Citations 2
Glucarpidase for treatment of high-dose methotrexate toxicity
Gupta, Shruti , Kaunfer, Sarah Allison , Chen, Kevin L. , Dias, Julie‐Alexia , Rajasekaran, Arun , Prosek, Jason, Truong, Huong L. , Wood, Anthony C., Bassil, Claude , Renaghan, Amanda D., Carlos, Christopher A., Kelly, Katherine J. , Passero, Christopher J., Abudayyeh, Ala , Shin, Daniel Sanghoon , Yelvington, Bradley, Kanduri, Swetha Rani , Neyra, Javier A. , Shirali, Anushree C. , Bansal, Anip, Geara, Abdallah Sassine , Mithani, Zain, Ziolkowski, Susan , Rashidi, Arash, Jakubowski, Jonathan, Pujari, Ashwini, Dotson, Emily, Wall, Sarah , Patton, John T. , Barreto, Jason N. , Sheikh, M. Salman , Lee, Jamie, Lucchesi, Nicholas, Kolman, Michael David, Rasheed, Muhammad Ahsan, Afzal, Afsheen, Mahesh, Amrita, Hsu, Raymond K. , Nicolaysen, Anthony, Tefera, Kibrewessen, Schretlen, Claire F. , Miller, Ryan M. , Velez, Juan Carlos Q. , Chandrasekhara, Soniya, Donley, Vicki, Patel, Ashka , Krishnamurthy, Shobana, Ali, Rafia, Yilmam, Osman A , Wells, Sophia L., Ortega, Jessica L. , Green‐Lingren, Olivia, Leaf, Rebecca Karp , Sise, Meghan E. , Nayak, Lakshmi , LaCasce, Ann S. , Leaf, David E. , Kaunfer, Sarah A , Rajasekaran, Arun , Shah, Chintan V , Glezerman, Ilya G , Kelly, Katherine , Abudayyeh, Ala , Neyra, Javier A , Edmonston, Daniel , Ziolkowski, Susan L , Bond, David A , Patton, John , Barreto, Jason N , Herrmann, Sandra M , Sheikh, Mohammad S , Hsu, Raymond K , Aklilu, Abinet M , Krishnamurthy, Shobana , Yilmam, Osman A , Ortega, Jessica L , LaCasce, Ann Steward , Leung, Nelson , Leaf, David E , Gupta, Shruti , Dias, Julie-Alexia , Vijayan, Anitha , Zhang, Jingjing , Drappatz, Jan , Sperati, Christopher John , Rashidi, Arash , Bond, David A. , Patton, John T. , Herrmann, Sandra M. , Baz, Rachid , Lee, Jamie, Kolman, M F , Afzal, Afsheen, Kang, Dasol, Mahesh, Amrita, Miller, Ryan M., Flannery, Alexander H , Aklilu, Abinet M. , Anand, Shuchi , Ni, Jian, Wells, Sophia L., Leung, Nelson
Blood | January 6, 2025 | Volume: 145 | Issue: 17 | Pages: 1858-1869
Abstract High-dose methotrexate (MTX) results in high rates of acute kidney injury (AKI), neutropenia, and hepatotoxicity. Glucarpidase is a recombinant enzyme that cleaves MTX, but clinical data supporting its use are scarce. We examined the association between glucarpidase administration and outcomes in adults with MTX-AKI from 28 cancer centers across the United States using a sequential target trial emulation framework. The primary end point was kidney recovery at hospital discharge, defined as survival to discharge with serum creatinine <1.5-fold baseline and without dialysis dependence. Key secondary end points were time to kidney recovery, neutropenia, and transaminitis on day 7, and time to death. Using multivariable logistic and Cox regression models, we compared outcomes in patients who received glucarpidase within 4 days following MTX initiation with those in patients who did not. Among 708 patients with MTX-AKI, 209 (29.5%) received glucarpidase. Overall, 183 (25.8%) had a primary end point event. Glucarpidase receipt was associated with a 2.70-fold higher adjusted odds of kidney recovery (95% confidence interval [CI], 1.69–4.31) compared with no glucarpidase receipt. Patients treated with glucarpidase also had faster time to kidney recovery (adjusted hazard ratio [aHR], 1.88; 95% CI, 1.18–3.33) and lower risks of grade ≥2 neutropenia (adjusted odds ratio [aOR], 0.50; 95% CI, 0.28–0.91) and grade ≥2 transaminitis (aOR, 0.50; 95% CI, 0.28–0.91) on day 7. There was no difference in time to death (aHR, 0.76; 95% CI, 0.49–1.18). These data suggest glucarpidase may improve both renal and extrarenal outcomes in patients with MTX-AKI.
Medication Management in the Critically Ill Patient with Acute Kidney Injury
Frazee, Erin N. , Flannery, Alexander H , Frazee, Erin N , Behal, Michael L.
Clinical Journal of the American Society of Nephrology | February 1, 2023 | Volume: 18 | Issue: 8 | Pages: 1080-1088
Abstract AKI occurs frequently in critically ill patients. Patients with AKI, including those who require KRT, experience multiple pharmacokinetic and pharmacodynamic perturbations that dynamically influence medication effectiveness and safety. Patients with AKI may experience both subtherapeutic drug concentrations, which lead to ineffective therapy, and supratherapeutic drug concentrations, which increase the risk for toxicity. In critically ill patients with AKI not requiring KRT, conventional GFR estimation equations, especially those based on serum creatinine, have several limitations that can limit the accuracy when used for medication dosing. Alternative methods to estimate kidney function may be informative, including use of measured urinary creatinine clearance, kinetic eGFR, and equations that integrate novel kidney biomarkers. For critically ill patients with AKI requiring KRT, physicochemical properties of the drug, the KRT prescription and circuit configuration, and patient-specific factors each contribute to medication clearance. Evidence-based guidance for medication dosing during AKI requiring KRT is often limited. A working knowledge of the basic tenets of drug elimination during KRT can provide a framework for how to approach decision making when the literature is lacking. Iterative re-evaluation of a patient's progress toward therapeutic goals with a medication must occur over the arc of critical illness, including and especially in the setting of dynamic kidney function.