Aminoaciduria is an earlier index of renal tubular damage than conventional renal disease markers in the gentamicin-rat model of acute renal failure.
There are currently no reliable early markers of renal tubular damage. Since aminoaciduria is an accompanying feature of this condition, the usefulness of increased urinary amino acid excretion as a marker was investigated by inducing renal tubular necrosis in male Wistar rats by the administration of gentamicin (40 mg/kg/d) for 14 d. Plasma amino acids, urea, creatinine, protein and electrolytes, and urine amino acids, protein and N-acetylglucosaminidase (a lysosomal enzyme) were measured over a 20 d period. Amino acid excretion increased dramatically within 24 h of the initial dose for 14 of the 16 amino acids measured. The conventional renal disease markers listed above did not increase until after day 7. Glomerular damage caused by puromycin aminonucleoside did not induce aminoaciduria until marked proteinuria occurred (day 9), and even then amino acid excretion was much less than that caused by gentamicin. To distinguish whether the gentamicin-induced aminoaciduria was a consequence of tubular damage or inhibition of amino acid transport, isolated rat kidneys were perfused with a Krebs-Henseleit albumin buffer with and without gentamicin for 20 min, during which time urinary amino acids were quantitated. Gentamicin did not inhibit amino acid reabsorption. Thus, it appears that in the rat-gentamicin model of acute renal failure, urinary amino acids are early markers of renal tubular damage.
Macpherson
N A
NA
Department of Biochemistry, Hospital for Sick Children, Toronto, Ontario.
Moscarello
M A
MA
Goldberg
D M
DM
D000118:Acetylglucosaminidase / Q000652:urine; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000503:physiopathology / Q000652:urine*; D000409:Alanine / Q000652:urine; D000596:Amino Acids / Q000652:urine; D000818:Animals; D015415:Biomarkers; D003404:Creatinine / Q000097:blood / Q000652:urine; D005839:Gentamicins; D005998:Glycine / Q000652:urine; D007684:Kidney Tubules / Q000473:pathology / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D011507:Proteinuria; D011692:Puromycin Aminonucleoside / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014508:Urea / Q000097:blood
D000596:Amino Acids; D015415:Biomarkers; D005839:Gentamicins; D011692:Puromycin Aminonucleoside; D014508:Urea; D003404:Creatinine; D000118:Acetylglucosaminidase; D000409:Alanine; D005998:Glycine