2) This series is supported by educational grants from AstraZeneca & Bayer, & is intended for healthcare professionals. Accreditation statement & faculty disclosures are at https://t.co/PHlIppl6Yw, and earlier programs, still available for credit, are at https://t.co/8lmzd7ADnj.
— @CKD_ce (@ckd_ce) June 22, 2022
4) … in response to #hyperkalemia or sodium depletion, aldosterone is the culmination of activation of the renin-angiotensin system. It is key to controlling both #bloodpressure and extracellular volume homeostasis by ⬆️ renal sodium reabsorption & ⬆️potassium excretion.
— @CKD_ce (@ckd_ce) June 22, 2022
6) The history of recognizing these diverse impacts is nicely recounted by Epstein in 🔓https://t.co/MKQ4pUAGMC. In its "nonepithelial role", aldosterone in promotes inflammation, collagen formation, fibrosis, and necrosis. Chronically elevated aldosterone, especially …
— @CKD_ce (@ckd_ce) June 22, 2022
8) … might be mediated by MR activity. Similarly, data suggests that blockade of the #MR_receptor might slow progression of #CKD because its activation by #aldosterone promote inflammation and fibrosis and manifests as #proteinuria and #nephrosclerosis.
— @CKD_ce (@ckd_ce) June 22, 2022
10) … mortality and hospitalization when treating #heartfailure. For example, #HFrEF guidelines from @ACCinTouch updated this year state that "aldosterone antagonists are added in as part of the therapy for patients with symptomatic chronic HFrEF who are already receiving …
— @CKD_ce (@ckd_ce) June 22, 2022
12) And also in 2021, new @escardio #HF guidelines state, "MRAs (spironolactone or eplerenone) are recommended, in addition to an ACE-I &a beta-blocker, in all patients with HFrEF to reduce mortality and the risk of hospitalization for HF #HHF. They also improve symptoms.
— @CKD_ce (@ckd_ce) June 22, 2022
14) How does this happen? Again, it's a steroid effect and it's off 🎯when one thinks of #aldosterone simply ⬆️potassium retention. #Spironolactone induces #gynecomastia by decreasing #testosterone production, by …
— @CKD_ce (@ckd_ce) June 22, 2022
16) And aye, there's the rub. The problem with steroidal MRAs? Side-effects! Primary? #hyperkalemia Others? #gynecomastia #erectiledysfunction #menstruation irregularities. BTW, "aye there's the rub" were #Hamlet's words when he discovered #uremic #pericarditis. pic.twitter.com/9rRbPngKca
— @CKD_ce (@ckd_ce) June 22, 2022
18) Return TOMORROW & check ur answer, then buckle up for more learning. @MedTweetorials @goKDIGO @DLBHATTMD @edgarvlermamd @cpcannon @ValleAlfonso @hvanspall @ShelleyZieroth @renaltubules @DrMarthaGulati @JonathanNefro @edurontoFF @GoggleDocs #FOAMed #nephtwitter #cardiotwitter pic.twitter.com/mjKdShHFyh
— @CKD_ce (@ckd_ce) June 22, 2022
20) Yesterday's poll? All but an effect on cardiac conduction. Per @AgarwalRajivMD (🔓https://t.co/9kUKpsuWez), the MR has the same binding affinity for aldosterone and cortisol, & mediates fluid, electrolyte, & hemodynamic homeostasis, as well as tissue repair.
— @CKD_ce (@ckd_ce) June 23, 2022
22) These data still carry into contemporary guidelines as cited above. Limitations were ⬆️rates of breast pain & gynecomastia & risk of #hyperkalemia. In fact, a 2004 pharmacoepidemiological study showed . . .
— @CKD_ce (@ckd_ce) June 23, 2022
24) … sodium and importantly potassium, but has fewer progestational and antiandrogenic adverse effects and therefore less painful breast/#gynecomastia risk. The risk of #hyperkalemia however remains a significant limitation of #MRA use and has been shown to limit . . .
— @CKD_ce (@ckd_ce) June 23, 2022
26) But could there be a way to provide a therapeutic MR blockade without the baggage of a steroid? No off-target antiandrogen effects and maybe less hyperkalemia? Enter the #nonsteroidal MRAs! Recently approved 🇺🇸🇪🇺, #finerenone is a novel, selective, nonsteroidal MRA.
— @CKD_ce (@ckd_ce) June 23, 2022
28) Finerenone blocks the MR as a bulky, passive antagonist, is more selective than spironolactone, & is at least as potent. Again per @AgarwalRajivMD, finerenone's physicochemical properties–lipophilicity & polarity–determine tissue penetration & distribution, allowing …
— @CKD_ce (@ckd_ce) June 23, 2022
30) Other differences include a more balanced kidneys-heart distribution for finerenone, improved #pharmacokinetics that may ⬇️hyperkalemia, and thru various mechanisms finerenone likely offers greater protection from cardiac & renal injury/remodelling & stronger inhibition . . .
— @CKD_ce (@ckd_ce) June 23, 2022
32) Mark your response and return tomorrow for the answer, a wrap-up of this program, and your link to FREE CE/#CME—#physicians #nurses #Pharmacists. Nod to @VietHeartPA @Lross246 @SeguraCardio @nephondemand @DrRaniKhatib @HanCardiomd @SABOURETCardio @ChristosArgyrop
— @CKD_ce (@ckd_ce) June 23, 2022
34) So yesterday we were talking about finerenone, the prototypical nonsteroidal #MRA. The poll? #Finerenone has a short half-life. It inhibits cardiorenal fibrosis and it isn't a great #antihypertensive. There have been lots of new data coming out in 2021-22.
— @CKD_ce (@ckd_ce) June 24, 2022
36) Approval was largely on the basis of FIDELIO-DKD which had 1º renal & 2º CV endpoints. It explored the use of finerenone in people with CKD stage 3 or 4 & severely elevated albuminuria & T2D. pic.twitter.com/kHjZDuvW1l
— @CKD_ce (@ckd_ce) June 24, 2022
38) So, who was studied?
— @CKD_ce (@ckd_ce) June 24, 2022
✅7437 participants T2D & CKD
✅ACR 30-300mg/g (microalbuminuria) & eGFR 25-90ml/min (CKD 2-4)
✅ACE 300-5000 (macroalbuminuria) & eGFR at least 60ml/min (CKD stage 1-2; not extensively studied in the past)
✅ Max tolerated #RAAS inhibitor
40) Individuals like those recruited to FIDELIO-DKD i.e., advanced #CKD, were excluded from FIGARO-DKD Additionally, individuals with symptomatic #HFrEF were also excluded as MRAs are a key pillar of HFrEF management with prognostic & symptomatic benefit. pic.twitter.com/kAryJ5CyJc
— @CKD_ce (@ckd_ce) June 24, 2022
42) The 1º composite endpoint was significantly ⬇️by 13% (ARR 1.8%) mainly driven by a 29% RRR in #HHF. Other components of 1º EP were not significantly reduced. #CV benefits were seen in all categories of #UACR & eGFR. Benefits were also independent of #SGLT2i & #GLP1RA use. pic.twitter.com/rklHV0PHl2
— @CKD_ce (@ckd_ce) June 24, 2022
44) Incidence of #hyperkalemia-related discontinuation was not high, but was ⬆️ with #finerenone (1.2%) compared w/placebo (0.4%). This is less than the expected hyperK+ with steroidal MRAs in a similar population.
— @CKD_ce (@ckd_ce) June 24, 2022
46) FIDELIO-DKD was published in 🔓https://t.co/fZrVUNMEKq. FIDELITY, a pre-specified meta-analysis of individual pt data from FIDELIO-DKD & FIGARO-DKD, was presented at the virtual #ESCCongress2021. Again cited @AgarwalRajivMD discusses FIDELITY here: 🔓https://t.co/gWbRtKXLvh
— @CKD_ce (@ckd_ce) June 24, 2022
48) Such data clearly suggest that a nonsteroidal MRA has benefits, especially in patients with CKD/DKD who might benefit from aldosterone inhibition but are at particularly high risk for #hyperkalemia. Data on combo finerenone and #SGLT2i are eagerly awaited in such pts.
— @CKD_ce (@ckd_ce) June 24, 2022
49) That's it! You made it! Claim your 0.5h CE/#CME at https://t.co/g7RVpBsi20 now, & then FOLLOW US for more #accredited serialized #tweetorials. I am @md_pollack. Also please ✔️out @cardiomet_ce for MORE 🆓CE/#CME!
— @CKD_ce (@ckd_ce) June 24, 2022
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