Acute kidney injury after high-dose methotrexate application - case report

Area of Science:

• Oncology
• Nephrology
• Pharmacology

Background:

• High-dose methotrexate (HDMTX) is crucial for treating childhood cancers like osteosarcoma.
• Nephrotoxicity is a significant complication of HDMTX, occurring in 1.8%–36% of cases.
• Current management includes hydration, urine alkalinization, and antidote therapy, but renal injury still occurs.

Purpose of the Study:

• To investigate the safety and feasibility of re-administering HDMTX after acute kidney injury (AKI).
• To evaluate the long-term renal prognosis and risk factors associated with HDMTX-induced nephrotoxicity.
• To present a clinical case of successful HDMTX re-challenge in a pediatric osteosarcoma patient.

Main Methods:

• Case report of a 13-year-old female with osteosarcoma who developed grade 4 AKI after HDMTX.
• Renal replacement therapy was initiated due to severe nephrotoxicity.
• Subsequent HDMTX courses were administered with gradually increasing doses (up to 20g) after recovery.

Main Results:

• The patient experienced severe AKI requiring renal replacement therapy after initial HDMTX.
• Four subsequent HDMTX courses were administered at escalated doses (3g/m², 8g/m², 12g/m², up to 20g total).
• All re-challenge courses were well-tolerated with timely drug elimination and no evidence of recurrent nephrotoxicity.

Conclusions:

• Re-administration of HDMTX after AKI is feasible and safe in pediatric osteosarcoma patients.
• Careful monitoring and dose escalation can allow for continued effective cancer treatment.
• This approach may be a viable option when HDMTX is critical for treatment success.