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

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.

• Authors: Lutz Hempel, Joachim Misselwitz, Christian Fleck, Karim Kentouche, Christiane Leder, Dorothea Appenroth, Michael Rost, Felix Zintl
• Journal: Medical and pediatric oncology (Med Pediatr Oncol) Vol. 40 Issue 6 Pg. 348-54 (Jun 2003) ISSN: 0098-1532 [Print] United States
• PMID: 12692801 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2003 Wiley-Liss, Inc.

Chemical References

• Antimetabolites, Antineoplastic
• Methotrexate

Topics

• Adolescent
• Adult
• Antimetabolites, Antineoplastic (administration & dosage, adverse effects, therapeutic use)
• Child
• Child, Preschool
• Female
• Glomerular Filtration Rate (drug effects)
• Humans
• Infusions, Intravenous
• Kidney Diseases (chemically induced, physiopathology)
• Kidney Tubules (drug effects, pathology, physiology)
• Male
• Methotrexate (administration & dosage, adverse effects, therapeutic use)
• Prospective Studies
• Proteinuria (etiology)