Form of glomerulonephritis (inflammatory changes of glomerular capillaries) caused by an abnormal immune response with deposits of immune complex. Certain cells in the capillary wall (mesangial cells) increase in number and the parts of the glomerular membranes change in structure.
Persistent and slowly progressive
Types of MPGN
Type 1 MPGN
Most common Type
Discrete immune deposits in the mesangium and subendothelial space, from circulating immune complexes, this causes mesangial proliferation and extension into the subendothelial zone.
Primary idiopathic MPGN is rare, and diagnosis of exclusion. Should be evaluated for chronic immune complex disease
Thickening of capillary walls,usually global and diffuse.
There is also hypercellularity. Much of this hypercellularity is mesangial proliferation, and some of the capillary wall thickening is caused by mesangial interposition into the subendothelial zone of the capillary loops
Type 2 (Dense Deposit disease)
15-35% of total MPGN cases
Characterized by a pathognomonic electron-dense transformation of GBMs and extensive complement deposition
Immunofluorescence is positive for C3 but negative for immunoglobulins
Recurs after renal transplant over 90% cases
Most have circulating IgG antibody (C3 nephritic factor) that stabilize C3bBb, C3 convertase of alternate pathway, resulted continuous C3 breakdown. – low C3
Higher hypocomplementemia and worse prognosis
Type 3 Mixed features of type I MPGN and membranous GN
Similar to type 1 but subepithelial deposits are prominent and complex disruption of the GBM
Inherited form of type 3 linked to chromosome 1q32
Idiopathic form occurs between ages of 8 and 30
In childhood, type I and II, frequently idiopathic or associated with nephritic factors
In adult, usually type I, commonly associated with cryoglobulinemia and HCV infection
Present with nephrotic range proteinuria or overt nephrotic syndrome, diffuse nephritis with hematuria, edema, hypertension and renal function impairment
Primary (idiopathic) vs. Secondary
Autoimmune disorders – SLE, Sjogren’s, Rheumatoid arthiritis, hereditary complement deficient state
Infections – chronic infections rather than acute; Hep B, Hep C, SBE, ventriculoatrial shunt infection, chronic visceral abscess, HIV, schistosomiasis, malaria, leprosy.
Thrombotic microangiopathies – transplant glomerulopathy, antiphospholipid antibody syndrome, TTP/HUS, scleroderma
Others – lipodystrophy, CLL, melanoma, alpha-1-antitrypsin deficiency, non-Hodgkin’s, renal cell carcinoma
Association with HIV in the absence of HCV not well known.