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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

Tatjana Vujić, Snežana Uletilović, Jelica Predojević-Samardžić, Biljana Davidović-Plavšić, Svjetlana Stoisavljević-Šatara and Živko Saničanin

The Activity of Proximal Tubule Enzymes in the Urine of Cephalexin-Treated Patients

The activities of alanine aminopeptidase (AAP), γ-glutamyltransferase (GGT) and N-acetyl-β-D-glucosaminidase (NAG), enzymes dominantly localised in the epithelial proximal tubule cells, were measured with an aim of determining the nephrotoxicity of a cephalosporin antibiotic cephalexin. Enzymatic activities were measured in the 12-h urine samples of patients receiving cephalexin orally for 15 days in daily doses of 50 mg/kg body mass against Gram-positive infections of the respiratory or urinary tract. The same enzymes were determined in the 12-h urine samples of the corresponding control. Both the control and the experimental group consisted of 30 examinees of both sexes, age range 3-10 years. Statistically significant differences in AAP and GGT activities expressed as U/mmol creatinine were recorded after 12 days of cephalexin therapy in comparison with the control (p < 0.01). At the same time, no significant differences in NAG activity of the patients in relation to the control were observed during the entire course of the therapy. Based on the obtained results it can be concluded that treatment of 3-10 years old patients with the applied cephalexin doses for 15 days results in mild nephrotoxic changes close to the end of therapy accompanied by increased activities of AAP and GGT, the enzymes known as very sensitive indicators of nephrotoxicity. The results showing that during the entire period of cephalexin application no changes in NAG, as a lysosomal enzyme, were observed, could be taken as a proof that this antibiotic did not lead to severe injuries of epithelial proximal tubule cells at the level of cell organelles.

Open access

Ljiljana Popović, Katarina Lalić, Olga Vasović, Danijela Drašković Radojković, Nataša Rajković, Sandra Singh, Ljubica Stošić, Miodrag Čivčić, Ljiljana Škorić Hinić and Tatjana Petrović Vujić

Summary

Background: Previous studies have indicated that high sensitivity C-reactive protein (hs-CRP) is a risk factor for the peripheral arterial disease (PAD) in diabetes. This study aimed to evaluate the possible predictive significance of hs-CRP for the development and progression of PAD in patients with type 2 diabetes (T2D).

Methods: The study included 80 patients previously diagnosed with T2D, aged 45–70 years, divided into group A (T2D patients with PAD; n=38) and group B (T2D patients without PAD; n=42). After five years, all the patients were re-examined and divided into subgroups depending on de novo development of PAD or progression of previously diagnosed PAD. Ankle-Brachial Index (ABI) measurement was used for PAD diagnosis and hs-CRP was determined by nephelometry.

Results: We found significantly higher hs-CRP levels in group A compared to group B, but only at baseline. Among the patients in group A, those with later progression of PAD (subgroup A1) had the highest levels of hs-CRP at baseline, although not significantly different from those in subgroup A2 (non-progressors). In contrast, hs-CRP level was significantly higher in subgroup B1 (progressors) in comparison to subgroup B2 (non-progressors) at both the first and second exam. Of all the investigated metabolic parameters, hs-CRP was the only independent predictor of PAD progression (OR=0.456, 95% CI=0.267–0.7815, p=0.004). The cut-off point for hs-CRP was 2.5 mg/L (specificity 75% and sensitivity 73.3%) with the relative risk for PAD of 2.93 (95% CI=1.351–6.3629).

Conclusions: Our study implies that hs-CRP can be used as a reliable predictor for the progression of PAD in patients with T2D.