The effect of high-dose methotrexate on renal tubules as indicated by urinary lysozyme concentration

Abstract

Lysozyme was measured after 186 doses of methotrexate (MTX) to 88 patients. After 7.5% of the doses, lysozyme rose to between 2 and 19 m̈g/cc and in 3.2% it rose to between 20 and 120 m̈g/cc. These increases had no relationship to the age of the patients, their dose of MTX, the total number of times that MTX had been given, nor to rises in serum creatinine. It did correlate with the administration of aminoglycosides (a part of the supportive care of these patients) in two thirds of these cases. In the patients who did not receive aminoglycosides, no urinary lysozyme concentration rose above 19 m̈g/cc, not even in the patients who became oliguric or required hemoperfusion. Most of these rises occurred early and were of 24 to 48 hour duration. The rises occurring after five days were persistent and were associated with prolonged MTX serum concentrations, suggesting that tubular damage due to MTX was the result of prolonged exposure to MTX, rather than the primary cause of kidney damage, i.e., the event causing the prolonged serum concentrations.

Survival After Unexpected High Serum Methotrexate Concentrations in a Patient with Osteogenic Sarcoma

“…Methotrexate may be a direct tubular toxin (Abelson et al 1983;Condit et al 1969). Against this hypothesis is a study which demonstrated that urinary lysozyme concentrations were not increased in patients with methotrexateinduced renal injury (Freeman-Narrod et al 1982). Abelson et al (1983) demonstrated that nontoxic courses of high dose methotrexate caused a subclinical decrease in glomerular filtration rate with each administration, which could reflect not only a secondary decrease due to tubular dysfunction but also a primary effect in the glomerulus.…”