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

Abstract

Kratak sadr`aj: Radi odre|ivanja nefrotoksi~nosti cefalosporinskog antibiotika cefaleksina, pra}ena je aktivnost enzi ma dominantno lokalizovanih u }elijama epitela proksimalnih tubula, alaninaminopeptidaze (AAP), gama-glutamil-transferaze (GGT) i N-acetil-beta-D-glukozaminidaze (NAG). Odre|ivanje aktivnosti enzima je vr{eno u uzorcima 12-~asovnog 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 sprovo|enja terapije do 15 dana. Aktivnosti istih enzima su odre|ivane i u 12-~asovnom urinu 30 ispitanika kontrolne grupe. I eksperimentalna i kontrolna grupa sastojale su se od ispitanika oba pola, starosti od 3 do 10 godina. Statisti~ki zna~ajne razlike u aktivnostima AAP i GGT, izra`ene u U/mmol kreatinina, registrovane su izme |u ispitanika eksperimentalne i ispitanika kontrolne grupe nakon dvanaestog dana sprovo|enja terapije (p < 0,01). Aktiv nost NAG ispitanika eksperimentalne grupe u odnosu na ispitanike kontrolne grupe se nisu zna~ajno menjale zã itavo vreme petnaestodnevne terapije. Mo`e da se za klju~i da petnaestodnevni tretman ispitanika staro sti od 3 do 10 godina preporu~enim dozama cefa leksina izaziva blage nefrotoksi~ne promene pri kraju terapije koje su pra}ene porastom aktivnosti AAP i GGT, veoma osetlji vih indikatora nefrotoksi~nosti. Za ~itavo vreme sprovo|e nja terapije nije do{lo do porasta aktivnosti lizozomalnog enzim a NAG, {to zna~i da ne dolazi do te`ih o{te}enja }elija epitela proksimalnih tubula na nivou organela. The same enzymes were determined in the 12-h urine samples of the corresponding control. Both the control and the expe ri mental group consisted of 30 examinees of both sexes, age range 3-10 years. Sta tistically 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 incre ased activities of AAP and GGT, the enzymes known as very sen sitive indicators of nephrotoxicity. The results showing that during the entire period of cephalexin appli cation 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.

Activities of Proximal Tubule Enzymes and Albumin Concentration in Urine of Children Treated With Methotrexate

“…A similar trend was also observed after the second methotrexate treatment, i. e. after an initial increase in AAP and GGT activities registered 24 h upon the therapy, the activities of these two enzymes declined to control values before the third methotrexate application. These results are in accordance with our previous findings demonstrating that AAP and GGT represent early, reliable and very sensitive markers of reversible changes in epithelial cell membranes of proximal Page 77 of 79 tubules [23]. The activities of AAP and GGT also significantly increased upon the third methotrexate treatment to remain elevated till the end of the experimental period.…”