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

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. Aktivnost Enzima Proksimalnih Tubula u Urinu Pacijenata Tretiranih Cefaleksinom Radi određivanja nefrotoksičnosti cefalosporinskog antibiotika cefaleksina, praćena je aktivnost enzima dominantno lokalizovanih u ćelijama epitela proksimalnih tubula, alaninaminopeptidaze (AAP), gama-glutamil-transferaze (GGT) i N-acetil-beta-D-glukozaminidaze (NAG). Određivanje aktivnosti enzima je vršeno u uzorcima 12-časovnog urina kod 30 ispitanika kojima je, zbog grampozitivnih infekcija respiratornog i urinarnog trakta, per os apliciran cefaleksin u dozama od 50 mg/kg telesne mase dnevno za vreme sprovođenja terapije do 15 dana. Aktivnosti istih enzima su određivane i u 12-časovnom urinu 30 ispitanika kontrolne grupe. I eksperimentalna i kontrolna grupa sastojale su se od ispitanika oba pola, starosti od 3 do 10 godina. Statistički značajne razlike u aktivnostima AAP i GGT, izražene u U/mmol kreatinina, registrovane su između ispitanika eksperimentalne i ispitanika kontrolne grupe nakon dvanaestog dana sprovođenja terapije (p < 0,01). Aktivnost NAG ispitanika eksperimentalne grupe u odnosu na ispitanike kontrolne grupe se nisu značajno menjale za čitavo vreme petnaestodnevne terapije. Može da se zaključi da petnaestodnevni tretman ispitanika starosti od 3 do 10 godina preporučenim dozama cefaleksina izaziva blage nefrotoksične promene pri kraju terapije koje su praćene porastom aktivnosti AAP i GGT, veoma osetljivih indikatora nefrotoksičnosti. Za čitavo vreme sprovođenja terapije nije došlo do porasta aktivnosti lizozomalnog enzima NAG, što znači da ne dolazi do težih oštećenja ćelija epitela proksimalnih tubula na nivou organela.