Studies of mechanisms and protective maneuvers in myoglobinuric acute renal injury

Lab Invest. 1989 May;60(5):619-29.


To explore why urine pH affects myoglobin (M)-induced renal injury, rats were infused with M under aciduric (NH4Cl) or alkalinuric (KHCO3) conditions with or without additional solute loading. Acute renal M retention (R) was highly pH dependent (pH 5.77, 68% R; pH 6.45, 49% R; pH 8.0, 28% R), the % R positively affecting the severity of renal injury (azotemia, proximal tubular necrosis, M casts, medullary vascular congestion, assessed 3 and/or 24 hours later). However, nonreabsorbable, nonalkalinizing salts (SO4) equiosmolar to KHCO3 decreased M retention to 21% and produced comparable functional/morphologic protection as HCO3. Equiosmolar reabsorbable salt (NaCl) did not decrease M retention (67%) or confer significant protection. M, when suspended in urine, but not in 0.45% NaCl, was highly acid precipitable (73% versus 10%). Electrophoretic/solubility studies indicated that M, not hematin, precipitated. M infusion did not decrease renal cortical soluble thiol groups (principally glutathione) or raise malondialdehyde concentrations at a time that tubular damage was apparent. Neither deferoxamine nor 2 hydroxyl radical scavengers (dimethylthiouria, Na benzoate) conferred significant functional/morphologic protection. These results indicate that aciduria promotes myoglobinuric-renal injury by acutely trapping M within the kidney, not by causing hematin formation. HCO3 protects by increasing urinary M solubility and by providing nonreabsorbed solute, both facilitating its excretion. Fe-stimulated hydroxyl radical formation does not appear to be necessary for M to cause renal damage.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Kidney Injury / etiology*
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Animals
  • Disease Models, Animal
  • Female
  • Hydrogen-Ion Concentration
  • Kidney / pathology*
  • Myoglobin / metabolism*
  • Myoglobinuria / complications
  • Myoglobinuria / metabolism*
  • Myoglobinuria / pathology
  • Oxidation-Reduction
  • Rats
  • Rats, Inbred Strains
  • Rhabdomyolysis / metabolism*
  • Solubility


  • Myoglobin