Acute amino acid nephrotoxicity.
Previous clinical and experimental data suggest that a limited number of AAs with particular molecular characteristics can adversely affect renal function. The present investigation was conducted to better define the scope and the molecular basis of this nephrotoxicity. Sprague-Dawley rats (N = 31) undergoing a solute diuresis were subjected to 80 min infusions (125 mumol/kg/min) of cationic AAs (lysine, arginine), anionic AAs (glutamic acid, aspartic acid), or neutral AAs (alanine, glycine). Rats infused for 80 min with equimolar amounts of urea or dextrose served as controls (N = 8). GFR (Cioth) were measured 40 min before, during, and 140 min after these infusions. Albumin excretion rates were determined by radioimmunoassay. All AA infusates induced significant (p less than 0.001) reductions in GFR compared to the control infusates (cationic AAs: 62% +/- 4; anionic AAs: 57% +/- 5; neutral AAs: 33% +/- 1; controls: 8% +/- 4) (X +/- S.E.M.). However, only cationic AAs induced a significant increase in albumin excretion (360% +/- 72; p less than 0.001). AA-treated rats had histologic changes with mild tubular injury compared to control rats. These data indicate the following. (1) AAs have in common a nephrotoxic potential. (2) This nephrotoxicity arises, in part, from the nonvariable portion of AA molecules since glycine, which has no variable (R) group, induced a significant reduction in GFR (32% +/- 1). (3) The ability of AAs to decrease GFR is enhanced by certain R groups. However, R group charge is not a critical factor in producing this response. (4) AA-induced increments in albumin excretion and reductions in GFR must arise via independent mechanisms. Since AA infusions are commonly used in patients with ARF the possibility that such therapy might have a deleterious effect on renal function and on the subsequent recovery from ARF should be entertained.
D058186:Acute Kidney Injury / Q000139:chemically induced*; D000409:Alanine / Q000008:administration & dosage / Q000633:toxicity; D000419:Albuminuria / Q000503:physiopathology; D000596:Amino Acids / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000633:toxicity; D001224:Aspartic Acid / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D005919:Glomerular Filtration Rate; D005971:Glutamates / Q000008:administration & dosage / Q000633:toxicity; D005998:Glycine / Q000008:administration & dosage / Q000633:toxicity; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects*; D008239:Lysine / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D014563:Urodynamics
D000596:Amino Acids; D005971:Glutamates; D001224:Aspartic Acid; D001120:Arginine; D008239:Lysine; D000409:Alanine; D005998:Glycine