The administration of methotrexate is followed by functional and morphologic changes in the kidney presumably due to direct toxic effects of the drug. Changes in BUN occur that correlate with clinical and hematologic toxicity, the BUN rising as the other symptoms progress. In those patients who recover, the BUN returns to normal as the leukocyte count increases and as the clinical symptoms of toxicity subside. In patients who develop severe toxicity, or in some patients with only moderate toxicity, decreases in the renal clearance of both inulin and PAH can occur. This is usually, though not necessarily, directly related to the dose employed. In addition to these functional changes, histologic examination of the kidneys of several patients who died of methotrexate toxicity showed extensive necrosis of the epithelium of the convoluted tubules.

No abstract

No abstract