Laboratory Investigation

Kidney International (1985) 28, 106–113; doi:10.1038/ki.1985.128

Increased nephrotoxicity of gentamicin in pyelonephritic rats

Denis Beauchamp1, André Poirier1 and Michel G Bergeron1

1Infectious Diseases Service, Le Centre Hospitalier de l'Université Laval, Québec, Québec, Canada

Correspondence: Dr M G Bergeron Chief, Infectious Disease Service, Le Centre Hospitalier de l'Université Laval, 2705 Laurier Blvd., Québec, P.Q., G1V 4G2, Canada

Received 29 June 1984; Revised 19 December 1984.

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Abstract

Increased nephrotoxicity of gentamicin in pyelonephritic rats. Multiple factors may increase the nephrotoxic potential of aminoglycosides. We studied gentamicin susceptibility of kidneys infected with E. coli. Several parameters of renal function, histological changes on light and electron microscopy, and drug levels in renal parenchyma were compared in pyelonephritic and normal rats treated with low doses (10 mg/kg/Q8 hr for 3 days), or high doses (60 mg/kg/day for 14 days), of gentamicin. A significant increase (P < 0.01) in beta-galactosidase and protein excreted in urine over a period of 17 days associated with severe changes in diuresis and osmolality was noted in the infected treated rats (low doses) compared with normal, treated, infected or control animals. Histological modifications compatible with gentamicin nephrotoxicity were more persistent in the infected treated animals. A significant decrease in 14C inulin (P < 0.01) and 3H-PAH clearance and secretion (P < 0.02) was observed in the infected treated rats receiving high doses of antibiotics. Cellular necrosis and tubular desquamation also were more severe in this group. Gentamicin levels in the cortex and medulla of infected animals were significantly higher than in the normals (P < 0.01) and might have been responsible for the increased toxicity noted in the pyelonephritic animals. Infected kidneys appeared to be more susceptible to the nephrotoxic potential of gentamicin.

Néphrotoxicité accrue de la gentamicine chez des rats pyélonéphritiques. De multiples facteurs peuvent accroître le potentiel néphroxique des aminoglycosides. Nous avons étudié la susceptibilité à la gentamicine de reins infectés par E. coli. Différents paramètres de la fonction rénale, les changements histologiques en microscopie optique et électronique, et les niveaux de médicament dans le parenchyme rénal ont été comparés chez des rats pyélonéphritiques ou normaux, traités par de faibles doses (10 mg/kg/8h pendant 3 jours), ou de fortes doses (60 mg/kg/jour pendant 14 jours) de gentamicine. Une élévation significative (P < 0,01) de la beta-galactosidase et des protéines excrétées dans les urines sur une période de 17 jours, associées à des modifications sévères de la diurèse et de l'osmolalité ont été notées chez les rats infectés traités (faibles doses), par rapport aux animaux normaux infectés et traités, ou aux contrôles. Des modifications histologiques compatibles avec une néphrotoxicité à la gentamicine ont été plus persistantes chez les animaux infectés traités. Une baisse significative de la clearance et la sécrétion de 14C inuline (P < 0,01) et de 3H-PAH (P < 0,02) a été observée chez les rats infectés et traités recevant les fortes doses d'antibiotique. La nécrose cellulaire et la desquamation tubulaire étaient également plus sévères dans ce dernier groupe. Les niveaux de gentamicine dans le cortex et la médullaire des animaux infectés étaient significativement plus hauts que chez les normaux (P < 0,01) et pourraient avoir été responsables de l'augmentation de toxicité notée chez les animaux pyélonéphritiques. Les reins infectés apparaissaient plus susceptibles au potentiel néphrotoxique de la gentamicine.

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