Nephrotoxic Effects of Aminoglycoside Treatment on Renal Protein Reabsorption and Accumulation

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Abstract
To quantify the effects of gentamicin, kanamycin and netilmicin on renal protein reabsorption and accumulation, these drugs were administered to rats i.p. (30 mg/kg per day) for 7, 14 or 21 days. Scanning electron microscopy of the glomerular endothelia, urinary measurements of Na, K, endogenous lysozyme, N-acetyl-.beta.-D-glucosaminidase (NAG) as well as clearance and accumulation experiments after i.v. administration of egg-white lysozyme and measurements of inulin clearance (GFR) were done in each treatment group. Gentamicin administration decreased diameter, density and shape of endothelial fenestrae. Kanamycin and netilmicin appeared to have no effect at the dose used. All 3 aminoglycosides decreased GFR and increased urinary excretion of Na and K. While gentamicin and kanamycin decreased the percentage reabsorption and accumulation of lysozyme after i.v. administration of egg-white lysozyme netilmicin had no effect. Daily excretion of total protein, endogenous lysozyme and NAG increased only after treatment with kanamycin and gentamicin. Thus, aminoglycosides may act as nephrotoxicants at glomerular and/or tubular level inducing impairment of renal reabsorption and accumulation of proteins.