1b) This is part of a foundational 🫘 #MedEd #accredited series hosted by core @ckd_ce faculty @sophia_kidney. See prior #tweetorials, still available for 🆓CE/#CME credit, at https://t.co/wBHAVb7FEi.
— @CKD_ce (@ckd_ce) October 17, 2023
3) So . . . let's start by getting you to do some lateral thinking!
— @CKD_ce (@ckd_ce) October 17, 2023
Can you connect these 2⃣ graphics? pic.twitter.com/HeswUloqNc
5a)💊#Nirogacestat: a small-molecule inhibitor of the γ-secretase enzyme complex, responsible for the proteolytic cleavage of #NOTCH (Neurogenic locus notch homolog protein receptor), is one treatment option for #desmoid tumors
— @CKD_ce (@ckd_ce) October 17, 2023
6) Here we discuss #nirogacestat & hypophosphatemia, re an observation in @KIReports from @gudnephron @renalmyeloma @kdjhaveri in reference to https://t.co/WiL2uriJub in @NEJM.
— @CKD_ce (@ckd_ce) October 17, 2023
And here is the link to the @KIReports commentary:https://t.co/55SHYUjxn7
8) Results:
— @CKD_ce (@ckd_ce) October 17, 2023
📌Pts receiving nirogacestat had a 71% ⬇️ risk of disease progression or death vs those on placebo
🗓️After 2 years, chances of disease-free progression were 76% on #nirogacestat vs 44% on placebo pic.twitter.com/ndeffIYf5A
10) So, 🤔. . . 📌Was #hypophosphatemia observed in other cancers tx'd with γ-secretase inhibitors? 📌Well, here is a summary of studies published in the @kireports piece 📌Could this mean it is a ‘’class effect’’? What would be the proposed mech?https://t.co/55SHYUjxn7 pic.twitter.com/zIUFco0DrW
— @CKD_ce (@ckd_ce) October 17, 2023
11b) Perhaps it should . . . sodium phosphate transporter-2b is primarily responsible for reabsorption of phosphates in the kidneys . . . so if #nirogacestat has an effect there & induces renal phosphorus wasting . . . pic.twitter.com/gwAiQxKLPy
— @CKD_ce (@ckd_ce) October 17, 2023
12b) Should also check out levels of phosphaturic hormones such as parathyroid hormone #PTH and fibroblast growth factor-23 in pts treated with #nirogacestat. NTK as nirogacestat is becoming #SOC for #desmoid tumors! pic.twitter.com/fvUtJNVq8w
— @CKD_ce (@ckd_ce) October 17, 2023
14a) And a couple ❓s to answer! First, blocking #NOTCH signaling in a pt with a susceptible tumor causes what?
— @CKD_ce (@ckd_ce) October 17, 2023
a. tumor cell apoptosis
b. slower tumor cell growth
c. immune response to tumor
d. all of the above
14c) Turns out #phosphates are rather promiscuous, with levels being directly affected by NaPi-IIb, #calcitonin, FGF-23, #parathyroid hormone, #thyroxine, #ACTH, and others . . . but not a, #aldosterone. Good job!
— @CKD_ce (@ckd_ce) October 17, 2023
15) And with that, you just earned 0.5hr🆓CE/#CME! Claim your certificate NOW at https://t.co/5SxrUAagNo. Thanks for following this 🧵! Get more #MedEd #nephtwitter by FOLLOWING @ckd_ce.
— @CKD_ce (@ckd_ce) October 17, 2023
Thanks to guest faculty @happiedoc !
🙏@Kireports @ISNkidneycare @academiccme @sophia_kidney