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Introduction to C3 Glomerulopathy (C3G) and Primary Immune Complex-Mediated Membranoproliferative Glomerulonephritis (IC-MPGN): Two different rare kidney diseases driven by C3 dysregulation1-11

C3G and primary IC-MPGN are rare, chronic and heterogeneous kidney diseases driven by C3 dysregulation that result in irreversible kidney impairment.1–11

Clinical Background

These diseases present with a spectrum of symptoms that overlap with other glomerulopathies, leading to frequent misdiagnosis, treatment delays and untreated renal damage.3,5,6,9

The initial clinical presentation of C3G and primary IC-MPGN can vary widely from asymptomatic haematuria and proteinuria with preserved renal function to nephrotic syndrome and/or rapidly progressive glomerulonephritis.7

Renal manifestations include haematuria, proteinuria, hypoalbuminaemia, and serum 3 hypocomplementemia, although this is not essential for diagnosis as low serum C3 levels are found in half of patients.7,12,13

Beyond the kidneys, patients may also experience extrarenal manifestations such as acquired partial lipodystrophy, oedema, and early-onset drusen-like deposits in the retina.7

Similar to the heterogeneity observed at initial clinical presentation, the disease course is highly variable. Some patients experience acute flares, while others follow a more gradual progression to kidney failure.5-7

C3, complement 3; C3G, C3 glomerulopathy; IC-MPGN, immune complex-mediated membranoproliferative glomerulonephritis.

References:

  1. Smith RJH, et al. Nat Rev Nephrol 2019;15:129–43.
  2. Cook HT & Pickering MC. Nat Rev Nephrol 2015;11:14–22.
  3. Noris M & Remuzzi G. Nephrol Dial Transplant 2024;39:202–14.
  4. Prevalence and incidence of rare diseases: Bibliographic date. Orphanet Report Series, Rare Disease collection. 2024; Number 1: diseases listed in alphabetical. Available at: https://www.orpha.net/pdfs/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf. Accessed September 2025.  
  5. Meuleman MS, et al. Semin Immunol 2022;60:101634.
  6. Feldman DL, et al. Voice of the patient. Report of externally-led patient-focused drug development meeting on: Complement 3 glomerulopathy (C3G). Available at: https://www.kidney.org/sites/default/files/C3G_EL-PFDD_VoP-Report_3-29-18.pdf. Accessed September 2025.
  7. Caravaca-Fontán F, et al. Nephron 2020;144:272–80.
  8. Fervenza FC, et al. Nephrol Dial Transplant 2012;27:4288–94.
  9. Mastrangelo A, et al. Front Pediatr 2020;8:205.
  10. Anders HJ, et al. Nat Rev Immunol 2023;23:453–71.
  11. Bomback AS, et al. Kidney Int 2018;93:977–85.
  12. Politano SA, et al. Prim care 2020;4:597–613
  13. Servais A, et al. KI 2012;82:452-464
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