied by the accumulation of tissue debris and myoglobin.
- Marginated neutrophils
Neutrophils from the circulating cell pool that attach to surfaces such as the endothelium.
- Post-traumatic abdominal compartment syndrome
Syndrome characterized by post-traumatic intra-abdominal hypertension (that is, intra-abdominal pressure >20 mmHg) and de novo visceral organ dysfunction or failure.
- Neuronal pyknosis
An early hallmark of neuronal cell death characterized by irreversible condensation of chromatin.
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Messerer, D.A.C., Halbgebauer, R., Nilsson, B. et al. Immunopathophysiology of trauma-related acute kidney injury. Nat Rev Nephrol 17, 91–111 (2021). https://doi.org/10.1038/s41581-020-00344-9
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