Anti-GBM Disease Flashcards
Anti-glomerular basement membrane (Anti-GBM) disease is a rare small-vessel …
Anti-glomerular basement membrane (Anti-GBM) disease is a rare small-vessel vasculitis.
Anti-GBM disease develops due to the formation of GBM antibodies directed against type … collagen.
Anti-GBM disease develops due to the formation of GBM antibodies directed against type IV collagen.
Genetic risk - Anti-GBM disease
There is a strong genetic susceptibility linked to the presence of the human leucocyte antigen (HLA) DR15, which is found in >80% of patients. HLAs are involved in antigen processing and presentation as part of the immune response.
Anti-GBM disease is characterised by a rapidly progressive crescentic ….
Anti-GBM disease is characterised by a rapidly progressive crescentic glomerulonephritis.
Anti-GBM disease is characterised by haematuria and pulmonary …
Anti-GBM disease is characterised by haematuria and pulmonary haemorrhage.
Constitutional features - Anti-GBM disease
Like most systemic vasculitides, patients may develop preceding constitutional symptoms.
Lethargy Fever Anorexia Weight loss Myalgia Arthralgia
Approximately 90% of patients with anti-GBM disease present with a rapidly progressive glomerulonephritis, which is characterised by nephritic syndrome:
Oliguria/anuria: suggestive of acute kidney injury
Haematuria: visible or non-visible
Proteinuria: usually less marked than nephrotic syndrome
Hypertension
Pulmonary manifestations
Pulmonary features of anti-GBM disease are more variable, observed in 25-60% of patients.
Cough
Shortness of breath
Haemoptysis
Pulmonary haemorrhage: may be seen in imaging
Diagnosis of anti-GBM disease is made by identification of GBM antibodies in the serum or kidneys on …
Diagnosis of anti-GBM disease is made by identification of GBM antibodies in the serum or kidneys on biopsy.
Anti-GBM antibodies have …
Anti-GBM antibodies have a high sensitivity (95-100%) and specificity (91-100%) for anti-GBM disease.
Acute renal screen
An acute renal screen aims to determine the cause of any sudden deterioration in renal function. It is largely aimed at determining possible ‘intra-renal’ causes of acute kidney injury including glomerulonephritides.
Urinalysis: blood and protein suggestive of intra-renal cause.
Protein:creatinine ratio: quantify amount of proteinuria (e.g. is it ‘nephrotic’ range?)
Routine bloods: FBC, U&E, LFT, Bone, CK, Coagulation, CRP
Special bloods: ANA, ENA, dsDNA, ANCA, Anti-GBM, Protein electrophoresis, serum free light chains, complement, immunoglobulins, virology (hepatitis C, hepatitis B, human immunodeficiency virus +/- cytomegalovirus and epstein-barr virus), cryoglobulins.
Imaging: renal ultrasound +/- dopplers (to exclude obstruction, thrombus or stenosis)
Renal biopsy
A biopsy of one of the kidneys should be completed in suspected anti-GBM disease unless contraindicated. The sample can be assessed with light microscopy and under immunofluorescence.
Light microscopy: shows evidence of glomerulonephritis with/without presence of crescents
Immunofluorescence: shows pathognomonic deposition of IgG anti-GBM antibodies on the basement membrane
Pulmonary investigations
Anti GBM disease
Chest radiograph +/- computed tomography can be used to assess the lungs in patients with suspected anti-GBM disease. In patients with massive pulmonary haemorrhage, pulmonary angiography with embolisation may be required.
Pulmonary function tests are usually not required but will show a raised diffusing capacity for carbon monoxide (DLCO) due to haemorrhage and carbon monoxide binding.
Treatment of anti-GBM disease is with …, immunosuppressive agents and supportive measures.
Treatment of anti-GBM disease is with plasmapheresis, immunosuppressive agents and supportive measures.
Plasmapheresis
Plasmapheresis is the process of removing a patients plasma from the body and replacing it with another solution such as human albumin. In anti-GBM disease, it is utilised to remove circulating autoantibodies and other inflammatory mediators.
Plasmapheresis can continue for 2-3 weeks and a set protocol should be followed in most cases.
Immunosuppression
Anti-GBM
The use of immunosuppressive agents should be combined with plasmapheresis. The choice of agent includes steroids combined with cyclophosphamide. Again, a set protocol will be used to decide on the dose and timing of administration.
Cyclophosphamide is traditionally an alkylating chemotherapeutic agent, which has been widely shown to improve outcomes in systemic inflammatory conditions such as anti-GBM disease and ANCA-vasculitis.
Generally, if remission is achieved then maintenance immunosuppression does not need to be continued.
Supportive renal measures
In patients with severe acute kidney injury (AKI), temporary initiation of haemodialysis may be required. The indications to start dialysis remain the same as any other cause of severe AKI.
With the aggressive use of immunosuppressive agents patients should be able to come off dialysis. However, a proportion of patients will end up with established end-stage renal disease and ongoing need for dialysis.
It is estimated that <…% of patients will require long-term dialysis following anti-GBM disease.
It is estimated that <30% of patients will require long-term dialysis following anti-GBM disease.
anti-GBM disease prognosis
It is estimated that <30% of patients will require long-term dialysis following anti-GBM disease.
Patients may be extremely unwell on presentation and develop complications secondary to renal impairment (e.g. hyperkalaemia, acidosis), or pulmonary involvement (e.g. massive haemorrhage).
With the instigation of aggressive early treatment, the overall prognosis has greatly improved and 5-year survival exceeds 80%. Patients require ongoing monitoring to assess for renal recovery or need to continue haemodialysis.
Supportive pulmonary measures
Anti-GBM disease
Patients with life-threatening pulmonary haemorrhage may require intubation and ventilation. This can be combined with measures to control bleeding including bronchoscopy or angiography and embolisation
