History and exam

Key diagnostic factors

common

reduced urine output

Possible renal insufficiency.[3]​

hemoptysis

Occurs in 60% of patients.[3]

edema

Occurs in 34% of patients.[3]

Other diagnostic factors

common

male gender

Mild male predominance of 60% male, 40% female.[3]

age 20 to 30 years or 60 to 70 years

Bimodal age distribution with peak incidence at 20 to 30 years and then at 60 to 70 years.[3]

shortness of breath

Shortness of breath, cough, and fever occur in 28% of patients.[3]

cough

Shortness of breath, cough, and fever occur in 28% of patients.[3]

fever

Shortness of breath, cough, and fever occur in 28% of patients.[3]

nausea

Occurs in 20% of patients.[3]

crackles on lung examination

Occurs in 46% of patients.[3]

Risk factors

strong

HLA-DRB1 or DR4

More than 90% of patients have HLA-DRB1*1501 or HLA-DR4.[8]

smoking

The development of pulmonary hemorrhage is strongly correlated with cigarette smoking.[7][14]​ In patients with anti-glomerular basement membrane (anti-GBM) disease, nonspecific lung injury predisposes patients to pulmonary involvement.[6][14]​​

weak

exposure to hydrocarbons, organic solvents, heavy metals

Limited anecdotal evidence suggests exposure to hydrocarbons, organic solvents and heavy metals may be associated with an increased risk of developing anti-GBM disease.[15][16]

history of lithotripsy

A small number of case reports have identified extracorporeal shock wave lithotripsy as a potential trigger for clinical anti-GBM disease in genetically susceptible individuals.[17]​ The pathophysiology of this rare phenomenon remains unclear but a suggested mechanism is that the procedure may expose epitopes within the glomerular basement membrane (GBM), triggering the formation of anti-GBM antibodies.[17]

recent respiratory infections

Respiratory infections may trigger pulmonary involvement in those with circulating anti-GBM antibodies, due to nonspecific lung injury.[18][19]

There are some reports of anti-GBM disease occurring among individuals following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections.[20]

immunotherapy

Renal limited anti-GBM disease has been reported among patients receiving alemtuzumab for the treatment of multiple sclerosis.[21][22]

Anti-GBM disease has also been associated with immune checkpoint inhibitors. These drugs may cause atypical disease, in that patients did not have detectable circulating anti-GBM antibodies.[23]

Tumor necrosis factor (TNF)-alpha inhibitors have also been implicated.[24]

post-renal transplant in patients with Alport syndrome

Anti-GBM disease is a rare but devastating complication occurring in renal allografts of patients with Alport syndrome. The incidence is about 3% to 5% and is more common in males with X-linked disease.[25]​ The primary pathology in Alport syndrome is a defect in the COL4A5 collagen chain (sometimes in the A3 or A4 chain), leading to an abnormal GBM. Upon transplant, alloantibodies are generated against the allograft GBM, leading to anti-GBM disease.[26]

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