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C3 Glomerulopathy: Pathogenesis and Treatment

Syeda Behjat Ahmad1, Andrew S Bomback1

  • 1Division of Nephrology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY.

Advances in Chronic Kidney Disease
|June 20, 2020
PubMed

Insights

C3 glomerulopathy (C3G) is a rare kidney disease caused by complement dysregulation. This review covers C3G pathogenesis and emerging complement inhibitor treatments for C3 glomerulonephritis and dense deposit disease.

Area of Science:

  • Nephrology
  • Immunology
  • Genetics

Background:

  • C3 glomerulopathy (C3G) encompasses C3 glomerulonephritis (C3GN) and dense deposit disease, both rare kidney diseases.
  • These conditions stem from dysregulation of the complement alternative pathway, often due to genetic or acquired defects in regulatory proteins.
  • C3G presents with low serum C3 and C3-dominant immunofluorescence on kidney biopsy, but can be mistaken for other glomerulonephritides.

Purpose of the Study:

  • To review the pathogenesis of C3 glomerulonephritis (C3GN).
  • To survey current and investigational treatment options for C3G.
  • To highlight diagnostic challenges and disease recurrence after transplantation.

Main Methods:

  • Literature review of C3 glomerulopathy.
  • Analysis of complement pathway dysregulation in C3G.
  • Summary of clinical trials and approved therapies.

Main Results:

  • C3G pathogenesis involves complement alternative pathway dysregulation.
  • Both C3GN and dense deposit disease are progressive and can recur post-transplant.
  • Complement inhibitors show promise as targeted therapies.

Conclusions:

  • C3G requires understanding of complement biology for diagnosis and management.
  • Targeted complement inhibition represents a significant advancement in C3G treatment.
  • Further research is needed to optimize therapeutic strategies and address disease recurrence.

Keywords:
ComplementDense deposit diseaseMembranoproliferative glomerulonephritis

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