Skip to main content
Complement System and Iptacopan Therapeutic Pathway Illustration

Complement Corner: Latest Advances in Complement-Targeted Therapies for C3GN

Exploring breakthrough treatments including Iptacopan for C3 glomerulonephritis (C3 GN), C3G, and PNH - Highlights from ASN Kidney Week 2024

Stay informed about groundbreaking developments in complement-targeted therapeutics, including Iptacopan and other innovative treatments. Our expert analysis covers the latest clinical trials and research in complement cascade modulation - essential for treating rare diseases like C3 glomerulonephritis (C3 GN), C3 glomerulopathy (C3G), paroxysmal nocturnal hemoglobinuria (PNH), and other complement-mediated disorders.

At UKidney's Complement Corner, we provide comprehensive coverage of factor B inhibitors, complement pathway therapeutics, and emerging treatment approaches for C3 glomerulonephritis (C3 GN). Our platform delivers valuable insights for nephrologists, hematologists, researchers, and patients seeking the latest advances in complement-targeted therapies and clinical outcomes.

Join our community to receive expert updates on complement inhibition strategies, real-world evidence, and transformative therapies reshaping the treatment landscape for complement-mediated diseases, including C3 glomerulonephritis (C3 GN). Subscribe now for exclusive access to our latest analyses and clinical insights.

  • Loading presentation 1...

    APPEAR C3G Trial

    A Pivotal Phase 3 Study of Iptacopan in C3 Glomerulopathy

    Duration: 4:39
    • The APPEAR trial is a pivotal clinical trial for treating C3G
    • Patients were randomized to receive either Iptacopan or placebo
    • After 6 months, all participants transitioned to Iptacopan
    • Clinical outcomes were measured at 6-month and 12-month marks
    • Key exclusions: Transplant patients
    • Patient Demographics:
      • Baseline GFR: ~90
      • Most on RASI therapy (ACE or ARB)
      • Approximately 40% on immunosuppression
    • The trial enrolled younger patients with preserved kidney function
    • Patients typically receive supportive therapies and adjunctive immunosuppression
    • Trial Significance:
      • Represents development of targeted therapy for C3G
      • No prior targeted therapies existed
    • Key efficacy outcomes:
      • Normalization or improvement of C3 levels
      • Significant reductions in proteinuria
      • Stabilization of eGFR compared to pre-trial slopes
    • 6-month data:
      • 35% reduction in proteinuria, sustained from 3 to 12 months
      • Similar reductions in crossover patients
    • 12-month outcomes:
      • eGFR slope stabilization noted compared to pre-trial decline
      • Indicates kidney protection and potential to avoid ESKD
  • Loading presentation 1...

    Spotlight on Complement

    Latest Advances in Complement Biology and Clinical Applications

    Duration: 3:29
    • Complement biology is rapidly advancing; significant growth since Girard's training
    • Focus at ASN 2024 on:
      • Primary complement-mediated diseases
      • Complement involvement in other diseases
    • Emphasis on comprehensive complement evaluation
    • Evaluations crucial for therapy decisions and transplant workup
    • Tools include:
      • Functional assays for studying complement cascade
      • Key assays: C5b-9, antibodies like C3 nephritic factor
    • Acknowledge the potential for genetic diseases requiring comprehensive testing
    • Importance of kidney biopsy:
      • Essential to differentiate from mimicking diseases
      • Provides prognostic information besides diagnosis
    • Need for re-biopsy over time to assess disease progression
    • Recognition of Canadian experts and presentations at ASN
    • Desire for standardized care protocols
    • Aspirations for unified genetic and serological testing framework
    • Goal of centralized specialty lab for validated testing
  • Loading presentation 2...

    Spotlight on Complement Part 2

    Exploring Advanced Complement Biology and Therapeutic Innovations

    Duration: 4:45
    • My name is Ratna Samanta.
    • I'm a nephrologist at the Montreal General Hospital in Montreal, Quebec, Canada.
    • I serve as the site director for nephrology.
    • I also run the glomerulonephritis and lupus vasculitis clinics here.
    • At the ASN, it's been exciting to hear talks on complement-mediated diseases and potential therapies.
    • Outcomes have been challenging in recent years.
    • We're now focusing on proteinuria reduction and EGFR slopes as key outcome measures.
    • We hope that reduced proteinuria indicates reduced inflammation and damage, particularly to podocytes.
    • Podocytes are responsible for protein loss.
    • It's a vicious cycle: more protein loss leads to more damage, and so on.
    • We hope that by reducing proteinuria, we can reduce inflammation and damage, ultimately leading to better outcomes and decreased progression to end-stage renal disease.
    • We often see a linear decline in kidney function in these patients.
    • Fifty percent develop end-stage kidney disease within 10 years.
    • This is a rapid decline compared to the normal 1% annual loss after age 30.
    • Therefore, any improvement or stabilization of EGFR and reduction in the progression to kidney failure is a positive sign.
    • With more data, we hope to see a more favorable slope, but for now, stabilization and slowing the decline are our goals.
    • It's important to obtain nephritic factors like C3, C4, and C5 early on to determine if patients are positive or negative.
    • Posters at the ASN suggest these factors have prognostic value.
    • We also need to monitor these levels as patients undergo different therapies, whether immunosuppressive or conservative.
    • The Valiant study suggested a reduction in C3C staining on kidney biopsies, and we need to investigate if this is a prognostic factor.
    • Finally, monitoring C5b-9 levels can help assess ongoing disease activity, but we need more data to determine its prognostic value.
    • We've only begun to understand the complement cascade and how to assess which factors confer risk, benefit, or prognosis, including recurrence.
    • Patients are not all the same, and there are different binding epitopes for these molecules.
    • We need better, potentially less invasive, biomarkers.
    • We hope that a reduction in proteinuria indicates less inflammation.
    • However, if this reduction is associated with an increase in creatinine and a decrease in renal function, it may simply reflect decreased filtration.
    • Ideally, we would biopsy everyone's kidneys as their proteinuria decreases to see if there's a correlation, but we don't have that information yet.
  • Loading presentation 4...

    Clinical Applications in Nephrology

    Advanced Therapeutic Approaches and Patient Management Strategies

    Duration: 6:07
    • My name is Ratna Samantha, and I'm a nephrologist at the Montreal General Hospital in Montreal, Quebec, Canada.
    • I'm the site director for nephrology at the hospital, and I run the glomerulonephritis and lupus vasculitis clinics.
    • Unfortunately, whether a patient has a native or transplant kidney, the underlying disease can recur.
    • Many treatments are essentially 'bandage solutions,' and we see recurrence in transplant kidneys in at least 50% of cases, sometimes higher.
    • This depends on risk factors like nephritic factors or genetics.
    • Some centers may even refuse transplants for these patients, while others proceed.
    • Even with heavy immunosuppression, transplant patients can still develop the disease.
    • Studies have shown that transplant patients with recurrent C3G can progress to end-stage kidney disease faster than those with native kidneys.
    • We need better therapies to address this.
    • Our goal in medicine should be preventative care.
    • It's better to prevent diseases than to react after they occur.
    • Preventative action leads to a better quality of life, allowing people to live their lives without being limited by disease.
    • We need better therapies in general.
    • Data suggests a minimum of 50% recurrence in transplants.
    • This can rise to almost 80% or even 100% depending on the initial condition, such as C3GN, dense deposit disease, nephritic factors, or underlying genetic components.
    • Given this high baseline risk, it's imperative to have proper therapies, especially since patients are already on immunosuppression.
    • These are just managed solutions; we need better therapies.
    • It's crucial to intervene before proteinuria or creatinine levels start to rise.
    • Preventing these issues from the outset will help ensure the kidney and the person stay healthier for longer.
    • We should focus on preventing the disease from occurring.
    • Targeted therapies are very important.
    • It's exciting that Canada may soon have access to new medications.
    • Canada sometimes lags behind other countries in access to these medications.
    • It's also important to have the ability to test for different elements of the complement cascade, with equitable access across Canada, not just in certain cities.
    • It will be a brighter future when all provinces can use these therapies prophylactically to prevent kidney progression, including in transplant patients.
    • The KDIGO guidelines for glomerular diseases were revised around 2021.
    • Several of us interested in glomerular diseases wrote a Canadian commentary on these guidelines, which we've submitted for publication.
    • A key message from all the authors was the need for more equitable access to testing across all provinces and regions, both urban and rural, as well as affordable access to therapies.
    • Testing is pointless if you can't do anything about the results.
    • With newer therapies being approved in Canada, it's important for all clinicians to be able to treat their patients.
    • Even though GNs are rare, they are the third leading cause of kidney failure in Canada.
    • It's vital to treat these patients quickly to prevent this high rate of renal failure.

Featured Speakers

Leading experts in nephrology and complement-mediated diseases

Dr. Louis Girard

Dr. Louis Girard

University of Calgary

MD, MBT, FRCPC

Nephrologist and Clinical Associate Professor

Medical Director of Glomerulonephritis

Dr. Louis Girard joined the Division of Nephrology at the University of Calgary in July of 2010. He focuses on clinical immunology and infectious diseases in chronic kidney disease patients.

Dr. Ratna Samanta

Dr. Ratna Samanta

McGill University Health Center

MSc, MDCM, FRCPC

Associate Professor, Division of Nephrology

MGH Site Director for Nephrology

Dr. Samanta is an Associate Professor at McGill University, with expertise in Chronic Disease Epidemiology from Yale University and specialized training in Glomerulonephritis from the University of Toronto.

Pre-Test Assessment

Please complete this brief assessment before viewing the content

Post-Test Assessment

Please complete this brief assessment to finish the module

ukidneyisup