Polyuria associated with high-dose methotrexate in two patients with acute lymphoblastic leukaemia.

Although methotrexate has an established safety profile in clinical practice, severe morbidity can still occur on rare occasions. We report two patients with leukemia treated with high dose methotrexate. Both patients developed profound polyuria that required aggressive fluid resuscitations during the treatments. Renal toxicity is a known complication of methotrexate, but polyuria associated with its use has not been reported before. Polyuria started shortly after the initiation of the medicine in both patients. The polyuria resolved as the drug level in blood became undetectable. The episodes of polyuria were transient and recurred every time when the patients received methotrexate. The clinical pictures were not compatible with classical drug induced nephrogenic diabetes insipidus. It is possible that the drug interferes with adenosine metabolism, which in turn alters the tubular ability of solute and fluid reabsorption.