Membranous glomerulonephritis

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