Abstract
The Activity of Proximal Tubule Enzymes in the Urine of Cephalexin-Treated PatientsThe 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.
Highlights
Cephalexin represents a semisynthetic first generation cephalosporin antibiotic, applied in the therapy of moderate respiratory and urogenital infections
Summary: The activities of alanine aminopeptidase (AAP), g-glutamyltransferase (GGT) and N-acetyl-b-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
Summary
Cephalexin represents a semisynthetic first generation cephalosporin antibiotic, applied in the therapy of moderate respiratory and urogenital infections. Different from aminoglycoside antibiotics, its nephrotoxicity in humans as well as that of other cephalosporins was very seldom emphasized in scientific and professional publications. The nephrotoxicity of cephalexin was first examined in experimental animals [1, 2]. Investigations performed during the last decade clearly demonstrated that cephalexin can provoke in some patients acute tubular necrosis, primarily acute tubulointerstitial nephritis [3,4,5]. Tubular necrosis results from changes in the cell membranes of proximal tubules leading to disturbances in organic ion transport across the cell membranes [6,7,8] due to the antibiotic binding to protein carriers of organic ions, acylation of target proteins involved in the transport and lipid peroxidation [9]
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