title: Comparative effects of low- and high-osmolar contrast media on the renal function during early degenerative gentamicin-induced nephropathy in rats.
abstract: The nephrotoxic potentials of a high-osmolar contrast medium, diatrizoate, and of a low-osmolar contrast medium, ioxaglate, were compared during early degenerative gentamicin-induced nephropathy in the rat. Male rats (13-22/group) were uninephrectomized. Six days later, the aorta was clamped above the renal artery, and either diatrizoate or ioxaglate was administered (1 ml/min for 3 min) via an aortic puncture into the remaining kidney. Some of the rats received chronic treatment with gentamicin (50 mg/kg/day i.m., 4 days), starting 2 days before and ending 1 day after contrast medium administration. Two control groups, only one of which received gentamicin, were subjected to a 3-min renal ischemia. The creatinine clearance (CrCl) per 100 g body weight was determined before and 24 and 48 h after contrast medium injection. A second study (6 rats/group) evaluated urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion and the histologic appearance of the kidneys (blinded analysis) in the same experimental groups. Gentamicin induced a significant decrease in CrCl at baseline (0.35 +/- 0.19 vs. 0.41 +/- 0.19 ml/min; p < 0.01) and an increase in urinary NAG (128 +/- 92 vs. 39 +/- 57 mumol/h/mmol creatinine; p < 0.01). Taking into account these differences at baseline, univariate repeated-measures analysis showed that on day 1 diatrizoate caused a more marked decrease in CrCl than ioxaglate (p < 0.05), whether or not gentamicin was also administered. On day 2, the depressant effect of diatrizoate associated with gentamicin persisted (CrCl vs. day 0 = -0.19 +/- 0.10 ml/min), while that of diatrizoate alone returned to baseline (-0.05 +/- 0.24 ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Laboratoire Guerbet, Aulnay-sous-Bois, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Idée
authors.forename: R
authors.initials: R
authors.lastname: Santus
authors.forename: H
authors.initials: H
authors.lastname: Beaufils
authors.forename: C
authors.initials: C
authors.lastname: Balut
authors.forename: A M
authors.initials: AM
authors.lastname: Huntsman
authors.forename: R
authors.initials: R
authors.lastname: Bourbouze
authors.forename: B
authors.initials: B
authors.lastname: Koeltz
authors.forename: C
authors.initials: C
authors.lastname: Jouanneau
authors.forename: B
authors.initials: B
authors.lastname: Bonnemain
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000378:metabolism; D000818:Animals; D003404:Creatinine / Q000378:metabolism; D003973:Diatrizoate / Q000633:toxicity*; D005839:Gentamicins / Q000008:administration & dosage / Q000633:toxicity*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007485:Ioxaglic Acid / Q000008:administration & dosage / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005839:Gentamicins; D003973:Diatrizoate; D003404:Creatinine; D000118:Acetylglucosaminidase; D007485:Ioxaglic Acid