Thank you to our PARASOL partners @nkf-professionals.bsky.social @asnkidney.bsky.social and Nephcure, PARASOL PIs Laura Mariani and Matthias Kretzler, lead biostatistician Abigail Smith, Margaret Helmuth and the data analysis core at @miktmc.bsky.social, and EVERYONE involved in the project!
More than 100 years after #FSGS was first described, we have the first FDA-approved treatment. A proud day for the collaborative #ParasolProject! With the global community uniting to transform glomerular health, this is only the beginning. ⛱️
Take-home from WCN26:
IgAN treatment is shifting from nonspecific immunosuppression to pathway-directed therapy.
The debate is no longer whether to treat, but where in the pathway to intervene first. 🧵 (10)
#GlomerularDisease
#ISNWCN
Future IgAN management may involve combination or sequential therapy:
• Gut-targeted immunomodulation
• Complement inhibition
• Possibly BAFF/APRIL blockade
Precision treatment for a heterogeneous disease. 🧵 (9)
#GlomerularDisease
#ISNWCN
🔑 clinical question:
Should therapy first target the cause of IgAN
or the mechanism of kidney injury?
This remains unresolved and likely depends on patient phenotype. 🧵(8)
#GlomerularDisease
#ISNWCN
However, mechanisms differ.
Nefecon → modifies disease origin (gut immune system)
Complement inhibitors → block final inflammatory pathway in kidney
Upstream control vs downstream protection. 🧵 (7)
#GlomerularDisease
#ISNWCN
In APPLAUSE-IgAN:
Iptacopan reduced the risk of the composite kidney failure endpoint by 43% vs placebo
(HR ≈0.57).
Strong signal for complement blockade in IgAN progression. 🧵 (6)
#GlomerularDisease
#ISNWCN
Clinical trials show both strategies slow disease progression.
NefIgArd (Nefecon):
✔ Reduced proteinuria
✔ Slower eGFR decline
APPLAUSE-IgAN (iptacopan):
✔ Reduced proteinuria
✔ Lower risk of kidney failure events
🧵 (5)
#GlomerularDisease
#ISNWCN
Complement inhibitors such as Iptacopan:
• Block the alternative complement pathway
• Reduce inflammatory injury in the glomerulus
They act downstream, after immune complexes reach the kidney. 🧵 (4)
#GlomerularDisease
#ISNWCN
Targeted-release budesonide (Nefecon):
• Acts in the terminal ileum
• Suppresses mucosal immune activation
• Reduces production of pathogenic Gd-IgA1
In short: it targets the upstream driver of disease. 🧵 (3)
#GlomerularDisease
#ISNWCN
IgAN pathogenesis follows a multi-hit model:
1️⃣ Mucosal immune dysregulation → galactose-deficient IgA1
2️⃣ Autoantibody formation
3️⃣ Immune complex formation
4️⃣ Glomerular deposition + complement activation
Therapies target different steps. 🧵 (2)
#GlomerularDisease
#ISNWCN
♨️ Debate at WCN26:
Should complement inhibition be considered before targeted-release budesonide in patients with IgAN at risk of progression?
A key discussion between upstream vs downstream treatment strategies in IgAN. 🧵(1)
#ISNWCN
#GlomerularDisease
#ISNWCN “KDIGO IgAN Session” discussing so interesting cases and perspectives 🇺🇸🇨🇳🇯🇵
🔎Effect of therapies on GFR loss and proteinuria
🎯Novel agents
👉🏻Disease activity and clinical background are important to determine appropriate therapy
#GlomerularDisease #KidneyHealthMatters 🌎🫘🌸
“Understanding and Treating Complement-Mediated Glomerular Disease” #ISNWCN #ISGD
✅KPMP: right treatment, right person, right time
🧬Haplotype and Disease Penetrance- Genetic testing
❌C5b-9: more severe disease
🖊️C5a in AAV - complement therapies
🎯”RESET into homeostasis” #GlomerularDisease
🌟 Enjoying our #WCN2026 coverage?
A heartfelt thank you to our incredible ISGD social media ambassadors, Dr. @gabyneph.bksy.social and Dr. Belén Gallegos, for bringing us the latest updates and insights in glomerular disease and keeping our community informed and engaged 🙌
#ISGD #GlomerularDisease
QR code for https://www.nephjc.com/news/nephjc-editorial-internship
Applications are open for the next class of the #NephJC internship
Apply here www.nephjc.com/news/nephjc-... or scan the QR code
#ISNWCN
⛩️ Together in Yokohama at #ISNWCN with presidents of ERA, @theisn.org and @isgd.bsky.social ! ⛩️ @rosertorra.bsky.social, Marcello Tonelli, and @tobias-b-huber.bsky.social + Ron Gansevoort
At WCN’26, Tobias Huber highlighted the mission of the ISGD: uniting a 🌎 community to connect, educate, and advance research to improve care for patients with #GlomerularDisease
With 1,700+ members across 102 countries, #ISGD is building a 🌎 network for innovation and collaboration in 🫘 disease
Heather Reich ISGD Chair of the Membership & Accreditation Committee, is present at the WCN’26
🤩 A great session about exploring the role of APRIL in IgAN
👉🏻 A great discussion of clinical scenarios
#ISGD
#GlomerularDisease
#ISNWCN
Amazing! Paola Romagnani #ISGD #ISNWCN with “Podocytopathies: Knowns and Unknowns”
👉🏻Podocyte loss and regeneration
👀Autoimmune, genetic, adaptive, infectious, toxic, monoclonal
🎯Anti-slit autoantibodies-> ⬇️ prognosis
#GlomerularDisease #Yokohama 🌸
Our ISGD president Tobias Huber is present at the WCN’26 🌸
👉🏻 His first session of the day: Kidney tissue-specific gene targeting
🦠 Adenovirus as a potential vector for gene targeting therapies
#ISNWCN
#GlomerularDisease
#ISGD
🤔 Where is pathogenic IgA produced❓
👉🏻 B cells induced in MALT can migrate to the bone marrow and differentiate into IgA-PC there
💉💊 We have emerging therapies to target B cells in Ivan but we still need a better understanding of the pathophysiology
#ISNWCN
@theisn.org
🤔 Where is pathogenic IgA produced❓
👉🏻 B cells induced in MALT can migrate to the bone marrow and differentiate into IgA-PC there
💉💊 We have emerging therapies to target B cells in Ivan but we still need a better understanding of the pathophysiology
#ISNWCN
@theisn.org
🤔 What makes IgA pathogenic in IgAN❓
👉🏻 A subgroup of GdIgA1with strong affinity for the glomerulus 🫘
💡 IgA type anti-MEsangial Cell Antibodies (Ig-MESCA) are GdIgA1-Ab.
🎯 Mesangial cells
🧫 Molecular mimicry with oral bacteria
#ISNWCN
@theisn.org
INShore Phase 3 trial: Obinutuzumab vs MMF in childhood-onset FRNS/SDNS to maintain remission
85 patients / 9 countries
Type II anti-CD20 therapy → ⬇️ B-cell depletion
Primary endpoint met: sustained remission at 52 wks significantly ⬆️ w/obinutuzumab
#ISNWCN
@ISNKidneycare
So interesting! “Cutting Edge Science in Nephrotic Syndrome/FSGS” #Yokohama #ISNWCN
*Autoimmune Diseases treatments
*B cell depletion - How broad?
*Prognosis given by antibodies
*Anti-human and anti-mouse CD39 antibodies
Amazing treatment options #GLOMERULARDISEASE
"Finally in #Yokohama for 'Renal Pathology: Native Kidney Disease Pathology.' Covering IgG4-related disease, parasitic glomerular lesions, and genomics in Undeterminate Kidney Disease. Follow for more updates. #Nephrology #GlomerularDisease #Genomics
🤔 Do not know which session to attend in the WCN’26?
@Tobias_B_Huber is giving this amazing session:
📌 Autoantibodies targeting podocyte-specific antigens in primary nephrotic syndrome
🗓️ Sunday, 29 March
⏰ 15:50
📍 304
👀 Attending the WCN’26?
👉🏻 Do not miss this interesting talk:
🐺 CAR-T cell therapy in lupus
🗓️ Monday, 30 Mar 2026
⏰ 09:50
📍 301-302
Speaker: @BradRovin
#ISNWCN
@ISNKidneycare
Don't miss this chance to learn from expert faculty and transform patient care.
Learn more: www.is-gd.org/rpa-isgd-ctb1
#Nephrology #ISGD #ClinicalTrials #MedicalEducation @renalphysicians.bsky.social @tobias-b-huber.bsky.social