NEPHROTOXICITY OF LOW-DOSE METHOTREXATE IN GUINEA-PIGS - AN ULTRASTRUCTURAL-STUDY

The nephrotoxicity of low-dose methotrexate (MTX) and the rescue effec t of leucovorin were studied by electron-microscopic examination of th e kidney of guinea pigs. One group received MTX as a single weekly dos e of 10 mg/kg, i.p.; a second group received a similar dose divided in to three equal fractions. The third group received MTX rescued with an equal dose of leucovorin. The distal convoluted tubule showed cell sw elling, fragmentation of the endoplasmic reticulum and loss of mitocho ndrial cristae and matrix. Leucovorin minimized these changes. The pro ximal tubule and the glomerulus were not affected. Low-dose MTX induce d a nephrotoxicity in the distal convoluted tubule which could be mini mized by leucovorin. Mild myelosuppression was also observed.