Membranoproliferative Glomerulonephritis (MPGN)

• Type I - Chronic Immune Complex GN

• Granular deposits of IgG and C3 in subendothelial and mesangial distributions

• Activation of classic complement pathway

• Presence of cryoglobulins and circulating Igs

• Similar lesions produced in animal studies utilizing foreign serum proteins

• Type II – Dense deposit disease

• NOT an immune complex disease

• Probably due to abnormality in complement metabolism

• C3 nephritic factor present in the serum

• Type I
• Light Microscopy
• Diffuse, proliferative GN
• Thickening of glomerular capillary walls due to subendothelial immune deposits and interposition of mesangial matrix and cells between layers of GBM
• Seen on silver stain as double contour, splitting, or train track appearance of capillary walls.
• Increase in mesangial cells and matrix
• Glomerulus appears lobulated
• Crescents rare
• Immuno Fluorescence – Coarsely granular deposits of C3 and often IgG, IgM, C4, properdin, and fibrin in mesangium and peripheral capillary loops
• Electron Microscopy
• Dense subendothelial and mesangial deposits
• Mesangial matrix interposition w/ capillary wall thickening and narrowing of capillary lumen
  

• Type II
• LM
• Similar to Type I, although crescents are more common
• Dense deposits seen as PAS+, ribbon-like deposits w/in the capillary wall (i.e., intamembranous) as well as along Bowman’s capsule and tubular membrane.
• IF – C3 present in deposits, IgG much less commonly found
• EM – extensive replacement of lamina densa with “very dense deposits”

Know the clinical manifestations and prognosis of MPGN

• Mainly a disease of children/young adults
• Exception – association of type I with Hepatitis B infection
• Nephrotic Syndrome (80%)
• Acute nephritic syndrome (20%) more common in type I
• Type II associated with partial lipodystrophy in some patients
• Poor prognostic signs include
• Reduced GFR at onset
• Presence of nephrotic syndrome
• Early HTN
• Gross hematuria
• Presence of crescents or sclerosis on biopsy
• Recurs in about 25% of transplants, but rarely interferes with function

Know the urinary sediment and renal function of MPGN

• Shows nephrotic range proteinuria along with nephritic syndromes such as hematuria

• About 33% develop end-stage renal disease w/in 10 years (type II) or 15-20 years (type I)

• About 33% have persistent nephrotic syndrome with relatively stable renal function

• About 33% have persistent non-nephrotic proteinuria and/or hematuria

• Less than 5% experience spontaneous remission

Category: Pathology Notes