• Tatjana Vujić Agency for Drugs and Medical Devices of Bosnia and Herzegovina, Veljka Mlađenovića bb, Banja Luka
  • Biljana Davidović Plavšić Banja Luka University, Faculty of Science, Mladena Stojanovića 2, 78000 Banja Luka, Republic of Srpska
  • Snježana Uletilović Banja Luka University, Faculty of Medicine, Save Mrkalja 14, 78000 Banja Luka, Republic of Srpska
  • Svjetlana Stoisavljević Šatara Banja Luka University, Faculty of Medicine, Save Mrkalja 14, 78000 Banja Luka, Republic of Srpska
  • Jelica Predojević Samardžić University-Clinical Center Banja Luka
  • Živko Saničanin Banja Luka University, Faculty of Medicine, Save Mrkalja 14, 78000 Banja Luka, Republic of Srpska



In order study methotrexate nephrotoxicity, the activities of proximal tubule epithelial cell membrane enzymes: alkaline phosphatase (AP) and lactate dehydrogenase (LDH) were determined in 12-h-urine samples of 30 patients with lymphoblastomous leukemia. The patients were i.v. receiving 4 individual methotrexate doses of 2000 mg/m2 every 15 days followed by leucovorin as a protector. Control and methotrexate-treated group, each consisting of 30 examinees, included 4-10 years old children of both sexes.

 Statistically significant increase of AP and LDH activities, expressed as unuts/mmol creatinine was observed after the second therapy (p < 0.05) in relation to the control. Based on these results it can concluded that nephrotoxic methotrexate action is ireversible during the time period after the second applications at the level of proximal tubule epithelal cell


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