Membranoproliferative Glomerulonephritis (MPGN)

Mesangiocapillary glomerulonephritis

Epidemiology and Etiology:

· Children and young adults

· Idiopathic (primary)

· Type I

· Immune complexes, antigens unknown (?infectious agents

· Type II (Dense-deposit disease)

· Deposits are of unknown composition

· Abnormal activation of alternative complement pathway

· Secondary (invariably type I)

· Chronic immune complex disorders

· SLE

· Hepatitis B

· Hepatitis C

· Cryoglobulinemia

· Endocarditis

· Infected ventriculoatrial shunts

· Chronic visceral abscesses

· HIV infection

· Schistosomiasis

· Alpha-1-antitrypsin deficiency

· Malignancies

· CLL

· Lymphoma

· Hereditary complement deficiencies

Common sites:

·

Gross features:

·

Histologic features:

· Large hypercellular glomeruli

· Alterations in basement membrane

· Thickened, often focally

· “double-contour” or “tram-track” appearance of glomerular capillary wall

· Silver or PAS stains show them better

· Inclusion or interposition of cellular elements

· Mesangial, endothelial, leukocytic

· Proliferation of glomerular cells

· Mesangial cells

· Capillary endothelial cells

· Leukocyte infiltration

· Increased mesangial matrix

· Parietal epithelial crescents often

Immunophenotype:

Marker:

Sensitivity:

Specificity:

·  Type I:

· C3 deposited in a granular pattern

· IgG and early complement components (C1q and C4) often also present

· Type II:

· C3 in irregular granular or linear foci in the basement membrane (but not in dense deposits themselves)

· C3 in mesangium in characteristic circular aggregates (mesangial rings)

· IgG absent usually

· C1q and C4 absent usually

Molecular features:

·

Other features:

· Nephrotic syndrome

· Or combined nephrotic-nephritic syndrome

· Slowly progressive and unremitting course

· CRF within 10y (50%)

· Some RPGN

· High incidence of recurrence in transplant recipients, particularly type II

· EM:

· Duplication of basement membrane

· Type I:

· Subendothelial electron-dense deposits

· Mesangial and occasional subepithelial deposits maybe

· Type II (dense-deposit disease):

· Lamina densa is irregular, ribbon-like, extremely electron-dense

· Serum:

· Type II:

· C3 nephritic factor (C3NeF) (circulating antibody) (70%)

· Autoantibody that binds to C3 convertase

References:

· Kumar V, Fausto N, Abbas A. Robbins & Cotran Pathologic Basis of Disease, Seventh Edition. 7th ed. Saunders; 2004.