Anti-GBM Disease

Question 1

Anti-glomerular basement membrane (Anti-GBM) disease is a rare small-vessel …

Answer 1

Anti-glomerular basement membrane (Anti-GBM) disease is a rare small-vessel vasculitis.

Question 2

Anti-GBM disease develops due to the formation of GBM antibodies directed against type … collagen.

Answer 2

Anti-GBM disease develops due to the formation of GBM antibodies directed against type IV collagen.

Question 3

Genetic risk - Anti-GBM disease

Answer 3

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.

Question 4

Anti-GBM disease is characterised by a rapidly progressive crescentic ….

Answer 4

Anti-GBM disease is characterised by a rapidly progressive crescentic glomerulonephritis.

Question 5

Anti-GBM disease is characterised by haematuria and pulmonary …

Answer 5

Anti-GBM disease is characterised by haematuria and pulmonary haemorrhage.

Question 6

Constitutional features - Anti-GBM disease

Like most systemic vasculitides, patients may develop preceding constitutional symptoms.

Answer 6

Lethargy
Fever
Anorexia
Weight loss
Myalgia
Arthralgia

Question 7

Approximately 90% of patients with anti-GBM disease present with a rapidly progressive glomerulonephritis, which is characterised by nephritic syndrome:

Answer 7

Oliguria/anuria: suggestive of acute kidney injury
Haematuria: visible or non-visible
Proteinuria: usually less marked than nephrotic syndrome
Hypertension

Question 8

Pulmonary manifestations

Pulmonary features of anti-GBM disease are more variable, observed in 25-60% of patients.

Answer 8

Cough
Shortness of breath
Haemoptysis
Pulmonary haemorrhage: may be seen in imaging

Question 9

Diagnosis of anti-GBM disease is made by identification of GBM antibodies in the serum or kidneys on …

Answer 9

Diagnosis of anti-GBM disease is made by identification of GBM antibodies in the serum or kidneys on biopsy.

Question 10

Anti-GBM antibodies have …

Answer 10

Anti-GBM antibodies have a high sensitivity (95-100%) and specificity (91-100%) for anti-GBM disease.

Question 11

Acute renal screen

Answer 11

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)

Question 12

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.

Answer 12

Light microscopy: shows evidence of glomerulonephritis with/without presence of crescents
Immunofluorescence: shows pathognomonic deposition of IgG anti-GBM antibodies on the basement membrane

Question 13

Pulmonary investigations

Anti GBM disease

Answer 13

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.

Question 14

Treatment of anti-GBM disease is with …, immunosuppressive agents and supportive measures.

Answer 14

Treatment of anti-GBM disease is with plasmapheresis, immunosuppressive agents and supportive measures.

Question 15

Plasmapheresis

Answer 15

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.

Question 16

Immunosuppression

Anti-GBM

Answer 16

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.

Question 17

Supportive renal measures

Answer 17

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.

Question 18

It is estimated that <…% of patients will require long-term dialysis following anti-GBM disease.

Answer 18

It is estimated that <30% of patients will require long-term dialysis following anti-GBM disease.

Question 19

anti-GBM disease prognosis

Answer 19

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.

Question 20

Supportive pulmonary measures

Anti-GBM disease

Answer 20

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