Influence of high-dose methotrexate therapy (HD-MTX) on glomerular and tubular kidney function.

摘要: Background The present investigation was intended to further clarify the mechanisms involved in renal dysfunction following high-dose methotrexate (HD-MTX) treatment. Patients and Methods Fifty eight predominately pediatric patients [39 male, 19 female; mean age 12.3 years (range 2.2–34.1)] suffering from acute lymphoblastic leukemia (ALL, n = 28), Non Hodgkins lymphoma (NHL, n = 13), osteosarcoma (n = 8), malignant brain tumor (n = 6), or an ALL relapse (n = 3), were prospectively examined. In course of 220 infusions HD-MTX, glomerular tubular function determined by measuring proteinuria filtration rate (GFR), as well excretion alpha-1-microglobulin (AMG) N-acetyl-β-D-glucosaminidase (NAG). It investigated whether there differences MTX toxicity dependence on administered dose (1, 5, 12 g/m2 BSA), combination with other cytostatic agents (ifosfamide cyclophosphamide), metabolism into 7-OH-MTX, pre-treatment MTX. Results The administration HD-MTX has no direct tubulotoxic effect. The disturbance dependently indicated increase a decrease GFR; all changes completely reversible did not correlate 7-OH-MTX. Increasing number therapeutic cycles nephrotoxicity MTX. Conclusion MTX is directly tubulotoxic. Its side effects glomeruli are usually without clinical relevance. Med Pediatr Oncol 2003;40:348–354. © 2003 Wiley-Liss, Inc.