2) Statement of accreditation and author disclosures can be found at https://t.co/PHlIpplEO4. No industry funding was provided for this program, which is accredited by @academiccme.
— @CKD_ce (@ckd_ce) October 9, 2024
So . . .
How much do you know about #IgAN? ?
4a) Answer B.
— @CKD_ce (@ckd_ce) October 9, 2024
Yes, we know now that #IgAN is not benign.
Up to 30% of pts will progress to #ESKD at 20y.
The presentation is heterogenous & includes
✅Asymptomatic hematuria
✅Asymptomatic proteinuria
✅Nephritic syndrome
(cont)
5) #IgA dominance on renal biopsy is the hallmark of #IgAN?
— @CKD_ce (@ckd_ce) October 9, 2024
But it is not specific
Ask:
Is it primary IgAN or secondary IgAN? ?
and..
Is it an alternative IgA dominant #GN?
✅ IgA- dominant IRGN
✅ IgA Vasculitis pic.twitter.com/avHGjJivjH
7) What is the pathogenesis of IgAN?
— @CKD_ce (@ckd_ce) October 9, 2024
Let’s recap the 4 -hit hypothesis
1⃣ Production of galactose deficient IgA1 in mucosal tissue
2⃣ Formation of Auto Ab against IgA1
3⃣ Formation of IgG-Gd-IgA1 immune complexes(IC)
4⃣ Deposition of IC in the kidneyhttps://t.co/QMP9T9vlI8 pic.twitter.com/BFPILjhBkj
9a) #GdIgA & Anti IgA antibody complex deposition is followed by complement activation, inflammation & tissue injury.
— @CKD_ce (@ckd_ce) October 9, 2024
10) Answer is D. Low complement levels are not characteristically seen in #IgAN.
— @CKD_ce (@ckd_ce) October 9, 2024
However the other features may be present and support the role of complement in pathogenesis.
This suggests complement inhibition may be a therapeutic strategy.
12) Can we use the renal #biopsy to prognosticate outcomes in #IgAN?
— @CKD_ce (@ckd_ce) October 9, 2024
13b) Additional criteria
— @CKD_ce (@ckd_ce) October 9, 2024
✅MEST score
✅Age
✅Medication use (RAAS blockade/ immunosuppression)
✅Race#NephMadness @Dilushiwijay pic.twitter.com/LF8IKVVvYs
14b) Do you use the International IgAN risk prediction risk prediction tool to make management decisions?
— @CKD_ce (@ckd_ce) October 9, 2024
16) Let’s move on to treatment. In treating #IgAN, broadly we should have TWO aims
— @CKD_ce (@ckd_ce) October 9, 2024
1) Prevent IC formation and IC-mediated injury
2) Prevent #nephron loss (Non-specific measures to halt #CKD progression)
Optimal supportive care for all
17b (cont)
— @CKD_ce (@ckd_ce) October 9, 2024
& suppressing the inflammation secondary to glomerular deposition of complexeshttps://t.co/Exz4EaJ2fC pic.twitter.com/YYdLhzqvw5
19a) The best evidence for treatment comes from RCTs and their meta-analyses. However, there are many challenges in clinical trials in #IgAN
— @CKD_ce (@ckd_ce) October 9, 2024
? It is a slowly progressive disease → clinical outcomes are less likely to be met within the duration of a trial
20) One solution to some of these problems is to use surrogate markers of kidney disease progression as trial endpoints.
— @CKD_ce (@ckd_ce) October 9, 2024
Change in proteinuria has been approved as endpoint for accelerated approval of drugs for treatment of IgAN by the FDAhttps://t.co/GFjAuBtjSw
21b) #SGLT2i were shown to delay the primary composite endpoint of a sustained reduction in eGFR >50%, ESKD, or death from kidney disease or CVD.
— @CKD_ce (@ckd_ce) October 9, 2024
✅No heterogeneity in outcome by primary kidney disease#Nephmadness @Dilushiwijay pic.twitter.com/canOYEBP4z
22b) ?
— @CKD_ce (@ckd_ce) October 9, 2024
which led to accelerated approval of #Sparsentan to reduce proteinuria in adults with primary IgA nephropathy who are at risk of rapid disease progression, generally a UPCR ≥ 1.5 g/g@NephJC @husamJZ pic.twitter.com/Or6zN30cf4
24) Now: immunosuppressive tx in #IgAN. These drugs fall into 2 main categories
— @CKD_ce (@ckd_ce) October 9, 2024
1) Drugs to ⬇️formation on GdIgA & IC – eg. BAFF/APRIL inhibitors, MMF
2) Drugs to suppress IC-mediated injury – Steroids (systemic or targeted release), complement inhibitorshttps://t.co/Exz4EaJ2fC pic.twitter.com/SVcBkf0iYz
26a) Systemic Steroids
— @CKD_ce (@ckd_ce) October 9, 2024
The #Stop_IgAN trial failed to show benefit of steroids + Standard of Care (SoC) over SoC alone on clinical outcomes but did demonstrate a proteinuria reduction in #IgAN.
Later trials have been more promising
26c) LOW DOSE systemic steroids may be considered in those at high risk of progression (for whom targeted release preparations are not available- see below).
— @CKD_ce (@ckd_ce) October 9, 2024
⚠️Should be combined with antibiotic prophylaxis due to risk of infections (TESTING trial).#Nephmadness @Dilushiwijay pic.twitter.com/z7eAw2P7Ja
27) Consider risk factors for #SAE on #steroids:
— @CKD_ce (@ckd_ce) October 9, 2024
⚠️ #eGFR <30 ml/min per 1.73 m2
⚠️ #Diabetes and prediabetes
⚠️ #Obesity
⚠️ Latent infections (e.g., viral hepatitis, tuberculosis)
⚠️ Active peptic ulceration
⚠️ Uncontrolled psychiatric illness
⚠️ #Osteoporosis
⚠️ #Cataracts
29a) The #NefIgArd trial which compared targeted release #budesonide and placebo in #IgAN was published in 2 parts :
— @CKD_ce (@ckd_ce) October 9, 2024
Part A (on treatment)
At 9 months- improved eGFR, UPCR, UACR with treatmenthttps://t.co/rUr3qnALF4 pic.twitter.com/2ZyNxaUGyy
30) There are still many questions about steroids?
— @CKD_ce (@ckd_ce) October 9, 2024
❓How many courses are needed?
❓How long should steroids be used for?
❓How can we monitor response?
32) Both #MMF & #HCQ have shown some efficacy in Chinese populations, w/improvements in proteinuria. MMF may have a place as a steroid sparing agent.
— @CKD_ce (@ckd_ce) October 9, 2024
There is no evidence of benefit in non-Chinese pops w/MMF (small studies), & HCQ has not been studied in this population
33b)
— @CKD_ce (@ckd_ce) October 9, 2024
a) Complement inhibition
Iptacopan (inhibitor of complement factor B)https://t.co/1tqk8kSY9r pic.twitter.com/8b3NxE87xH
35a) Meanwhile, old but gold:
— @CKD_ce (@ckd_ce) October 9, 2024
Let’s not forget optimal supportive care
Until recently the mainstay!
✅ Low salt diet
✅ BP control (Standardized office SBP <120mmHg)
✅ RAS blockade- ACEi or ARB for proteinuria
✅ Lifestyle changes- smoking ?, optimizing weight
✅Lipid lowering
36) For more in-depth discussions on some of the landmark trials in IgAN try these links @ajkdblog @landmark_nephhttps://t.co/Qh6sSSOwRr https://t.co/7kwrZDdbJVhttps://t.co/QMP9T9vlI8
— @CKD_ce (@ckd_ce) October 9, 2024
37) Thank you for participating in this tweetorial! We hope you are as excited about the future of #IgAN as we are!
— @CKD_ce (@ckd_ce) October 9, 2024
Claim your FREE credit NOW at https://t.co/MC0eZToxzP and follow us for more CE/#CME in the CKD space!