Effective elimination of high-dose methotrexate by repeated hemodiafiltration and high-flux hemodialysis in patients with acute kidney injury. (March 2022)

• Record Type: Journal Article
• Authors: Sakran, Razan; Milo, Gai; Jabareen, Ali; Artul, Tareq; Haim, Nissim; Litvak, Michael; Ringelstein-Harlev, Shimrit; Horowitz, Nethanel; Efrati, Edna; Assady, Suheir; Kurnik, Daniel
• Is Part Of: Journal of oncology pharmacy practice. Volume 28:Number 2(2022)
• Page Start: 508
• Page End: 515
• Publication Date: 2022-03
• Subjects: High-dose methotrexate -- acute kidney injury -- delayed methotrexate excretion -- high-flux hemodialysis -- online hemodiafiltration; Cancer -- Chemotherapy -- Periodicals; Clinical pharmacology -- Periodicals; 616.994061
• DOI: 10.1177/10781552211052564
• Languages: English
• ISSNs: 1078-1552

Abstract

Introduction: Acute kidney injury (AKI) after high dose methotrexate (HD-MTX) is associated with delayed MTX-excretion and life-threatening toxicity. Glucapridase, the recommended therapy, is expensive and not always available. Case series: We describe 3 cases (69, 67, 73 years) with diffuse large B-cell lymphoma who developed AKI and early-onset severely delayed MTX elimination after HD-MTX. MTX serum concentrations were 101 and 69 μmol/L at 24 h after administration in two patients and 34 μmol/L at 32 h in the third. Management and outcome: Since glucarpidase was unavailable, we performed daily high-flux hemodialysis (HF-HD) or online hemodiafiltration (HDF) sessions (median duration, 6 h). The median serum MTX elimination half-life during HDF/HF-HD sessions was similar in all patients (median, 4.4 h; IQR, 3.8–5.3 h), but serum MTX concentrations rebounded after each dialysis by a median of 40% of the trough concentrations. The three patients underwent multiple dialysis sessions, until MTX serum concentrations remained sufficiently low to be neutralized by leucovorin. Only 1 patient developed severe pancytopenia, and renal function normalized in all patients after 3–6 weeks. Discussion: In conclusion, when glucarpidase is unavailable or delayed, early, repeated and prolonged HDF/HF-HD effectively enhance MTX elimination and prevent toxicity in patients with AKI and severely delayed MTX elimination after HD-MTX.