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  • Title: Influence of high-dose methotrexate therapy (HD-MTX) on glomerular and tubular kidney function.
    Author: Hempel L, Misselwitz J, Fleck C, Kentouche K, Leder C, Appenroth D, Rost M, Zintl F.
    Journal: Med Pediatr Oncol; 2003 Jun; 40(6):348-54. PubMed ID: 12692801.
    Abstract:
    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 the course of 220 infusions of HD-MTX, glomerular and tubular renal function was determined by measuring proteinuria and glomerular filtration rate (GFR), as well as renal excretion of alpha-1-microglobulin (AMG) and N-acetyl-beta-D-glucosaminidase (NAG). It was investigated whether there were differences in MTX toxicity in dependence on the administered dose (1, 5, or 12 g/m(2) BSA), on the combination with other cytostatic agents (ifosfamide or cyclophosphamide), on the metabolism of MTX into 7-OH-MTX, and on pre-treatment with MTX. RESULTS: The administration of HD-MTX has no direct tubulotoxic effect. The disturbance in glomerular function was dose dependently and indicated by an increase in proteinuria as well as by a decrease in GFR; all changes were completely reversible and did not correlate to the metabolism of MTX to 7-OH-MTX. Increasing the number of MTX therapeutic cycles did not increase the nephrotoxicity of MTX. CONCLUSION: MTX is not directly tubulotoxic. Its side effects on glomeruli are usually without clinical relevance.
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