A recent study from Mass General Brigham indicates that glucarpidase, an FDA-approved medication, may significantly improve kidney recovery in patients experiencing toxicity from the chemotherapy drug methotrexate (MTX). The study, published in Blood, analyzed data from 28 major U.S. cancer centers and found a strong association between glucarpidase treatment and improved outcomes in patients with MTX-induced acute kidney injury (AKI).
Glucarpidase's Impact on Kidney Recovery
The research team, led by Dr. Shruti Gupta from Brigham and Women's Hospital and Dana-Farber Cancer Institute, utilized data from 708 patients with methotrexate-induced AKI between 2000 and 2022. Of these, 209 received glucarpidase within four days of MTX exposure, while 499 did not. The study employed a "target trial emulation" approach to mimic a randomized clinical trial, allowing for causal inferences from real-world data.
The results showed that patients treated with glucarpidase had a 2.7-fold increased likelihood of kidney recovery compared to those who did not receive the drug. Furthermore, the glucarpidase group experienced faster kidney recovery and a lower incidence of severe neutropenia and liver toxicity.
Methotrexate and Kidney Toxicity
Methotrexate is a widely used chemotherapeutic agent, particularly for cancers involving the central nervous system, due to its ability to cross the blood-brain barrier. However, high doses (≥ 500 g/m2) can lead to severe complications, including AKI, liver toxicity, and neutropenia. Glucarpidase works by rapidly converting MTX into inactive metabolites, clearing it from the blood within 15 minutes of administration.
Addressing the Evidence Gap
Despite its FDA approval in 2012, the clinical benefits of glucarpidase have not been comprehensively assessed, leading to variations in its use. This study aimed to address this evidence gap by providing a robust analysis of its potential clinical advantages.
Dr. David E. Leaf, Director of Clinical and Translational Research in Acute Kidney Injury at Brigham and Women’s Hospital, emphasized the importance of these findings: "Our findings offer clinicians evidence-based data supporting glucarpidase." He also noted that, "FDA approval is only the first step. If [patients] aren’t using the drug, then [they] aren’t benefiting from it."
Study Methodology
The researchers meticulously extracted granular data from medical records across the 28 participating cancer centers. This manual chart review allowed them to account for key variables and increase confidence in their findings. Kidney recovery was assessed based on changes in serum creatinine levels at hospital discharge.
Implications for Clinical Practice
The study authors hope that these findings will encourage physicians to consider glucarpidase for patients experiencing kidney toxicity from methotrexate. By providing evidence-based data, this research supports the broader adoption of glucarpidase to improve patient outcomes and reduce the severity of adverse events associated with high-dose methotrexate chemotherapy.
