Abstract: In order to study methotrexate nephrotoxicity, the activities of proximal
tubule epithelial cell membrane enzymes: alanine aminopeptidase (AAP) and gammaglutamyltransferase (GGT), as well as of lysosomal N-acetyl-beta-D-glucosaminidase
(NAG) and urinary albumin concentrations 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 AAP and GGT activities, expressed as U/mmol
creatinine was observed after the first two (p < 0.05), as well as after the remaining two
therapies (p < 0.01) in relation to the control. Enzymatic activities of these two enzymes
decreased to control value before the second and the third methotrexate application, but
they increased again after the third application and remained elevated up to the end of experiments. Significant increase of NAG activity expressed as U/mmol creatinine
(p < 0.01), as well as urinary albumin levels (mg/mmol creatinine; p < 0.01) were registered
after the third methotrexate therapy and this elevation of the same statistical significance of
the differences remained stable till the end of the therapy. Based on these results it can be
concluded that during the time period of two first applications nephrotoxic methotrexate action is reversible and at the level of proximal tubule epithelial cell membranes. During the
last two applications impairment is irreversible and at the level of cell organelles and glomerular filtration.
