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Biljana Davidović-Plavšić, Tatjana Vujić, Snežana Uletilović, Jelica Predojević-Samardžić, Dragana Malčić and Živko Saničanin

Urinary Activities of Proximal Tubule Enzymes in Neonates Treated with Gentamicin

In order to determine the nephrotoxicity of gentamicin, an aminoglycoside antibiotic, activity of the enzymes dominantly localized in proximal tubules, i.e. alanine aminopeptidase (AAP), γ-glutamyl transferase (GGT) and N-acetylβ-D-glucosaminidase (NAG) was examined. Determinations were performed in 12-h urine samples of 30 neonates i.v. receiving gentamicin against Gram negative infections in daily doses of 5.0 mg/kg body mass for 10 consecutive days. The activities of the same enzymes were measured in 12-h urine samples of 30 examinées of the control group. The groups consisted of neonates of both sexes. The pretreatment period lasted for 5 days. On day 8 of gentamicin application, statistically significant differences in the activity of AAP and GGT expressed in U/mmol creatinine between the gentamicin-receiving and control group (p<0.01) were found. No significant differences in NAG activity of the gentamicin-treated group in comparison with the control were recorded during the 10-day gentamicin therapy. It can be concluded that 10-day treatment of neonates with usually prescribed gentamicin doses results in mild nephrotoxic changes close to the end of the therapy accompanied by increased activity of both urinary AAP and GGT, known as very sensitive indicators of nephrotoxicity. During the same treatment period no changes in NAG activity were observed, meaning that the antibiotic causes no severe injuries to proximal tubule cells at the level of cellular organelles.

Open access

Biljana Davidović, Jelica Predojević-Samardžić, Snežana Uletilović, Dragana Malčić and Živko Saničanin

Activities of Proximal Tubule Enzymes In Urine of Patients Treated With Gentamicin

The activities of the enzymes dominantly localized within the proximal tubules, such as alanine aminopeptidase (AAP), gamma-glutamyl transferase (GGT) and Nacetyl-beta-D-glucosaminidase (NAG), were measured in 12-h urine samples of patients suffering from Gram-negative infections and i.v. treated with gentamicin with the aim of determining the nephrotoxicity of this aminoglycoside antibiotic. The examined groups consisted of 3 - 10 years old children of both sexes, gentamicin-treated, and the control group, each including 30 patients. Urine samples were collected and analyzed five days before the gentamicin application and during the following 10 days of gentamicin treatment (a single i.v. injection per day in the dose of 2.5 mg/kg b.w.). Significant differences in the AAP and GGT activities expressed in U/mmol creatinine were observed between the gentamicin-treated group and the controls already on day 2 (p < 0.05) of the treatment, as well as in the activity of NAG on day 8 (p < 0.01) of the therapy. From these results it can be concluded that even standard gentamicin doses expressed nephrotoxic effects. Statistically significantly increased AAP and GGT activities in the gentamicin-treated group of children recorded already on the 2nd day of treatment demonstrate that these two enzymes represent extremely sensitive indicators of nephrotoxicity. On the other hand, statistically significantly increased NAG activity observed in the gentamicin-receiving group points to more severe gentamicin-provoked injuries of proximal tubules.