Thread by @kdjhaveri

Tweetorial on MTX related renal toxicity @onconephsociety @ASCO @ASH_hematology @BloodCancerJnl -- See below to start!

1) 🧵/ How do you treat high-dose methotrexate-associated acute kidney injury (MTX-AKI)?

2)A new paper in @BloodJournal led by @ShrutiGkidney ,@SarahKaunfer, @DavidLeaf9 demonstrates the clinical benefit of #glucarpidase
ashpublications.org/blood/article-…

3)/ High-dose methotrexate (HDMTX) is used as a frontline chemotherapy to treat #leukemia and #lymphoma involving the CNS but can cause significant toxicities: #AKI #hepatotoxicity and #neutropenia

4) Glucarpidase is a recombinant bacterial enzyme that cleaves 99% of circulating MTX within 15 minutes of its administration! In 2012, the FDA approved glucarpidase as an antidote for HDMTX toxicity, but this was based on biochemical data alone (i.e., no data on clinical efficacy). 🧪pmc.ncbi.nlm.nih.gov/articles/PMC57…

5)Since no study has rigorously investigated whether glucarpidase actually benefits patients in terms of clinical outcomes, there is wide interhospital variation in its use. Further, guidelines in which patients should receive it are vague and sometimes contradictory.

6)🧵 In this study, investigators across 28 major US cancer centers reviewed the charts of 708 adults with MTX-AKI to determine if glucarpidase receipt improves clinical outcomes. 209 patients received glucarpidase and 499 did not (these patients served as controls).

7) The investigators used a rigorous target trial emulation framework to infer a causal relationship between glucarpidase receipt and kidney recovery. #TargetTrialEmulation jamanetwork.com/journals/jama/…

8) #Glucarpidase receipt was associated with a 2.7-fold higher odds of kidney recovery at hospital discharge compared to no glucarpidase receipt. Results were consistent across multiple sensitivity analyses

9) Glucarpidase receipt was also associated with a faster time-to-kidney recovery- fascinating!

10) #Glucarpidase was also associated with a lower risk of neutropenia and liver toxicity on day 7 post-MTX compared to no glucarpidase.

11)This work contributes importantly to the growing field of onconephrology, and demonstrates the power of multicenter collaboration. In 2021, we helped form the @onconephsociety , pushing the envelope further in this critical area. 🌐 ason-online.org

12)In summary, the findings from this study represent the strongest data to date supporting clinical benefit from glucarpidase for patients with MTX-AKI. @BloodCancerJnl @ASCO @ASH_hematology @ASNKidney @nkf @adqi_p

13)Congratulations to everyone involved in this herculean study, including @ShrutiGKidney, @SarahKaunfer, @DavidLeaf9, @DrLaCasce, @ab2814, @DanEdmonston, @JohnSperati, @HerrmannMD, @MegSise, @claudebassil , @IlyaGlezerman, @SwethaKanduriMD, @JasonProsek (continued ↓)

14) @drappatz , @ZiolkowskiSusan, @Javo_Neyra, @NephronPower, @ChrisCarlos, @ArashRashidi14, @BradleyHemOncRx, @arenaghan1, @VijayanMD, @AnushreeShirali, and @Nephronette
#TweetorialWrapUp @threadreaderapp
#unroll