2) This #accredited #tweetorial is supported by an independent educational grant from Travere and is intended for healthcare providers. FOLLOW US for regular programs by expert faculty!
— @CKD_ce (@ckd_ce) August 9, 2022
4a) Let’s start with a case. 24 ♂️ with incidentally diagnosed #hypertension referred for work up and second opinion. No meds.
— @CKD_ce (@ckd_ce) August 9, 2022
BP 155/95. BMI 35. #UPCR 1.5 g/g, no edema
Ultrasound imaging: both kidneys 10 cm, no focal lesions
Ocular exam: Fundus hypertonicus II pic.twitter.com/CE48YSDknX
5a) Actually, you couldn't get that wrong! All are correct. OK, maybe not as nice as we should have been . . . but
— @CKD_ce (@ckd_ce) August 9, 2022
A: Damage of glomerular filter: Albuminuria (UACR) is at least 75% of UPCR
B: Prox tubule injury (ß2 or a1MG loss, UACR<75% of UPCR)
(cont)
6) Back to our case: (tweet 4a):
— @CKD_ce (@ckd_ce) August 9, 2022
👉paraprotein unlikely at 24Y
👉tubular proteinuria also possible but UACR = 80% of UPCR
👉hence glomerular proteinuria is most likely explanation
👉low birthweight, early onset #HTN, small #kidneys in an obese young adult suggest …?
8) How is causality here?
— @CKD_ce (@ckd_ce) August 9, 2022
👉Glomerular proteinuria is the sign of hemodynamic overload/hyperfiltration = barotrauma to the glomerular filtration barrier.
👉#HTN is the sign of metabolic overload and a positive #sodium chloride balance and activation of the #RAAS. pic.twitter.com/21LbHpoSIn
10. What we do about #obesity in this case?
— @CKD_ce (@ckd_ce) August 9, 2022
A)Eat↓ and better, drink water/tea/coffee, not soft drinks/beer
B)Regular exercise that makes u sweat
C)Bariatric surgery
D)s.c. tirzepatide once weekly
12) What would a kidney #biopsy show in our patient?
— @CKD_ce (@ckd_ce) August 9, 2022
👉Large #gloms: ↑ filtration surface = ↓ glomerular pressure
👉#podocyte hypertrophy: to cover ↑filtration surface
👉Adaptive #FSGS: as a sign of #podocyte loss (too much shear stress) pic.twitter.com/aAvvdbHC5N
14) Let’s look again to the different causes of #FSGS pic.twitter.com/YjmWJ8Gg9o
— @CKD_ce (@ckd_ce) August 9, 2022
15a) But how to address proteinuria in FSGS, if not with steroids, et al?
— @CKD_ce (@ckd_ce) August 9, 2022
👉Eliminate #podocyte toxins, infections, or any other causative agents
👉Control risk factors for glom. hyperfiltration (DM, obesity, high salt intake)
(cont)
16a) We control proteinuria in #FSGS by
— @CKD_ce (@ckd_ce) August 9, 2022
👉Eliminate causative agents whenever possible
👉Control #DM, obesity, high salt intake is standard in all forms of CKD
👉Drugs that ↓ glom. hyperfiltration are standard in all forms of CKD
(cont)
17a) So: the significance of #proteinuria in #FSGS?
— @CKD_ce (@ckd_ce) August 9, 2022
👉It`s a diagnostic marker for all forms of FSGS.
👉It`s a biomarker of activity & guides treatment in autoimmune forms of FSGS
👉It’s an indicator of hemodynamic overload of the remaining nephrons in FSGS-related #CKD
(cont)
18) Whew! After years of stagnation, we are starting to understand better. Think on how these new concepts may impact on other glomerular disorders –and return tomorrow for more a focused view on proteinuria in IgAN & your link to 🆓CE/#CME! pic.twitter.com/JkfyNu3naE
— @CKD_ce (@ckd_ce) August 9, 2022
19b) We wanted to post a correction to yesterday's graphic in tweet 15 (below) . . . we had one too many negative indicators. Indeed, steroids ARE indicated in the treatment of autoimmune podocytopathies pic.twitter.com/u0226OOgMs
— @CKD_ce (@ckd_ce) August 10, 2022
20b)
— @CKD_ce (@ckd_ce) August 10, 2022
👉Vasculitis responds well to steroids
👉#RPGN with crescents may benefit from cyclosporine
👉Unmet needs: steroid toxicity, missing RCT evidence pic.twitter.com/x7SNDXeIWH
22a) Chronic #IgAN
— @CKD_ce (@ckd_ce) August 10, 2022
👉Only kidney biopsy secures Dx
👉More common in adult ♂️ but time of onset of chronic #IgAN often unclear
👉Autoimmune nature less obvious (no effect of MMF, RTX, …)
(cont)
23a) Chronic #IgAN, role of #proteinuria:
— @CKD_ce (@ckd_ce) August 10, 2022
👉Diagnostic indicator of GN
👉Unreliable marker of immunological disease activity
because UPCR can be a sign of other factors
👉If good marker of response to steroids, is unclear pic.twitter.com/UhBEEap23w
24) Let’s look at another case:
— @CKD_ce (@ckd_ce) August 10, 2022
42♂️ with HTN, biopsy proven IgAN. BMI 32. History of AKI and 3d of HD after car crash polytrauma.
Now SCr 1.0, microhematuria, #UPCR initially 2.5 and 2.3 after GP started 10 mg ramipril/5 mg amlodipine 6 months ago pic.twitter.com/CHc5qrGyeW
26) Actually, both C and D are correct:
— @CKD_ce (@ckd_ce) August 10, 2022
We cannot be sure if #IgAN is active as long as he is on a dihydropyridine CCB that increases hyperfiltration via its vasodilatory effect. In addition, likely low nephron no due to previous severe #AKI
28) C is correct:
— @CKD_ce (@ckd_ce) August 10, 2022
We cannot be sure if #IgAN is active as long as he eats frozen pizza, salty popcorn, crackers, salami, salty cheese, …. that all increase hyperfiltration via hypervolemia pic.twitter.com/Lv3C6mcqGE
30) C is correct: We cannot be sure if #IgAN is active as long as his kidneys are hyperfiltrating for obesity, which implies glomerular hyperfiltration pic.twitter.com/qyVdAAnmMa
— @CKD_ce (@ckd_ce) August 10, 2022
32a) C is correct because:
— @CKD_ce (@ckd_ce) August 10, 2022
👉#UPCR = unreliable marker of activity in chronic #IgAN. Gold standard: repeat biopsy, showing, e.g.,
👉No of glom. CD206+ macrophages: 40-fold ↑probability to respond to steroids, as per https://t.co/RqD6Uup2id
(cont) pic.twitter.com/qgWg6MC7oH
33b)
— @CKD_ce (@ckd_ce) August 10, 2022
👉RCTs include too many inactive pts who can't benefit from immunomodulators ➡️effect size↓, chances that trial fails↑
👉Ph 3 #IgAN RCTs should not rely on UPCR but on GFR as primary endpoint
34) Is this specific for #IgAN? No, because the same principles apply for all forms of #GN: pic.twitter.com/NUGY6I4lSB
— @CKD_ce (@ckd_ce) August 10, 2022
36) Back to our case (tweet 24 et seq) with 2 more questions:
— @CKD_ce (@ckd_ce) August 10, 2022
Would it still matter to further reduce a #UPCR of 0.8
A)Yes, because the lower the better
B)No, because the slope of GFR is the same below a #UPCR of 1
38a) Daniel C Cattran and colleagues reviewed these two questions and found:
— @CKD_ce (@ckd_ce) August 10, 2022
🔑 In contrast to #MGN and #FSGS, #IgAN pts benefit from reducing #UPCR below 1 but in this range annual GFR loss is close to normal
(cont)
39) And that's it! YOU MADE IT! 0.5h CE/#CME credit. Go claim your certificate at https://t.co/AtRCgeIUxH. I am @hjanders_hans and I invite you to FOLLOW @ckd_ce (and @cardiomet_ce) for more outstanding education and 🆓credit for 🇪🇺🇬🇧🇨🇦🇺🇸 clinicians!
— @CKD_ce (@ckd_ce) August 10, 2022