MYOGLOBINURIC ACUTE-RENAL-FAILURE IN THE RAT - A ROLE FOR ACIDOSIS

Myoglobin induces renal injury by mechanisms that remain incompletely defined. Acidosis has been suggested as an important factor in myoglob inuric renal failure, and urine alkalization is routinely recommended for its prevention. We tested this hypothesis by exploring the effects of acid-base balance upon myoglobin nephrotoxicity in vivo and in vit ro. In isolated rat kidneys at normal pH, myoglobin at concentrations of 25-250 mg/dl minimally affected renal perfusion flow, glomerular fi ltration rate (GFR) and tubular sodium reabsorption (TRNa). By contras t, at pH 7.1 myoglobin induced vasoconstriction, reduced GFR and TRNa and increased hypoxic injury to medullary thick ascending limbs. These changes were largely reproduced by perfusing kidneys with hematin, su ggesting its release from myoglobin in acidosis. Chronic alkalosis or acidosis was induced in rats by supplementing drinking water with 0.28 M NaHCO3 or NH4Cl, respectively. Acute renal failure, produced in con trol animals by myoglobin infusion (35 mg/100 g body weight), was comp arably prevented by both chronic alkalosis and acidosis. Acute intrave nous or oral acid load provided similar protection. Thus, although aci dosis exacerbates myoglobin toxicity in isolated perfused kidneys, acu te or chronic exogenous acid load prevents renal damage in vivo. This may underscore the protective properties of solute load, a consequence of preconditioning, and suggests that, in the crush syndrome, endogen ous acidosis rather than being an independent risk factor is a marker of tissue hypoperfusion and organism susceptibility to myoglobin renal toxicity.