Rhabdomyolysis and Acute Kidney Injury Pathophysiology

Rhabdomyolysis is a clinical syndrome characterised by the breakdown of skeletal muscle fibres and the subsequent release of intracellular constituents into the bloodstream. Central to the cascade is myoglobin, a heme-containing protein that, when present in high concentrations, precipitates in renal tubules, induces oxidative stress and promotes vasoconstriction. Cellular injury in the kidney arises from direct tubular toxicity, intratubular cast formation and ischaemia. Inflammatory mediators released in response to muscle injury amplify endothelial dysfunction, further compromising renal perfusion. The spectrum of aetiologies spans trauma, exertion, metabolic derangement, toxins and inherited myopathies.

Acute kidney injury (AKI) from rhabdomyolysis typically evolves through three overlapping phases: an initial vasoconstrictive phase with hypoperfusion, a second phase of tubular epithelial cell injury and a third reparative phase. Intracellular calcium overload, free‐radical generation and mitochondrial dysfunction play critical roles in tubular cell death. Clinically, the extent of AKI correlates with the degree of myoglobinuria, electrolyte disturbance and systemic inflammatory response. Early recognition and supportive measures, particularly aggressive fluid resuscitation, remain the cornerstones of management to prevent progression towards severe AKI and the need for renal replacement therapy.

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Rhabdomyolysis and Acute Kidney Injury Pathophysiology publication trend

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Technical terms

Rhabdomyolysis: Syndrome of skeletal muscle breakdown leading to release of intracellular proteins and electrolytes.

Myoglobin: Oxygen-binding protein in muscle that, when filtered in excess, causes tubular obstruction and oxidative injury.

Acute kidney injury (AKI): Sudden loss of renal function characterised by elevation of serum creatinine and reduction in urine output.

Oxidative stress: Imbalance between the production of reactive oxygen species and the ability of the body to detoxify them.

Renal replacement therapy (RRT): Extracorporeal techniques, such as dialysis or haemofiltration, used to support kidney function.

References

1. Myoglobin adsorption and saturation kinetics of the cytokine adsorber Cytosorb® in patients with severe rhabdomyolysis: a prospective trial. Annals of Intensive Care (2024).
2. Myoglobin clearance with continuous veno-venous hemodialysis using high cutoff dialyzer versus continuous veno-venous hemodiafiltration using high-flux dialyzer: a prospective randomized controlled trial. Critical Care (2020).
3. Short- and long-term renal outcomes following severe rhabdomyolysis: a French multicenter retrospective study of 387 patients. Annals of Intensive Care (2020).