Thread by @ckd_ce

1) Welcome to our new #accredited #tweetorial which is Part 1 of a 2-part "highlights" program on new #SGLT2i & #DKD data presented at @ERAkidney #ERA22. #Physicians #nurses #pharmacists #PAs and #NPs can all earn 0.5h CE/#CME by following this thread!

2) @ERAkidney #ERA22 is a primary international scientific symposium for interaction and exchange among basic scientists and clinicians working in #Nephrology. It was held in May. Our expert author is Dr. Sheila Bermejo (@shbermejo) from @vallhebron in Barcelona, Spain.

3) This program is #accredited for CE/#CME & is supported by an independent educational grant from the Boehringer Ingelheim/Lilly Alliance. It is not intended for US- or UK-based based HCPs. Accreditation statement & faculty disclosures at ckd-ce.com/disclosures/.

4) So let's start with a quick knowledge ✔️. What is the recommended first line drug therapy for #diabetes_mellitus and chronic kidney disease (#CKD)?
a. #Metformin
b. Metformin + #RAASB
c. Metformin + #SGLT2i
d. Metformin + SGLT2i + RAASB

5) Yes! It's all 3 (D). All 3 #SGLT2i have been demonstrated to improve kidney outcomes, as explained by Dr. Daniël van Raalte in his talk on the first day of the #ERA22 congress entitled “SGLT2 inhibitors: from bench to bedside for patients with cardiorenal síndrome”.

6) This is regardless of whether patients do or do not have #diabetes, according to the results of the #DAPA-CKD clinical trial (🔓pubmed.ncbi.nlm.nih.gov/32970396/)

7) As we all know, an increase in #glomerular pressure that leads to an increase in glomerular filtration rate #GFR occurs in the early stages of diabetic kidney disease #DKD

8a) Patients with #diabetes experience an ⬆️in the reabsorption of glucose & sodium by the SGLT2 channels located in the renal tubule. This causes a ⬇️in the arrival of sodium concentration at the macula densa, which is interpreted as low renal plasmatic flux.

8b) Consequently a dilation of the afferent arteriole occurs, producing an increase in #GFR, known as glomerular #hyperfiltration in the initial stages of evolution of diabetes mellitus.

9) If #SGLT2 blockade occurs, natriuresis increases, bringing a higher concentration of sodium to the macula densa ➡️producing a vasoconstriction of the afferent arteriole and subsequently a restoration of the #GFR, as you can see here

10) Thus, a decrease in renal vascular resistance has been demonstrated with the use of #SGLT2i

11) In addition, a few studies have evidenced hemoconcentration in patients treated with #SGLT2i. One plausible hypothesis is that the increase in intratubular volume that occurs in the macula densa ➡️ hypoxia and a subsequent increase in #EPO production.

12) In pts with #T2D & normal kidney function, the use of #SGLT2i has evidenced an ⬆️in urinary glucose excretion & urinary volume; however, no significant increase in natriuresis was observed. Thus, natriuresis is not a key factor in the benefit of the use of SGLT2i.

13a) In summary, there are numerous pathways through which #SGLT2i are involved with potential #cardiovascular benefit, although they are poorly understood:
👉modulation of CV risk factors
👉hemoconcentration
👉⬆️ oxygen carrying capacity
👉altered cardiac substrate metabolism

13b)
👉⬇️sympathetic nervous system activity
👉direct vascular effect on endothelial function & vascular stiffness
👉induction of a metabolic rest state
👉#aestivation-like response
👉⬇️inflammation
👉⬇️epicardial adipocytokines
👉⬇️cardiac fibrosis

13c)
👉alteration in intracellular sodium stores
👉⬇️uric acid
👉#RAAS modulation
Is there any doubt why "flozinating" has become so popular?!?

14) Taking all of this together, the renal benefits to patients with #T2D of the use of SGLT2i are obvious. Thus, @goKDIGO, @AmDiabetesAssn and @escardio @escardionews guidelines recommend its use as follows, as per a talk at #ERA22 conducted by Dr. Paola Fioretto.

15) In European guidelines @goKDIGO, the use of #SGLT2i is already first-line drug therapy in #T2D.

16) In addition, in the new revision of guidelines, level of #GFR has been lowered to 20 ml/min according to #EMPEROR, #DAPA_CKD, & #CREDENCE trials for the use of #SGLT2i.

17) And we must to take into account the upcoming #EMPA_KIDNEY trial results because this study enrolled a #CKD population with a broad range of #eGFR , with and without albuminuria. We are waiting for these results!!

18a) Questions remain & some clinical situations are unresolved, as Dr. Fioretto pointed out in her #ERA22 talk entitled: “New kidney protective drugs: how do they impact the guidelines?” These include

18b)
1⃣Management of patients with #DKD & normoalbuminuria
2⃣ #SGLT2i in kidney transplant patients
3⃣Management of patients with DKD and #T1D
⌛️Time will tell . . .

19) So what have we learned?
Which of these effects, originally thought to help explain the #CV and #cardiorenal benefits of #SGLT2i, has data shown actually to be NOT so important?
a.⬆️urinary glucose excretion
b.⬆️urinary volume
c.⬆️natriuresis
d.⬇️renal vascular resistance

20) Mark your best response and RETURN TOMORROW for the correct answer and more #ERA22 data on #SGLT2i and #DKD, along with a link to your 🆓CE/#CME.
👏@ClaraGCarro @PepaSolerR @SENefrologia @JonathanNefro @nefrocat @jlgorriz @EdoardoMelilli @SVNefro @CKJsocial @torra_roser

21) WELCOME BACK! I am @shbermejo and we are discussing fascinating data out of May's @ERAkidney #ERA22 congress while YOU earn 🆓CE/#CME for following this 🧵.
👍@ERAkidney @EmiliSanAlv @NefroClassMx @P_Rossing @edgarvlermamd #FOAMed #nephtwitter #cardiotwitter @MedTweetorials

22) Yesterday's quiz (tweet 19)? The correct answer is C. As per tweet 12 ⤴️, natriuresis probably isn't as critical to the mechanism of action of #SGLT2i's benefits on #cardiovascular & #cardiorenal outcomes as once thought.

23a) And now we turn our attention to the #ERA22 mini-oral presentations and other presentations given at the meeting on Friday. The program book for #ERA22 can be downloaded at 🔓academic.oup.com/ndt/issue/37/S…

23b) We are going to highlight here the most interesting new evidence on #SGLT2i provided at #ERA22 in different scenarios, starting with the use of SGLT2i in #CKD patients with and without #diabetes_mellitus.

24) Dr. Afrooghe (MO 157) and colleagues demonstrated a significant ⬇️ in proteinuria with the use of #SGLT2i as well as ⬇️#bloodpressure in a cohort of 30 non-diabetic proteinuric #CKD patients.

25a) Dr. Jelakovic (MO411) in a cohort of patients with and without #DM (n=49) evidenced that the use of #SGLT2i was associated with a ⬇️in BP, as well as proteinuria (NS), a slight ⬆️ in creatinine & an improvement of glycemic control.

25b) It should be noted that the follow-up period was short (4 months), so it was difficult to interpret the evolution of renal function.

26) Now to #HF… Dr. Abdullaev (MO634) in a multicenter study (n=225) with patients with #HFrEF & #HFpEF were randomized to the use of #dapagliflozin vs. placebo. After 1yr of follow-up, risk of worsening HF or CV death was lower in the group treated with dapagliflozin.

27a) Any updates at #ERA22 on the adverse effects associated with the use of #SGLT2i? Yes!
Dr. Marques @mmvidas (MO 167) and colleagues, studied a cohort of 153 patients with #diabetes under treatment with SGLT2i.

27b) Of these, 21.6% were older than 75 years. But the news is reassuring! The use of #SGLT2i in this group of patients were safe: there was no evidence of a higher incidence of side effects.

27c) What about genital infections? Dr. Satta (MO636) and colleagues analyzed a cohort of post-menopausal patients. They compared patients under #SGLT2i treatment vs group control. All of them received strict hygiene-based prevention practices (#SHBPPs) education.

27d) In the treatment group, women non-adherent to SHBPP had a higher % of UTIs than adherent women. In the control group, adherent & non-adherent, UTIs had similar %.

27e) Thus, in postmenopausal patients who start #SGLT2i, it is very important that they receive education properly and we must to check the adherence.

28a) #ERA22 also featured updates on the the basic science of #SGLT2i.
Dr. Vergara @AnderVerg (FC121) and colleagues compared the use of triple therapy with #SGLT2 + #ERA + #ramipril vs Ramipril alone in mice.

28b) Triple therapy was superior vs monotherapy in ⬇️ #BP, lower hyperfiltration, & improved echocardiographic parameters. Also saw a reduction in the expansion of the mesangial matrix & less hypertrophy of #LV cardiomyocytes & collagen deposition.

29a) Further, Dr. Navarro (MO 640) & colleagues showed in a cohort of patients with #diabetes (n=57) that the use of #SGLT2i in 45 (vs 12 with #DPP4i) ➡️⬆️increase in urinary levels of #KLOTHO (an anti-aging single-pass membrane protein predominantly produced in the kidney) . . .

29b) . . . along with a ⬇️in albuminuria & #TNF_alpha. All of this indicates that the use of #SGLT2i improves inflammation and the preservation of #KLOTHO is an important mechanism of renal protection.

30) In summary, multiple presentations at #ERA22 supported the conviction that use of #SGLT2i has a promising present and future, with increasing evidence in favor of its use in the daily clinical practice in patients with and without #diabetes and #CKD.

31) And that's it! Now go and claim your 🆓CE/#CME at ckd-ce.com/dkd12_ERA22a/ and FOLLOW US for more #accredited #tweetorials in the #cardiorenal & #cardiometabolic spaces. I am @shbermejo. Be sure to join my colleague @ClaraGCarro next week for Part 2 of this #ERA22 update!