Definition

• C3 glomerulopathy comprises C3 GN and dense deposit disease (DDD); both are characterized by C3- predominant deposits within glomeruli, and sometimes tubules, with little or no immune complexes.

Aetiology

 • These diseases are related to dysregulation of the alternative pathway of complement activation (inherited or acquired) and can be due to mutation or autoimmune dysregulation of various components of the alternative pathway (e.g. DDD is often due to a C3 nephritic factor which is an autoantibody against C3; C3 GN can be due to mutations in factor H, a protein that regulates activation of the alternative pathway).

Typical pathological features

• Variable glomerular hypercellularity.

 • Immunofluorescence: C3 predominance, with or without immunoglobulins.

• Electron microscopy: electron- dense deposits in variable locations within the glomeruli; DDD is characterized by electron- dense transformation of the glomerular and tubular basement membranes (Fig. 1).

Fig1. Acute post- streptococcal GN on electron microscopy: electron- dense deposits in a subepithelial location with a ‘hump’- like shape (arrows)

Fig2. Dense deposit disease on electron microscopy. Long areas of electron density are present within the glomerular basement membrane (arrows)

Prognosis

• Depends on the underlying pathogenetic mechanism; cases with autoantibodies may respond well to immunosuppression or removal of the antibody by plasmapheresis, whereas cases due to defective proteins may respond well to replacement of the defective proteins by fresh plasma.