C3 glomerulopathies: dense deposit disease and C3 glomerulonephritis

Abstract

Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are types of membranoproliferative glomerulonephritis classified as C3 glomerulopathies. These conditions are characterized by an increased number of intraglomerular cells and diffuse thickening of the glomerular capillary walls, along with the deposition of C3 and minimal or absent immunoglobulin deposits. The underlying cause of both DDD and C3Gn is an abnormal activation of the alternative complement pathway, which can result from acquired or genetic alteration. In acquired forms of DDD and C3GN, the dysregulation of the alternative pathway is commonly induced by the presence of C3 nephritic factors (C3NeFs), which are autoantibodies that stabilize C3 convertase. Both DDD and C3GN can affect individuals of any age, but DDD is primarily diagnosed in children, whereas C3GN tends to be diagnosed at a significantly higher age. The presenting features of these diseases are variable and may include proteinuria, hematuria, hypertension, or kidney failure. A common finding in these diseases is low serum C3 levels with normal serum C4 levels. Chronic deterioration of renal function is commonly observed in DDD and C3GN, often leading to end-stage renal disease (ESRD), especially in DDD. Kidney transplantation outcomes in patients with these conditions are characterized by histological recurrence, which may contribute to higher rates of allograft failure.

Plasma and Kidney Proteome Profiling Combined with Laser Capture Microdissection Reveal Large Increases in Immunoglobulins with Age

“…Various glomerular diseases are associated with the deposition of C3 in the glomeruli. For example, membranoproliferative glomerulonephritis (MPGN) is characterized by the accumulation of C3 in the glomerular basement membrane [ 27 ]. This deposition can result from the dysregulation of the complement system or the formation of immune complexes within the glomerulus.…”

Updates on C3 Glomerulopathy in Kidney Transplantation: Pathogenesis and Treatment Options

“…Furthermore, when C3GN is associated to monoclonal gammopathies, it is important to treat the hematological disease before transplantation since hematological response is associated with a better renal survival and a lower risk of early graft recurrence. Although in recent years, probably thanks to new potential drugs, attention to C3GN has increased [ 88 , 89 , 90 ], further studies are needed to better understand the pathogenesis, course and potential therapy for C3GN both on native kidneys and on transplanted kidneys.…”