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INTRODUCTION
• Most recent version of the Chapel Hill nomenclature of vasculitis the
disease entity “Anti-glomerular basement membrane disease” (anti-
GBM-disease) is included among immune complex small vessel
vasculitides
• Second peak is in the sixth and seventh decades, and this later-onset
disease is more common in women, who more often have renal-limited
disease
1919—looking at pathologic
features of influenza in the lung
• 90% of anti–type IV collagen antibodies are directed against the α3-chain of type
IV collagen
• The alpha-3 chain forms a triple helix with alpha 4/5 chains,
combining with another triple helix to form a hexamer
• . The α-3 chain of type IV collagen is found predominantly in the GBM and
alveolar capillary basement membranes, which correlates with the limited
distribution of disease involvement in Goodpasture’s syndrome
• It is presumed that environmental factors, such as exposure to hydrocarbons,
tobacco smoke,and endogenous oxidants, can also expose the cryptic Goodpasture
epitopes
• Small percentage of patients with anti-GBM disease may also have limited
reactivity with the NC1 domains of the α1- or α4-chains of type IV collagen
• Mechanism by which some patients develop both anti-GBM antibodies and ANCAs
is unknown ANCAs may appear first and cause damage to the GBM, thus
exposing the normally hidden target epitopes of anti-GBM antibodies
• Mainly target two epitopes accessible in the α3α4α5 NC1 hexamers of human
GBM, unlike the sequestered α3 NC1 epitopes of anti-GBM autoantibodies.
Role of complements :
• Detailed analysis of the association with HLA-DR2 revealed a link with the DRB1
alleles, DRB1*1501 and DQB*0602
PATHOLOGY
LM
• 97% of patients with anti-GBM disease have some degree of crescent formation, and
85% have crescents in 50% or more of glomeruli
• Nonnecrotic segments may look entirely normal by light microscopy or may have
slight infiltration by neutrophils or mononuclear leukocytes.
• Kidney biopsy several weeks into the course of anti-GBM disease chronic
sclerotic lesions.
• Glomeruli with extensive necrosis and disruption of Bowman’s capsule typically have
intense periglomerular inflammation, including occasional multinucleated giant cells
• Discontinuous linear to granular capillary wall staining for C3, but a minority
show little or no C3 staining.
• Two other disorders in which linear IgG staining can be seen in the glomeruli:
diabetic nephropathy and fibrillary glomerulonephritis.
In the former and in the latter, the IgG is nonspecifically absorbed onto the
highly permeable glomerular capillary wall and onto the fibrils, respectively.
Acute disease focal glomerular necrosis with disruption of capillary walls. Bowman’s
capsule also may have focal gaps. Leukocytes, including neutrophils and monocytes,
often are present at sites of necrosis
• Patient survival of approximately 85% and renal survival of approximately 60% with
treatment
• Onset of disease may be associated with arthralgias, fever, myalgias, and abdominal
pain
• Serologic testing :
• High antibody titers are usually found in those with rapidly progressive disease.
• False negative results may occur in those with low antibody titers some patients with
Alport syndrome who develop posttransplant antiGBM disease, with antibodies
directed against the alpha5(IV) chain
• ELISA assays that use native or recombinant human alpha3(IV) antigen substrates
are much more sensitive and specific, sensitivity of 95 to 100 percent
and specificity of 91 to 100 percent
3. ANCA : 10 -38 percent of patients with antiGBM antibody disease also test positively
for ANCA (MPO- ANCA) at the time of diagnosis and may have signs of a systemic
vasculitis or a marked systemic inflammatory response
Low levels of ANCA may be detectable years before the production of antiGBM
antibodies and the onset of clinical symptoms
• The detection of ANCA is clinically relevant, as these patients may be more
likely to have treatable disease than those who have only antiGBM antibodies
TREATMENT
• Recovery is much more likely in patients who begin treatment before oliguria ensues,
Plasmapheresis :
The only available randomized trial evaluated outcomes among 17 patients who were
treated with prednisone and cyclophosphamide alone, or with plasmapheresis
End of treatment, two of eight patients who received plasmapheresis, compared with
six of nine in the immunosuppression alone group, became dialysis dependent
Johnson JP, Moore J Jr, Austin HA 3rd, et al. Therapy of antiglomerular basement membrane antibody disease: analysis of
prognostic significance of clinical, pathologic and treatment factors. Medicine (Baltimore) 1985; 64:219.
Bolton WK. Goodpasture's syndrome. Kidney Int 1996; 50:1753.
Madore F, Lazarus JM, Brady HR. Therapeutic plasma exchange in renal diseases. J Am Soc Nephrol 1996; 7:367.
• Patients with less than 30 percent crescents and a plasma creatinine below 3 mg/dL
did well, while those with severe crescentic involvement and a plasma creatinine
above 4 mg/dL (354micromol/L) did poorly
• Large retrospective study of 221 patients from China reported better patient and
renal survival among those treated with plasmapheresis, glucocorticoids, and
cyclophosphamide compared with those who received glucocorticoids and
cyclophosphamide
Cui Z, Zhao J, Jia XY, et al. Antiglomerular basement membrane disease: outcomes of different therapeutic
regimens in a large singlecenter Chinese cohort study. Medicine (Baltimore) 2011; 90:303.
• Daily or alternate day 4 liter exchanges for two to three weeks
• Recent renal biopsy or has pulmonary hemorrhage, then one to two liters of fresh
frozen plasma should be substituted for albumin at the end of the procedure to
reverse pheresis induced depletion of coagulation factors
• Continued pheresis may be required if the patient still has active pulmonary
disease (eg, hemoptysis) or if antibody titers are not declining substantially
Immunosuppressive therapy
DURATION OF THERAPY :
After remission is induced, maintenance therapy with less toxic drugs, such as lowdose
prednisone and azathioprine should be given for six to nine months.
AntiGBM antibody levels should be monitored every one to two weeks until they are
negative on two occasions
If the antiGBM antibody titers remain positive after three to four months of therapy
with cyclophosphamide, prednisone alone or in combination with azathioprine (1 to 2
mg/kg per day, which is substituted for cyclophosphamide) should be
continued for six to nine months.
Syeda UA, Singer NG, Magrey M. Antiglomerular basement membrane antibody disease treated with
rituximab: A casebased review. Semin Arthritis Rheum 2013; 42:567.
Long term outcomes with treatment : Based on a retrospective review of 71 patients
- patients with a plasma creatinine concentration of < 5.7 mg/dL ,patient and renal
survival were 100 and 95 percent at one year and 84 and 74 percent at last follow up
(median period of 90 months)
- patients who presented with a plasma creatinine concentration greater than 5.7
mg/dL but who did not require immediate dialysis (within 72 hours of presentation),
patient and renal survival were 83 and 82 percent at one year and 72 and 69 percent
at last follow up
- patients who required immediate dialysis, patient and renal survival were 65 and 8
percent at one year and 36 and 5 percent at last followup, respectively
Newer approaches : Immunoadsorption may be effective in antiGBM antibody
disease, even in dialysis dependent patients.
Combined use of immunosuppression and immunoadsorption using a sepharose-
coupled sheep antihuman IgG column for 25 cycles resulted in the recovery of
renal function, with a stable creatinine concentration of 2 mg/dL
KDIGO RECOMMENDATIONS