Methotrexate Associated Renal Impairment Is Related to Delayed Elimination of High-Dose Methotrexate.

Shi-Long Yang,Hua Song,Di-Ying Shen,Fen-Ying Zhao,Xiao-Jun Xu

doi:10.1155/2015/751703

Shi-Long Yang, Hua Song + Show 3 more

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https://doi.org/10.1155/2015/751703

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Abstract

Although Methotrexate (MTX) is an effective drug for the treatment of acute lymphoblastic leukemia (ALL), the toxicity remains a significant problem. In this prospective study, fifty-four patients with ALL were enrolled. 3 g or 5 g MTX/m2 was administered over 24 hours. Serum MTX concentrations were determined in 24, 48, and 96 hours after MTX infusion. Serum creatinine concentrations and creatinine clearance rate (CCR) were determined before and 24 and 48 hours after MTX infusion. A total of 173 courses of MTX infusion were administered. The serum creatinine concentrations did not change much after MTX infusion while the CCR was gradually decreased. MTX clearance status was independently related to CCR decrease, with the risk of 8.07 to develop renal impairment in patients with delayed MTX elimination. Serum creatinine concentration, serum creatinine ratio, CCR, and CCR ratio at 24 hours were all related to MTX elimination delay. Patients with serum creatinine level >35.0 μmol/L, creatinine ratio >1.129, or CCR <100.0 mL/min were more likely to undergo MTX elimination delay. In conclusion, MTX could induce transient renal impairment and compromised renal function will delay MTX clearance. The serum creatinine concentration and the ratio and CCR are useful tools for evaluating MTX elimination status.

Highlights

Methotrexate (MTX) is one of the essential agents for the extramedullary leukemia prophylaxis in acute lymphoblastic leukemia (ALL), non-Hodgkin’s lymphoma, and osteosarcoma protocols, which has led to significant improvements in the long-term survival of these patients [1,2,3,4,5]
We compared the demographic features and some potential characteristics that may be correlated with MTX elimination, including age, height, weight, body surface area (BSA), serum creatinine level, serum creatinine ratio, urine output, and clearance rate (CCR)
We found that patients with serum creatinine level >35.0 μmol/L, serum creatinine ratio >1.129, CCR level

Summary

Introduction

Methotrexate (MTX) is one of the essential agents for the extramedullary leukemia prophylaxis in acute lymphoblastic leukemia (ALL), non-Hodgkin’s lymphoma, and osteosarcoma protocols, which has led to significant improvements in the long-term survival of these patients [1,2,3,4,5]. Genetic polymorphisms relating to MTX metabolism significantly affect long-term survival of patients with ALL [6, 7]. The toxicity is even severer in patients with elimination delay of MTX [12]. These models were not informative enough for patients with delayed MTX elimination. Serum MTX concentration monitoring is still a standard approach for identifying patients at high risk of developing toxicity. There are still many oncological institutions that cannot carry out serum MTX concentration measurement in China, so it is of great importance to find a simple and convenient way to screen out patients at high risk of developing toxicity

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