Renal function as a predicting model for plasma methotrexate concentration after high-dose methotrexate chemotherapy in pediatric malignancy

Abstract

Introduction: Methotrexate (MTX) is the most generally administered antimetabolite in pediatric cancers. Renal excretion is the major route of elimination of MTX. However, renal toxicity and delayed MTX elimination is a particular concern and direct serum MTX concentration is a gold standard for renal toxicity monitoring. However, checking plasma MTX concentrations in most oncology institutions is not always possible especially in less developed countries. Objectives: The purpose of this study was to further assess the renal function after administration of high-dose MTX by parameters such as serum creatinine and Cr clearance rate. Patients and Methods: This is a cross-sectional descriptive analytic study. The study was conducted on children with acute lymphoblastic leukemia, non-Hodgkin lymphoma and osteosarcoma receiving high doses MTX. Patients’ age was ranged from 5 to 16 years. Serum MTX concentration and serum Cr were measured at 24, 48 and 96 hours after receiving MTX and then Cr clearance calculated based on available formulas. All the statistical analyses were done by SPSS 20.0 statistical software Results: This study was performed on 4 patients with osteosarcoma, 3 patients with leukemia and one patient with lymphoma. MTX concentration reduced significantly during 96 hours (P<0.001). A significant correlation between Cr clearance at 48 hours and the average of serum MTX concentration (P=0.001) were observed. Furthermore there were significant correlations between Cr at 24 hours (P=0.003), 48 hours (P=0.009) and 96 hours (P=0.044), with the average of serum MTX concentration. Conclusion: Our findings indicated that serum Cr and Cr clearance can be used to estimate the average of serum MTX concentrations.

Serum Methotrexate Level and Side Effects of High Dose Methotrexate Infusion in Pediatric Patients with Acute Lymphoblastic Leukaemia (ALL)

“…On the second day of discharge, the child was reported with manifestations of other related toxicities like mucositis, neutropenia, leucopenia, thrombocytopenia, anaemia, skin peeling, uremia, and high creatinine. Similar toxicities were reported by Kaveb et al [20]. Serum methotrexate level at the time of readmission (the sixth day of MTX infusion was found to be 0.95 lmol/L).…”

Acute Kidney Injury in Methotrexate treated Leukemia

“…One of the major issues with the treatment of High dose methotrexate is Acute kidney injury. The rise in serum creatinine in relation to the High dose methotrexate infusion has been associatedwith decreased methotrexate clearance in children with Acute Lymphoblastic Leukemia [8]. The identification and incidence of High dose methotrexate-induced renal damage becomes valuable to prevent its toxicity.…”