Urine Methotrexate Concentration at 46-48 Hours Post-Treatment Reflects Methotrexate-Induced Acute Kidney Injury

Early identification of methotrexate-induced acute kidney injury (AKI) and delayed elimination of methotrexate are critical to limiting toxicity of the drug. The current monitoring strategy consists of serial serum methotrexate concentrations at 24, 36, 42, and 48 hours. Appropriate serum concentration monitoring and intervention does not always prevent AKI. Therefore, ongoing study of biomarkers and improved methods of screening for methotrexate-induced AKI is critical to reduce toxicity. This case series reports urine methotrexate values of 4 patients undergoing treatment with high-dose methotrexate. Urine methotrexate concentration was measured 46 to 48 hours after methotrexate infusion. Urine methotrexate concentration was compared with the duration of drug clearance from the serum. Only 1 patient (case 3) developed AKI. Serum concentration of methotrexate were < 0.3 μmol/L at 42, 48, and 48 hours in patients 1, 2, and 4, respectively, and at 168 hours in patient 3 (p < 0.01). Urine methotrexate concentrations were 2.77, 6.45, and 7.8 (μmol/L), in patients 1, 2, and 4, respectively, and 113.69 (μmol/L) in patient 3 (p < 0.001). This case series provides preliminary data that urine methotrexate concentration at hours 46 to 48 may reflect AKI. Future studies should investigate the ability of serial urine methotrexate concentrations to predict delayed drug clearance and the development of AKI.