membranous glomerulonephritis
DESCRIPTION
TRANSCRIPT
Membranous Glomerulopathy
Membranous Glomerulonephritis
Membranous nephropathy
Membranous nephritis Lecture 42
Membranous GN
• This is a slowly progressive disease,• most common between 30 & 50 years of age• Usually caucasian. • Well developed cases show diffuse thickening of the capillary
wall.
Membranous Glomerulonephritis
• It is the second most common cause of nephrotic syndrome in adults, with focal segmental glomerulosclerosis (FSGS) being the most common.
Types: Primary & Secondary
Primary/idiopathic
85% of MGN cases are classified as
primary membranous glomerulonephritis—that is to say, the cause of the disease is idiopathic (of unknown origin or cause). This can also be referred to as idiopathic membranous nephropathy.
Secondary MGNThe remainder (15%) is secondary due to:1.autoimmune conditions (e.g.,
systemic lupus erythematosus)2. infections (e.g., syphilis, malaria, hepatitis B)3.drugs (e.g., captopril, NSAIDs, penicillamine,
probenecid).4.inorganic salts (e.g. gold, mercury).5.tumors, frequently solid tumors of the lung and
colon.
Pathogenesis• MGN is caused by immune complex formation
in the glomerulus. The immune complexes are formed by binding of antibodies to antigens in the glomerular basement membrane.
• The antigens may be part of the basement membrane, or deposited from elsewhere by the systemic circulation.
Pathogenesis• The immune complex serves as an activator
that triggers a response from the C5b - C9 complements, which form a
membrane attack
complex (MAC) on the glomerular epithelial cells.
Pathogenesis
• MAC, in turn, stimulates release of
proteases and oxidants by the mesangial and epithelial cells, damaging the capillary walls and causing them to become "leaky".
Pathogenesis
• In addition, the epithelial cells also
seem to secrete an unknown
mediator that reduces nephrin synthesis and distribution.
Morphology• LM: Diffuse thickening of the GBM• EM: Subepithelial deposits (“Spike & dome”
pattern)• Effacement of foot processes• Immunofluorescence microscopy:
Granular deposits
LM: The capillary loops are thickened and prominent, but the cellularity is not increased.
Clinical Presentation
• Some patients may present as nephrotic syndrome with proteinuria, edema with or without renal failure.
• Others may be asymptomatic and may be picked up on screening or urinalysis as having proteinuria.
• A definitive diagnosis of membranous nephropathy requires a kidney biopsy.
Clinical Course• Nephrotic syndrome• Nonselective proteinuria• Does not respond to corticosteroids• Variable & Indolent course
Treatment• Treatment of secondary membranous
nephropathy is guided by the treatment of the original disease.
• For treatment of idiopathic membranous nephropathy, the treatment options include immunosuppressive drugs and non-specific anti-proteinuric measures.
Prognosis•1/3 have spontaneous remission,
•1/3 progress to require dialysis and
•1/3 continue to have proteinuria, without progression of renal failure.
