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AntiGBM Antibody Crescentic Glomerulonephritis' AM Report Paul Ossman


Acute renal failure with nephrotic range proteinuria. Nephritic sediment: dysmorphic red cells, white cells, ... ELISA with confirmatory Western blot testing ... – PowerPoint PPT presentation

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Title: AntiGBM Antibody Crescentic Glomerulonephritis' AM Report Paul Ossman

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Anti-GBM Antibody Crescentic Glomerulonephritis. A
M Report Paul Ossman
Presentation of Anti-GBM Glomerulonephritis
  • Acute renal failure with nephrotic range
  • Nephritic sediment dysmorphic red cells, white
    cells, and red cell and granular casts.
  • In 60 to 70 percent of patients , there is
    pulmonary involvement
  • alveolar hemorrhage
  • shortness of breath
  • cough, sometimes overt hemoptysis and even iron
    deficiency anemia
  • pulmonary infiltrates on chest x-ray
  • increased carbon monoxide diffusing capacity

Ernest Goodpasture
  • American pathologist
  • In 1919, Dr. Goodpasture described the first
    report of renal insufficiency with pulmonary
    involvement which would later be classified as
    Anti-GBM antibody disease .
  • One of the three major forms of rapidly
    progressive glomerulonephritis with crescentic

  • Circulating Anti-GBM antibody are directed
    against the NC1 domain of the alpha-3 chain of
    type IV collagen (highly expressed in the
    glomerular basement membrane and alveoli)
  • results in acute or rapidly progressive
  • typically associated with crescent formation
  • typically presents with the syndrome of
    glomerulonephritis and pulmonary hemorrhage
  • may present with glomerulonephritis alone

Crescentic Glomerulonephritis
  • Production of anti-GBM antibodies is short-lived,
  • Unknown stimulus
  • Typically IgG but sometimes IgA or IgM
  • Antibodies represent about 1 percent of the
    circulating IgG.
  • Binding to the GBM is rapid and tight.

Pulmonary Involvement
  • Circulating anti-GBM antibodies must have access
    to the alveolar basement membrane to do damage.
  • Underlying pulmonary injury
  • Smoking
  • Infection
  • Cocaine inhalation
  • Hydrocarbon exposure

Diagnosis Anti-GBM antibodies either in the
serum or the kidney.
  • Renal biopsy
  • Crescentic glomerulonephritis
  • Linear deposition of IgG along the glomerular
  • Serologic testing for anti-GBM antibodies.
  • ELISA with confirmatory Western blot testing
  • ANCA - Between 10 and 38 percent of patients with
    anti-GBM antibody disease also test positively
    for ANCA

Treatment of Choice
  • Early diagnosis and treatment
  • Plasmapheresis Prednisone Cyclophosphamide
  • Plasmapheresis removes circulating anti-GBM
    antibodies and other mediators of inflammation
    (such as complement),
  • immunosuppressive agents minimize new antibody

Little Randomized Evidence
  • Plasmapheresis is associated with improved
    morbidity and mortality compared to historic
    rates prior to plasmapheresis.
  • Biological plausibility of improved outcomes with
    rapid removal of anti-GBM antibody, compared with
    a slower reduction in levels seen with
    immunosuppressive agents alone.

How Much and How Long?
  • Daily or alternate day 4-liter exchanges for two
    to three weeks
  • If there is a marked decline in serum anti-GBM
    antibody titers after initial treatment, further
    plasmapheresis may be unnecessary
  • Pulse methylprednisolone 15 to 30 mg/kg to a
    maximum of dose of 1000 mg intravenously over 20
    minutes daily for three doses
  • Then, oral prednisone at 1 mg/kg per day to a
    maximum of 60 to 80 mg/day
  • Then, prednisone is tapered once remission is
  • Cyclophosphamide dose is 2 mg/kg per day orally,
    but not exceed 100 mg per day in patients over
    the age of 60 years to limit toxicity.

Survival and Relapse
  • Those who survive the first year with intact
    renal function generally do well.
  • Relapses are uncommon 2
  • Smokers and those who have had exposure to
    hydrocarbons have a higher rate of recurrence

Treatment Response
  • Best candidates
  • Patients with very acute disease (ireversible
    injury is less predictable)
  • Younger patients (better able to tolerate
    aggressive immunosuppression)
  • Anti-GBM antibody disease ANCA clinical signs
    of a systemic vasculitis
  • As many as 40 percent of such patients recover
    some function if they are also ANCA positive.

  • If acute glomerulonephritis is untreated ,
    prognosis is extremely poor
  • Death or dialysis has been estimated to be as
    high as 90 percent
  • Direct correlation between plasma creatinine the
    percent of glomeruli with crescents
  • Crescents are present in more than 75 percent of
    glomeruli when the plasma creatinine
    concentration is above 5 mg/dL
  • The proportion of preserved glomeruli may be the
    best determinant of prognosis

  • If treated
  • 40 to 45 percent of patients will benefit by not
    progressing to end-stage renal disease or death
  • Recovery is more likely when treatment begins
    before oliguria.
  • However, in those who require dialysis or who
    have 75 - 100 percent crescents on biopsy,
    recovery is rare regardless of treatment.

  • Bolton, WK. Goodpasture's syndrome. Kidney Int
    1996 501753.
  • Jennette, JC. Rapidly progressive crescentic
    glomerulonephritis. Kidney Int 2003 631164.
  • Levy, JB, Turner, AN, Rees, AJ, Pusey, CD.
    Long-term outcome of anti-glomerular basement
    membrane antibody disease treated with plasma
    exchange and immunosuppression. Ann Intern Med
    2001 1341033
  • Pusey, CD. Anti-glomerular basement membrane
    disease. Kidney Int 2003 641535.
  • Up To Date