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Membranous Glomerulonephritis
Membranous nephropathy
BY- AKALYA ATPUTHANANTHAN ABUL KALAM AZAD
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.
NOTE- Membranoproliferative glomerulonephritis involves the basement membrane and mesangium, while membranous glomerulonephritis involves the basement membrane but not the mesangium
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.
Membranoproliferative glomerulonephritis involves the basement membrane and mesangium, while membranous glomerulonephritis involves the basement membrane but not the mesangium
Morphology
LM: Diffuse thickening of the GBM EM: Subepithelial deposits (“Spike & dome” pattern) Effacement of foot processes Immunofluorescence microscopy:
Granular deposits
Normal Glomerulus thin GBM (equivalent
to tubular basement membrane)
mesangium limited to stalk of capillary tuft (double arrows)
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
DX
URINE ANALYSIS
BIOPSY IS GOLD STANDARD
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.
Month 1: IV methylprednisolone (1 g) daily for 3 doses, then oral methylprednisolone (0.5 mg/kg/d) for 27 days
Month 2: Oral chlorambucil (0.15–0.2 mg/kg/d) or oral cyclophosphamide (2 mg/kg/d) for 30 days Month 3: Repeat month 1 Month 4: Repeat month 2 Month 5: Repeat month 1 Month 6: Repeat month 2
Monitor every 2 weeks for 2 months, then every month for 6 months, with serum creatinine, urinary protein excretion, serum albumin, and white blood cell count. If total leukocyte count falls to less than 3500/µL, hold chlorambucil or cyclophosphamide until recovery to 44000/µL
Ponticelli regimen
Treatment: Low Risk
ACE I or ARB: act, at least in part, to lower intraglomerular pressure
Goal BP <130/80 may require diuretics
Lipid-lowering: statins most often needed low salt diet anticoagulation: controversial
highest risk: >12 g/day, albumin <2
Treatment: Moderate and High Risk
Moderate: 4-8 g/day x 6 months (45% will have spontaneous remission) if no better in 6 mos: immunosuppression
High: > 8 g/day x 6 months or worsening renal function (75% progress to ESRD)
cyclophosphamide OR cyclosporine/tacrolimus PLUS glucocorticoidsCyclosporine: 3.5–5.0 mg/kg/d given orally in 2 equally divided doses 12 hours apart, with prednisone 0.15 mg/kg/d, for 6 monthsTacrolimus: 0.05–0.075 mg/kg/d given orally in 2 divided doses 12 hours apart, without prednisone, for 6–12 months; levels should be monitored
trial of rituximab Transplant: if ESRD – 10-30% recurrence
Prognosis
1/3 have spontaneous remission,
1/3 progress to require dialysis and
1/3 continue to have proteinuria, without progression of renal failure.
THANK YOU FOR YOUR ATTENTION
