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Current and Emerging Therapies for C3 Glomerulopathy and Primary (Idiopathic) Immune Complex Membranoproliferative

David Kavanagh1,2, Gema Ariceta3, Marina Vivarelli4

  • 1Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.

Kidney International Reports
|January 16, 2026
PubMed

Insights

Targeted complement inhibitors show promise for C3 glomerulopathy (C3G) and immune complex membranoproliferative glomerulonephritis (IC-MPGN). These therapies address underlying complement dysregulation, offering new hope for patients with these rare kidney diseases.

Area of Science:

  • Nephrology
  • Immunology
  • Pharmacology

Background:

  • C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) are rare kidney diseases driven by complement system dysregulation.
  • These conditions lead to C3 deposition in glomeruli, causing kidney failure in up to 50% of patients within 10 years.
  • Traditional treatments focused on supportive care and immunosuppression, lacking specific therapies for the underlying pathology.

Purpose of the Study:

  • To review the current understanding and remaining questions regarding complement inhibitors in C3G and IC-MPGN.
  • To evaluate the impact of complement inhibitors on key efficacy endpoints like proteinuria, eGFR, and kidney histology.
  • To discuss controversies surrounding patient selection, treatment duration, and monitoring for complement inhibitor therapy.

Main Methods:

  • Review of recent phase 3 clinical trial data for complement inhibitors (iptacopan and pegcetacoplan).
  • Analysis of surrogate endpoints for treatment efficacy in C3G and IC-MPGN.
  • Discussion of clinical controversies and future directions in complement inhibitor therapy.

Main Results:

  • Phase 3 trials of iptacopan (factor B inhibitor) and pegcetacoplan (C3/C3b inhibitor) have demonstrated positive results in adults and adolescents with C3G or IC-MPGN.
  • These targeted therapies address the underlying complement dysregulation, a significant advancement over previous treatment strategies.
  • The review synthesizes data on surrogate markers of efficacy, including proteinuria, eGFR, and histological improvements.

Conclusions:

  • Targeted complement inhibitors represent a significant therapeutic advance for C3G and IC-MPGN, offering improved prognosis.
  • Further research and consensus are needed regarding optimal patient populations, treatment duration, and monitoring strategies.
  • These innovative therapies hold promise for patients with historically poor long-term outcomes.

Keywords:
C3GIC-MPGNcomplement 3 glomerulopathycomplement inhibitioncomplement systemimmune complex membranoproliferative glomerulonephritis

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