AntiGlomerular Basement Membrane Disease

Question 1

AntiGBM Disease

Epidemiology

Answer 1

Incidence: 0.5 to 0.9/million/year (predominantly Caucasians); rare in other ethnicities

Slight male predominance

Peak 20 to 30, and smaller peak at 60 to 70 years old

Question 2

AntiGBM Disease

Clinical Manifestations

Answer 2

Disease may develop over weeks to months.

May occur with mild respiratory symptoms or incidental microscopic hematuria with disease progressing over months to years

Question 3

AntiGBM Disease

Pathogenesis

Answer 3

Autoimmunity with antibody formation against the noncollagenous (NC1) domain of type IV collagen chain, α3(IV)NC1, a.k.a. the “Goodpasture antigen” or

Antibodies to any other GBM constituents, α3-α5(IV) chains

Question 4

AntiGBM Disease

Pathogenesis

Answer 4

These type IV collagen chains are also present in alveolus, cochlea, parts of eye (corneal basement membrane and Bruch membrane), choroid plexus of brain, and some endocrine organs, thus symptoms related to injury of these organs are also possible.

Question 5

AntiGBM Disease

Histopathology

Answer 5

LM: glomerular crescents without mesangial hypercellularity. Crescents are in the same stage (all active, all subacute, or all chronic) due to “one-shot” anti-GBM antibody production (in contrast to presence of crescents different stages with ANCA GN)

Question 6

AntiGBM Disease

Histopathology

Answer 6

IF: glomerular capillary wall IgG in a linear pattern

Question 7

AntiGBM Disease

Differential Diagnoses

Answer 7

Specific binding to GBM

Anti-GBM disease with kidney involvement only

Alport syndrome after renal transplantation

Nonspecific binding to GBM: diabetes mellitus (DM), light-chain disease, fibrillary GN, SLE

Question 8

AntiGBM Disease

Predisposing factors:

Answer 8

HLA-DR2: HLA-DRB1*1501

HLA-DR4: DRB1*1501 or DR4

DR1 and DR7 confer strong and dominant protection.

Question 9

AntiGBM Disease

Precipitating factors:

Answer 9

Underlying exposure to hydrocarbons, cigarette smoking, pulmonary infection, and fluid overload leads to an initial alveolar injury which allows the preformed anti-GBM antibodies to access and attack the alveolar membranes, thus leading pulmonary hemorrhage. Pulmonary hemorrhage may be seen on chest radiographs as “fluffy, fleeting infiltrates,” due to rapid onset and rapid clearing.

Question 10

AntiGBM Disease

Precipitating factors:

Answer 10

Prior kidney injury/inflammation may predispose the kidney to the development of anti-GBM disease. Again, the existing injury to the GBM allows anti-GBM antibodies access to the GBM to cause anti-GBM disease.

Question 11

AntiGBM Disease

Prognostic Indicators

Answer 11

Higher-presenting SCr and higher percentage of crescents portend worse prognosis.

Need for dialysis, particularly if in association with 100% crescents

Question 12

AntiGBM Disease

Management

Answer 12

Methylprednisolone 500 to 1,000 mg/d intravenously for 3 days, followed by prednisone, 1 mg/kg/d based on ideal body weight (maximum 80 mg/d) with slow taper to off by 6 months, plus

CYC: 3 mg/kg/d orally. For patients older than 55, reduce dose to 2.5 mg/kg/d × 2 to 3 months, plus

Question 13

AntiGBM Disease

Management

Answer 13

Plasmapheresis: one 4 L exchange daily with 5% albumin. Add 150 to 300 mL fresh-frozen plasma at the end of each session if patients have pulmonary hemorrhage, or have had recent surgery, including kidney biopsy. Plasmapheresis should be performed for 14 days or until anti-GBM antibodies become undetectable.

Question 14

AntiGBM Disease

Management

Answer 14

Maintenance immunosuppressive therapy for anti-GBM glomerulonephritis is not recommended. This disease is not characterized by frequently relapsing course. Antibodies tend to disappear spontaneously after 12 to 18 months.

Question 15

AntiGBM Disease

Management

Answer 15

Recurrence, if occurs, presents at a mean time of 4.3 years, range 1 to 10 years. Recurrence may manifest as kidney involvement or pulmonary hemorrhage. Treatment is similar to initial regimen outlined earlier.

Question 16

AntiGBM Disease

Management

Answer 16

Exception to immunosuppressive therapy initiation: patients who are dialysis-dependent at presentation and have 100% crescents in an adequate biopsy sample, and do not have pulmonary hemorrhage

Question 17

AntiGBM Disease

Management

Answer 17

Routine daily coagulation laboratory tests should be performed with additional FFP replacement as needed to correct any plasmapheresis-induced coagulopathy due to removal of coagulant factors.

Question 18

AntiGBM Disease

Management

Answer 18

Corticosteroids should be started prior to tissue diagnosis if high suspicion due to rapidly progressive disease. Following diagnosis confirmation, add CYC and plasmapheresis.

Question 19

AntiGBM Disease

Kidney Transplantation

Answer 19

Defer transplantation until anti-GBM antibodies are undetectable for at least 6 months.

Recurrent of disease is very unusual when transplant is performed six months or longer after antibody disappearance.

Question 20

AntiGBM Disease

Kidney Transplantation

Answer 20

New-onset anti-GBM disease following kidney transplantation should raise the possibility of Alport syndrome in the native kidneys.