Can Glucarpidase Help Reverse Methotrexate Kidney Damage?

TOPLINE:

Glucarpidase treatment in patients with methotrexate-associated acute kidney injury is linked to 2.7 times higher odds of kidney recovery and faster recovery time. The enzyme also reduces the risk for grade ≥ 2 neutropenia and transaminitis by half vs no glucarpidase treatment.

METHODOLOGY:

• Researchers conducted a multicenter cohort study involving 708 adults with methotrexate-associated acute kidney injury from 28 cancer centers across the United States.
• Analysis utilized a sequential target trial emulation framework to compare outcomes between 209 patients who received glucarpidase within 4 days of methotrexate initiation and 499 patients who did not.
• The primary endpoint was kidney recovery at hospital discharge, defined as survival with serum creatinine
• Secondary endpoints included time-to-kidney recovery, neutropenia and transaminitis on day 7, and time-to-death.

TAKEAWAY:

• Glucarpidase administration was associated with adjusted odds ratio [aOR] of 2.70 (95% CI, 1.69-4.31) and adjusted hazard ratio [aHR] of 1.88 (95% CI, 1.18-3.33) for time-to-kidney recovery.
• Treatment with glucarpidase reduced the risk for grade ≥ 2 neutropenia (aOR, 0.50; 95% CI, 0.28-0.91) and grade ≥ 2 transaminitis (aOR, 0.31; 95% CI, 0.13-0.77) on day 7.
• Female patients showed greater benefit from glucarpidase treatment than male patients (P = .02 for interaction).
• No significant difference was observed in time-to-death between glucarpidase-treated and glucarpidase-untreated patients (aHR, 0.76; 95% CI, 0.49-1.18).

IN PRACTICE:

“These data suggest glucarpidase may improve both renal and extrarenal outcomes in patients with MTX-AKI [methotrexate-acute kidney injury],” the authors of the study wrote.

SOURCE:

This study was led by Shruti Gupta, MD, MPH, and David E. Leaf, MD, MMSc, Brigham and Women’s Hospital in Boston. It was published online in Blood.

LIMITATIONS:

According to the authors, residual confounding cannot be excluded despite adjustment for multiple variables. While glucarpidase-treated patients had similar distributions of most baseline characteristics, they showed greater severity of illness, including more comorbidities, concomitant nephrotoxic medications, higher 24-hour methotrexate levels, and more severe acute kidney injury. This study was limited to patients treated at large, US-based academic centers, potentially affecting generalizability to smaller hospitals or countries where glucarpidase is unavailable.

DISCLOSURES:

This study was funded by BTG International. Gupta disclosed ties with BTG International, Dana-Farber Cancer Institute’s Wong Foundation, Janssen, AstraZeneca, and the National Institute of Diabetes and Digestive and Kidney Diseases (K23DK125672). Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.