1b) .@edgarvlermamd will be reviewing the mechanism of action #MOA of #mineralocorticoid receptor antagonists #MRAs in potential #renoprotection for pts with #CKD. He will also address the differences between #steroidal and #nonsteroidal MRA therapies pic.twitter.com/I7y7rcxjm0
— @CKD_ce (@ckd_ce) May 3, 2023
2) Inflammation plays an important role in the pathophysiology of CKD
— @CKD_ce (@ckd_ce) May 3, 2023
Inflammation is a common link between AKI and CKD, and increased expression and/or activation of TLR, NLRP3 inflammasome, and NF-ĸB are present in both scenarios
🔓https://t.co/WPlxwS9FwE pic.twitter.com/tsZXApTdWO
3b) Stimulation of mesangial cells w/aldosterone ➡️ myofibroblastic transdifferentiation assoc'd w/⬆️ collagen gene expression & apoptosis
— @CKD_ce (@ckd_ce) May 3, 2023
Complementary interplay of cascades of injury, inflammation, & fibrosis is initiated & sustained by MR activation
🔓https://t.co/ln14oT8G6b pic.twitter.com/Kmativ0957
5a) Under conditions of ⬆️#aldosterone release or high salt intake, overactivation of the MR is believed to initiate an #inflammatory response that may ultimately lead to end-organ damage pic.twitter.com/ewOndMXjlk
— @CKD_ce (@ckd_ce) May 3, 2023
5c) There are common pathophysiological mechanisms in the heart and the kidneys that show direct deleterious effects of #aldosterone/MR activation
— @CKD_ce (@ckd_ce) May 3, 2023
🔓 https://t.co/Jvb7kT85wR pic.twitter.com/27kdlyL04v
7) Preclinical data ➡️ overactivation of MR in podocytes ➡️⬆️ oxidative stress, ➡️cellular injury & proteinuria.
— @CKD_ce (@ckd_ce) May 3, 2023
Mineralocorticoid receptor antagonists (#MRAs) are pharmacological agents that inhibit interaction btwn the MR & its ligands, eg aldosterone
🔓https://t.co/ln14oT8G6b pic.twitter.com/MSl3hqrKIw
9) There are important differences in pharmacological effects between steroidal and nonsteroidal #MRAs
— @CKD_ce (@ckd_ce) May 3, 2023
🔓 https://t.co/TdYXPS9aUt
👉Selectivity and potency to the MR
👉Organ distribution
👉Half-life
👉Effect on blood pressure (#BP)
👉Equivalent dose pic.twitter.com/NYLNXRlDVS
11a) Use of these #MRAs in treating patients with cardiovascular disease #CVD has been documented in a number of clinical trials, leading to clinical indications for improving survival outcomes in patients with #heart failure #HF with reduced ejection fraction #HFrEF
— @CKD_ce (@ckd_ce) May 3, 2023
12a) Subsequently, it was shown that tx with a more selective steroidal #MRA #eplerenone ⬆️survival & ⬇️rate of hospitalizations for HF #HHF among pts w/ #AMI complicated by #LV dysfunction & #HF and among patients with systolic HF with mild symptoms
— @CKD_ce (@ckd_ce) May 3, 2023
🔓 https://t.co/TO1lhT7TIs pic.twitter.com/eyuu9L81j2
13) Both #spironolactone & #eplerenone appear to have beneficial effects on the kidney
— @CKD_ce (@ckd_ce) May 3, 2023
Meta-analyses ➡️ steroidal #MRAs improved albuminuria across several clinical trials evaluating 24h urinary albumin excretion #UAEhttps://t.co/KK0NtXYXFY
🔓 https://t.co/7JTVfkQIAK pic.twitter.com/nvoohb5OI0
15) Per package inserts, spironolactone is contraindicated in pts w/ #hyperkalemia & is dosed 25mg/day if serum K+ < 5.0 mEq/L. Eplerenone is contraindicated if serum K+ > 5.5 mEq/L at initiation and/or if #CrCl 30mL/min or lowerhttps://t.co/pMiQmzHDaPhttps://t.co/WeJ4tebBNq pic.twitter.com/ZOgV8ZSWVs
— @CKD_ce (@ckd_ce) May 3, 2023
17) ⬆️ risk of hyperkalemia may also limit use of steroidal #MRAs in pts tx'd w/ RAS inhibitor, such as an #ACEi or #ARB, as advanced #CKD, #T2D, #CVD + use of #RASi = documented risk factors of #hyperkalemia
— @CKD_ce (@ckd_ce) May 3, 2023
🔓 https://t.co/1AtGTuI26d pic.twitter.com/6dM14BBOkZ
18b) Data from #AMBER ➡️pts w/resistant #hypertension + stage 3 to 4 #CKD (eGFR of 25 to ≤45) had more prolonged antihypertensive benefit from spironolactone w/ less hyperkalemia if potassium binder #patiromer added to #SOChttps://t.co/8AxNTge4zp
— @CKD_ce (@ckd_ce) May 3, 2023
18d) Increased serum potassium was the most common reason for drug discontinuation in this trial, occurring in more patients treated with placebo (23%) than #patiromer (6.8%) pic.twitter.com/4F7Vx4jJvl
— @CKD_ce (@ckd_ce) May 3, 2023
19b) #FIDELIO_DKD 🔓 https://t.co/hpuUIH51cM#VisualAbstract by @whatstehgfr pic.twitter.com/7ErqpTFS9J
— @CKD_ce (@ckd_ce) May 3, 2023
19d) #FIDELITY 🔓 https://t.co/LOPaHkIV1H pic.twitter.com/9JBTAnkO8b
— @CKD_ce (@ckd_ce) May 3, 2023
19f) #EMPA_KIDNEY
— @CKD_ce (@ckd_ce) May 3, 2023
(earn more credit, learn more at https://t.co/7Q90SSXQ8X)
🔓https://t.co/giaP2yFpxJ pic.twitter.com/4twZmlGVmu
20b) #Aldosteroneand/or #MR overactivation induce all but which of the following?
— @CKD_ce (@ckd_ce) May 3, 2023
a. oxidative stress
b. inflammation
c.⬆️potassium excretion
d. fibrosis
21a) WELCOME BACK! We are talking mechanism of action #MOA of #mineralocorticoid receptor antagonists #MRAs in potential #renoprotection for pts with #CKD. Our returning expert faculty is #nephrologist Edgar V. Lerma 🇵🇭 @edgarvlermamd. pic.twitter.com/59dlvEnzRK
— @CKD_ce (@ckd_ce) May 4, 2023
22) #Nonsteroidal #MRAs are designed to protect the kidney and the heart with a more manageable side-effect profile compared with steroidal MRAs
— @CKD_ce (@ckd_ce) May 4, 2023
– See effects of finerenone and placebo on serum potassium levels in the safety analysis set
🔓 https://t.co/hpuUIH51cM pic.twitter.com/gDZt2hZ7pn
24) Finerenone is indicated in the US (first approval, 2021) to ⬇️ risk of sustained estimated #eGFR decline, #ESKD, #cardiovascular death, nonfatal myocardial infarction, and #HHF in patients with #CKD associated with #T2D
— @CKD_ce (@ckd_ce) May 4, 2023
🔓 https://t.co/ln14oT8G6b pic.twitter.com/y3bgxqJ94a
26) Finerenone significantly ⬇️ #DKD-associated morbidity & mortality v placebo w/o inducing substantial #BP-lowering effects in pts w/stage 2-4 #CKD + #T2D on background of maximally tolerated #RASi#FIDELIO_DKD 🔓 https://t.co/hpuUIH51cM#VisualAbstract by @whatstehgfr pic.twitter.com/0TeUPJl3i5
— @CKD_ce (@ckd_ce) May 4, 2023
27b) . . . and was associated with a higher incidence of urinary #albumin remission in patients with #T2D and high levels of #albuminuriawho were receiving a #RAS inhibitor
— @CKD_ce (@ckd_ce) May 4, 2023
🔓 https://t.co/aKEkEd12Uu pic.twitter.com/4izdswVZrt
29) This diagram shows the beneficial effects of both steroidal and nonsteroidal #MRAs in the #kidney, heart and vasculature in preclinical studies of #DKD from @NatRevNephrolhttps://t.co/t1Nd8LTV1j pic.twitter.com/4cuEjZbrSf
— @CKD_ce (@ckd_ce) May 4, 2023
30b) The answer is b. #Finerenone is NOT an effective #antihypertensive but has salutary impact re the other 3 options. The nonsteroidal #esaxerenone, which is not approved in 🇺🇸, does have antihypertensive efficacy, so this isn't necessarily a class effect of the nonsteroidals.
— @CKD_ce (@ckd_ce) May 4, 2023
31) And that's it! Your just earned 0.75hr 🆓CE/#CME under the tutelage of expert #nephrologist @edgarvlermamd. Claim your credit NOW at https://t.co/XGTAB7TQTS and FOLLOW US for more expert-authored #nephrology #MedEd posted wholly on Twitter! I am @edgarvlermamd–THANK YOU!
— @CKD_ce (@ckd_ce) May 4, 2023