A recent study led by Dr. Shruti Gupta and Dr. David E. Leaf from Brigham and Women's Hospital in Boston highlights promising developments for patients suffering from methotrexate-associated acute kidney injury (MTX-AKI). Funded by BTG International, the research involved 708 adult patients from 28 cancer centers across the United States. The study suggests that glucarpidase treatment significantly improves kidney recovery outcomes for these patients, with findings indicating a 2.7-fold increase in the odds of recovery.
The study's primary objective was to determine kidney recovery at hospital discharge, defined by survival with serum creatinine levels less than 1.5 times the baseline without the need for dialysis. Researchers deployed a sequential target trial emulation framework to compare 209 patients who received glucarpidase within four days of methotrexate initiation against 499 patients who did not receive the treatment. Despite similar baseline characteristics, glucarpidase-treated patients exhibited a greater severity of illness, with more comorbidities and severe kidney injury.
Crucially, the analysis revealed that glucarpidase-treated patients showed faster recovery times. The treatment also reduced the risk of grade ≥ 2 neutropenia and transaminitis by day 7. Female patients appeared to benefit more from glucarpidase treatment compared to male patients, with a significant interaction observed (P = .02). However, no significant difference in time-to-death was noted between the treated and untreated groups.
“These data suggest glucarpidase may improve both renal and extrarenal outcomes in patients with MTX-AKI,”
- Shruti Gupta, MD, MPH, and David E. Leaf, MD, MMSc, Brigham and Women’s Hospital in Boston.
The study's secondary endpoints included time-to-kidney recovery, neutropenia and transaminitis on day 7, and time-to-death. Results indicated an adjusted odds ratio (aOR) of 2.70 for kidney recovery and an adjusted hazard ratio (aHR) of 1.88 for time-to-recovery among those treated with glucarpidase.
However, the study's focus on large academic centers in the U.S. may limit its generalizability to smaller hospitals or regions where glucarpidase is unavailable. Despite this limitation, the findings provide a compelling case for further exploration into glucarpidase's role in treating MTX-AKI.
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