Nephrotoxic Effects of Aminoglycoside Treatment on Renal Protein Reabsorption and Accumulation

Cojocel, Constantin; Dociu, N.; Ceacmacudis, E.; Baumann, Karl

doi:10.1159/000183225

Cited by 21 publications

(8 citation statements)

References 19 publications

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“…It is well established that rats with streptozotocin-induced DM exhibit a significant proteinuria compared with nondiabetic animals (26, 27), and that protein excretion increases in nondiabetic rats following the administration of gentamicin (27)(28)(29). In 6-hr perfusion studies in vivo, Pattyn et al (25) demonstrated that the renal cortical uptake of gentamicin was reduced in diabetic rats with modest proteinuria in comparison to control animals.…”

Section: Discussionmentioning

confidence: 99%

Insulin Reverses the Protection Given by Diabetes Against Gentamicin Nephrotoxicity in the Rat

Gouvea

Roth

Alpert

et al. 1994

Experimental Biology and Medicine

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Rats with untreated diabetes mellitus are protected from gentamicin-induced nephrotoxicity. In order to evaluate the role of hyperglycemia, glycosuria, and polyuria in this phenomenon, miniosmotic pumps filled with insulin were implanted for 15 days in seven female Sprague-Dawley rats with streptozotocin-induced diabetes mellitus. Plasma glucose levels were successfully maintained under 126 mg/dl. To serve as the control group, eight age-matched diabetic (plasma glucose > 400 mg/dl) rats had miniosmotic pumps placed delivering only Ringer's solution. Six days after placement of the pumps, gentamicin (40 mg/Kg/day) was administered to all animals for 9 days. The insulin-treated diabetic rats exhibited clear signs of nephrotoxicity by Day 6 of gentamicin, whereas the diabetic control group remained free from any functional or morphological evidence of proximal tubular damage throughout the 9 days of the aminoglycoside administration. At the end of the experiment, the creatinine clearance in the insulin-treated diabetic group was 45% lower than in the untreated diabetic group (P < 0.005). In addition, there was a rise in plasma creatinine (P < 0.02), muramidase appeared in the urine, and mild patchy acute tubular necrosis of the renal cortex was observed by light microscopic examination. The insulin-treated group also accumulated more gentamicin in the renal cortex than the untreated animals (P < 0.005). It is concluded that protection against the nephrotoxic effects of gentamicin is a feature of untreated experimental diabetes mellitus in the rat and that correction of the hyperglycemic state with insulin reverses this resistance.

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Section: Discussionmentioning

confidence: 99%

Insulin Reverses the Protection Given by Diabetes Against Gentamicin Nephrotoxicity in the Rat

Gouvea

Roth

Alpert

et al. 1994

Experimental Biology and Medicine

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“…In both humans and animals, lysosomal phospholipidosis results in cell necrosis and alterations in epithelial cells of proximal tubules and to a lesser extent in distal tubules and collecting ducts. Cojocel et al (1984[13]) has shown that GM decrease level of glomerular filtration, as well as tubular reabsorption, leading to accumulation of low molecular weight proteins along with increased renal excretion of sodium and potassium. In physiological conditions these proteins are freely filtered in glomerulus and completely reabsorbed in tubules.…”

Section: Tubular Effectsmentioning

confidence: 99%

Gentamicin nephrotoxicity in animals: current knowledge and future perspectives

Randjelović

Veljković

Stojiljković

et al. 2017

EXCLI Journal; 16:Doc388; ISSN 1611-2156

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“…Urinary NAG has been widely used as a marker of renal tubular damage caused by aminoglycosides in rats (20)(21)(22). Plasma (blood sample obtained by cardiac puncture) and urine concentrations of creatinine were determined on Day 0 to calculate the pretreatment creatinine clearance.…”

Section: Methodsmentioning

confidence: 99%

Comparative study of aminoglycoside nephrotoxicity in normal rats and rats with experimental cirrhosis

Camps¹,

Sola²,

Rimola³

et al. 1988

Hepatology

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Several authors have suggested that the risk of developing aminoglycoside nephrotoxicity is greater in cirrhotic patients than in the noncirrhotic population. However, this has not been confirmed by other investigators. To compare the intensity and characteristics of aminoglycoside nephrotoxicity in cirrhotic and normal rats, 31 rats with carbon tetrachloride-induced cirrhosis with ascites and 35 control rats were treated with gentamicin. Each group of rats was divided into two subgroups in order to receive 10 or 40 mg per kg per day of gentamicin, and different subsets of animals were killed on Days 4, 8 and 12 of treatment for renal histological examination and determination of renal tissue gentamicin concentration. Urine volume, osmolality, sodium excretion and N-acetyl-beta-D-glucosaminidase activity were measured daily throughout the study. Creatinine clearance and trough plasma concentration of gentamicin were determined in each animal immediately before killing. There were no significant differences between cirrhotic and control rats in relation to the magnitude of changes in urine volume, osmolality, sodium excretion and N-acetyl-beta-D-glucosaminidase activity and creatinine clearance during gentamicin administration. The values of a histopathological score semiquantitatively assessing the renal morphological changes observed by light microscopy were not significantly different in cirrhotic and control rats. In addition, similar trough plasma and renal cortical tissue concentrations of gentamicin were observed in both groups of animals. These results suggest that, in this experimental model, cirrhosis does not increase the risk for aminoglycoside nephrotoxicity.

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Nephrotoxic Effects of Aminoglycoside Treatment on Renal Protein Reabsorption and Accumulation

Cited by 21 publications

References 19 publications

Insulin Reverses the Protection Given by Diabetes Against Gentamicin Nephrotoxicity in the Rat

Insulin Reverses the Protection Given by Diabetes Against Gentamicin Nephrotoxicity in the Rat

Gentamicin nephrotoxicity in animals: current knowledge and future perspectives

Comparative study of aminoglycoside nephrotoxicity in normal rats and rats with experimental cirrhosis

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