Difficulty Measuring Methotrexate in a Patient with High-Dose Methotrexate-Induced Nephrotoxicity

This is the authors' abstract. We don't add key points for this paper.

An 18-year-old male presented with pain and swell-ing in his left leg that he noted after playing football. An x-ray of the affected leg showed a destructive lesion that prompted a concern for malignancy. Sub-sequent tests, including magnetic resonance imag-ing, a bone scan, and a needle biopsy of the lesion, confirmed nonmetastatic osteosarcoma in the left proximal tibia. The patient was started on a standard regimen of chemotherapy. He received 4 cycles of high-dose methotrexate (HDMTX)3 with leucov-orin rescue and 2 cycles of cisplatin and doxorubi-cin, which he tolerated well. Each HDMTX course involved the intravenous administration of 20 g methotrexate (MTX) over 4 h. The patient experi-enced delayed MTX clearance after the first cycle but showed typical clearance after the subsequent 3 cy-cles. He then underwent a planned radical resection of the tumor with allograft placement. After the pa-tient recovered from surgery, chemotherapy re-sumed, and the patient received 2 additional cycles of cisplatin and doxorubicin and 1 additional cycle of HDMTX. His treatment was interrupted when he had to undergo surgery for a wound infection in the affected leg. After recovery from the second surgery, the patient received a sixth HDMTX cycle. After this cycle, the patient developed acute nephrotoxicity, which was manifested by marked renal dysfunction and delayed MTX clearance. His plasma creatinine concentration increased from 0.8 mg/dL (8 mg/L) at the start of the cycle to 6.8 mg/dL (68 mg/L) after he received HDMTX. Plasma MTX concentrations