Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

suspected rapidly progressive glomerulonephritis

1st line – oral corticosteroid

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INITIAL
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suspected rapidly progressive glomerulonephritis
1st line – 

oral corticosteroid

If it is known that a definitive diagnosis will be delayed beyond 24 hours due to an inability to perform renal biopsy or other diagnostic testing, the safest presumptive therapy (i.e., a corticosteroid plus plasma exchange) should be initiated with a plan to perform a diagnostic biopsy the next day.[1]

Primary options

prednisolone: 1 mg/kg/day orally

Plus – plasma exchange

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INITIAL
|
suspected rapidly progressive glomerulonephritis
Plus – 

plasma exchange

Treatment recommended for ALL patients in selected patient group

Plasma exchange of 1 to 1.5 times a patient's total plasma volume daily for 2-3 weeks, or until anti-glomerular basement membrane (anti-GBM) titres are undetectable.[28][29]​​​ The purpose of this treatment is to remove the pathogenic antibody. FBC and clotting parameters must be monitored on a daily basis.

If bleeding occurs, clotting factors may need to be replaced with fresh frozen plasma.

Plus – supportive measures and cessation of exposure to cigarette smoke

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INITIAL
|
suspected rapidly progressive glomerulonephritis
|
with pulmonary haemorrhage at presentation
Plus – 

supportive measures and cessation of exposure to cigarette smoke

Treatment recommended for ALL patients in selected patient group

Supplemental oxygen or intubation may be needed but should be managed as far as possible to avoid hyperoxia and infection, both of which may also exacerbate pulmonary haemorrhage.[33]

Cryoprecipitate and fresh frozen plasma may be required if coagulopathy develops.

Patients should be advised to stop smoking.

ACUTE

reversible renal disease or any pulmonary involvement

1st line – oral corticosteroid

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ACUTE
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reversible renal disease or any pulmonary involvement
1st line – 

oral corticosteroid

Treatment for this patient group involves a combination of high-dose corticosteroids, cyclophosphamide, and plasma exchange.

Prophylaxis against osteoporosis, gastritis, and pneumocystis pneumonia should be considered during long-term high-dose corticosteroid therapy.

Primary options

prednisolone: 1 mg/kg/day orally initially, then taper dose gradually over 6-9 months, maximum 60 mg/day

Plus – cyclophosphamide or mycophenolate or rituximab

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ACUTE
|
reversible renal disease or any pulmonary involvement
Plus – 

cyclophosphamide or mycophenolate or rituximab

Treatment recommended for ALL patients in selected patient group

Treatment with cyclophosphamide (or an alternative immunosuppressant) might be best reserved until biopsy results are available to confirm the diagnosis.

Renal biopsy findings that would favour aggressive treatment are fresh cellular crescents with little scarring, indicating a very acute process, or many preserved glomeruli with a second 'reversible' injury that might account for the severity of renal failure, such as acute tubular injury.

Conversely, if most glomeruli show crescents (85% to 100%) or if >50% glomeruli have global glomerulosclerosis, the prospects for renal recovery are much reduced, thereby favouring early discontinuation of immunosuppression (for renal disease), unless patients also present with pulmonary haemorrhage.[29]

The treatment course with cyclophosphamide is generally 2 to 3 months. Adverse effects may include neutropenia, haemorrhagic cystitis, bladder cancer, and gonadal toxicity. Consider preservation of gametes and pneumocystis prophylaxis. Monitor WBC count weekly. Dose should be reduced for older patients (>60 years) or in those with renal impairment, especially if dialysis dependent at the time of initiation of treatment.

Intravenous cyclophosphamide may be considered for patients who are intolerant to oral cyclophosphamide or if there are concerns for compliance. Consider mycophenolate or rituximab in patients who are unable to tolerate cyclophosphamide.[29]​ Adverse effects of mycophenolate may include gastrointestinal disturbances and insomnia; adverse effects of rituximab may include infusion reactions.

Initial therapy for patients with positive anti-neutrophil cytoplasmic antibody (ANCA) is identical to initial treatment for patients without ANCA. If a patient treated with cyclophosphamide remains ANCA-positive after an initial treatment period of three months, they should be switched from cyclophosphamide to maintenance therapy (corticosteroid and immunomodulatory therapy) as for other ANCA-positive diseases.

Primary options

cyclophosphamide: 2-3 mg/kg orally once daily for 2-3 months; consult specialist for guidance on intravenous dose

Secondary options

mycophenolate mofetil: consult specialist for guidance on dose

OR

rituximab: consult specialist for guidance on dose

Plus – plasma exchange

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ACUTE
|
reversible renal disease or any pulmonary involvement
Plus – 

plasma exchange

Treatment recommended for ALL patients in selected patient group

Plasma exchange of 1 to 1.5 times a patient's total plasma volume daily for 2-3 weeks, or until anti-GBM titres are undetectable.[28][29]​​​​

The purpose of this treatment is to remove the pathogenic antibody. FBC and clotting parameters must be monitored on a daily basis.

If bleeding occurs, clotting factors may need to be replaced with fresh frozen plasma.

irreversible renal disease and no evidence of pulmonary involvement

1st line – supportive care alone

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ACUTE
|
irreversible renal disease and no evidence of pulmonary involvement
1st line – 

supportive care alone

Aggressive treatment (plasma exchange, cyclophosphamide, and corticosteroids) may be withheld if kidney function is unlikely to recover and the patient has no pulmonary symptoms.

Kidney function is unlikely to recover if dialysis is needed at presentation, initial creatinine is ≥0.3 mmol/L (≥5.7 mg/dL), and kidney biopsy shows 100% crescents or >50% glomerulosclerosis.[28][29]​​​[32]

The low likelihood of renal recovery in these patients (<10%) means the risks of aggressive treatment could outweigh the potential benefits.[32][34][35]​​ Treatment decisions must, therefore, be highly individualised, taking into account reversibility on renal biopsy and any comorbid conditions. Supportive care alone is often appropriate.[1]

Factors favouring aggressive treatment are fresh cellular crescents with little scarring, indicating a very acute process, or many preserved glomeruli with a second possible 'reversible' injury that might account for the severity of renal failure (e.g., acute tubular injury).[29]

Patients should be advised to stop smoking.

ONGOING

unresponsive to initial treatment

1st line – alternative immunosuppressant

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ONGOING
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unresponsive to initial treatment
1st line – 

alternative immunosuppressant

Where anti-GBM antibodies are persistently positive following a three-month course of cyclophosphamide, use of rituximab, azathioprine, or mycophenolate can be considered.[29]

Decisions on further immunosuppressant treatment should be made on a case by case basis, and depend on the clinical status and initial pathology of the patient.

Adverse effects of rituximab may include infusion reactions. Adverse effects of azathioprine may include pancreatitis and transaminitis. Adverse effects of mycophenolate may include gastrointestinal disturbances and insomnia.

Primary options

rituximab: consult specialist for guidance on dose

OR

azathioprine: consult specialist for guidance on dose

OR

mycophenolate mofetil: consult specialist for guidance on dose

Plus – continue oral corticosteroid

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ONGOING
|
unresponsive to initial treatment
Plus – 

continue oral corticosteroid

Treatment recommended for ALL patients in selected patient group

Prophylaxis against osteoporosis, gastritis, and pneumocystis pneumonia should be considered during long-term high-dose corticosteroid therapy.

Primary options

prednisolone: 1 mg/kg/day orally initially, then taper dose gradually over 6-9 months, maximum 60 mg/day

Consider – plasma exchange

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ONGOING
|
unresponsive to initial treatment
Consider – 

plasma exchange

Additional treatment recommended for SOME patients in selected patient group

If anti-GBM titres are detectable, consider plasma exchange of 1 to 1.5 times a patient's total plasma volume for 2-3 weeks or until titres are undetectable.[28][29]​​​​​

The purpose of this treatment is to remove the pathogenic antibody. FBC and clotting parameters must be monitored on a daily basis.

If bleeding occurs, clotting factors may need to be replaced with fresh frozen plasma.

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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