Case of the Month #27 - rhabdomyolysis

Published 02/03/2022

How does rhabdomyolysis cause renal failure?

Creatine kinase (predominantly the MM – skeletal muscle- subtype) is the muscle breakdown product most commonly measured with rhabdomyolysis.  However, CK is a benign enzyme which is easily assayed. It is myoglobin, an oxygen binding intracellular protein that is also released from damaged muscle, that causes renal injury.

Mechanism by which renal failure occurs:1

  • Injured muscle sequesters fluid leading to intravascular volume depletion, which results in ADH release, renin-angiotensin system and sympathetic nervous system activation. These all induce renal artery vasoconstriction and salt and water retention.
  • Myoglobin release causing:
    • Renal vasoconstriction and inhibition of vasodilatation by a direct effect of myoglobin induced oxidative injury due to myoglobin’s Fe2+ haem protein
    • Direct tubular toxicity at the proximal convoluted tubule in the presence of acidic urine.
    • Precipitation of protein complexes formed by myoglobin combining with Tamm-Horsfall proteins (proteins produced by cells in the loops of Henle and excreted into urine) in the distal convoluted tubules (DCT) which cause obstruction of the nephron.
  • Nephrotoxic effects of other breakdown products of muscle cells and acute inflammatory proteins such as TNFα and thromboxane