title: Myoglobinuric acute renal failure in the rat: a role for acidosis?
abstract: Myoglobin induces renal injury by mechanisms that remain incompletely defined. Acidosis has been suggested as an important factor in myoglobinuric 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 vitro. In isolated rat kidneys at normal pH, myoglobin at concentrations of 25-250 mg/dl minimally affected renal perfusion flow, glomerular filtration rate (GFR) and tubular sodium reabsorption (TRNa). By contrast, 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, suggesting 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 control animals by myoglobin infusion (38 mg/100 g body weight), was comparably prevented by both chronic alkalosis and acidosis. Acute intravenous or oral acid load provided similar protection. Thus, although acidosis exacerbates myoglobin toxicity in isolated perfused kidneys, acute 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, endogenous acidosis rather than being an independent risk factor is a marker of tissue hypoperfusion and organism susceptibility to myoglobin renal toxicity.
authors.affiliation: Department of Medicine, Hadassah Hospital, Mt. Scopus, Jerusalem, Israel.
authors.forename: S N
authors.initials: SN
authors.lastname: Heyman
authors.forename: R
authors.initials: R
authors.lastname: Greenbaum
authors.forename: A
authors.initials: A
authors.lastname: Shina
authors.forename: S
authors.initials: S
authors.lastname: Rosen
authors.forename: M
authors.initials: M
authors.lastname: Brezis
mesh_terms: D000136:Acid-Base Equilibrium; D000138:Acidosis / Q000150:complications* / Q000378:metabolism; D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D000818:Animals; D004195:Disease Models, Animal; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D008297:Male; D009212:Myoglobinuria / Q000209:etiology* / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley