Complete protection from gentamicin-induced acute renal failure in the diabetes mellitus rat

Complete protection from gentamicin-induced acute renal failure in the diabetic rat. The possible protective effect of solute and water diuresis on the development of acute renal failure (ARF) following administration of gentamicin, 40 mg/kg of body wt per day for 14 days, was studied in unanesthetized rats. Adult female Sprague-Dawley rats with streptozotocin-induced diabetes mellitus (DM) and rats with hereditary diabetes insipidus (DI) were used as models of chronic solute and water diuresis, respectively. Aged-matched Sprague-Dawley (C) and heterozygous Brattleboro (BC) rats were the respective controls. Because of higher creatinine clearance (C Cr ) in the DM rats, another DM group received a higher dose of gentamicin (DM-H), 70 mg/kg/day for 14 days. C and DM animals injected with Ringer's were SHAM-C and SHAM-DM groups. Following gentamicin, C rats developed ARF (maximal decrease in C Cr from baseline was 85 ± 6(SEM)%; P Cr , lysozymuria, and tubular necrosis. SHAM-C and DM rats maintained unchanged renal function throughout. The kidney content of gentamicin analyzed on day 15 of the study was significantly lower in the DM and DM-H rats than in C, while no differences were found between BC and DI rats. In a separate group of Sprague-Dawley C and DM rats, renal cortical gentamicin content was measured 3, 6, and 9 days after beginning gentamicin administration at 40 mg/kg/day. By day 3 the DM rats had a cortical gentamicin content that was three-fold lower (164 ± 18 µg/g wet tissue) than that of C animals (523 ± 55; P Protection complete contre l'insuffisance renale aigue induite par la gentamicine chez le rat ayant un diabete sucre. Un effet possible d'une diurese d'eau et de solutes sur le developpement de l'insuffisance renale aigue (IRA) par administration de gentamicine, 40 mg/kg/j pendant 14 jours etait etudie, chez des rats non anesthesies. Des rats femelles adultes Sprague-Dawley ayant un diabete sucre (DS) induit par la streptozotocine, et des rats ayant un diabete insipide (DI) hereditaire ont ete utilises comme modele de diurese chronique de solutes et de diurese aqueuse respectivement. Des rats Sprague-Dawley (C) du meme âge, et des rats Brattleboro (BC) heterozygotes ont servi respectivement de controle. En raison de la plus grande deblaiement de creatinine (C Cr ) des rats DS, un autre groupe de rats DS a recu une plus forte dose de gentamicine (DS-H), 70 mg/kg/j/14 jours. Des animaux C et DS recevant du Ringer ont servi de groupes controles. Apres la gentamicine, chez les rats C, sont apparues une IRA (abaissement maximum de C Cr de 85 ± 6%SEM a partir de la valeur de base, P Cr (56 ± 7%, P