Pulmonary Renal Syndrome

Pulmonary renal syndrome is the combination of diffuse alveolar haemorrhage and glomerulonephritis, usually rapidly progressive. It is a life threatening emergency with mortality of 25 to 50% from respiratory failure or kidney failure.

The commonest cause is ANCA-associated vasculitis (microscopic polyangiitis and granulomatosis with polyangiitis, 60 to 70%), followed by anti-GBM disease (Goodpasture disease), systemic lupus erythematosus, cryoglobulinaemic vasculitis, IgA vasculitis, Behçet disease, antiphospholipid syndrome, and drugs (propylthiouracil, hydralazine, levamisole contaminated cocaine).

Mimics include pulmonary oedema with acute kidney injury, severe pneumonia with sepsis (Legionella, leptospirosis, hantavirus), uraemic lung, and pulmonary embolism.

Pathophysiology. Immune mediated injury of alveolar and glomerular capillaries (neutrophil activation by ANCA, anti-GBM antibody binding to the alpha-3 chain of type IV collagen common to both basement membranes, or immune complexes) causes capillaritis, necrosis and haemorrhage.

• Haemoptysis (absent in about one third), dyspnoea, cough, hypoxia, chest pain, fever.
• Kidney: haematuria, proteinuria, rising creatinine, oliguria, hypertension.
• Systemic features: sinusitis, epistaxis, saddle nose, ear disease, purpura, arthralgia, uveitis, mononeuritis multiplex, malar rash, oral ulcers, livedo.
• Falling haemoglobin, bilateral infiltrates, tachypnoea.

Red flags

• Respiratory rate above 30/min, oxygen saturation below 92% on air, or need for ventilation.
• Haemoglobin falling by 20 g/L or more within 24 to 48 hours.
• Creatinine above 300 micromol/L or oliguria.
• Massive haemoptysis (over 200 mL in 24 hours).

• Urgent: arterial blood gas, full blood count (anaemia, neutrophilia, thrombocytosis), CRP, creatinine and electrolytes, coagulation, urinalysis with microscopy, ECG.
• Serology (same day): ANCA (PR3 and MPO), anti-GBM antibody, antinuclear antibody, anti-dsDNA, complement, antiphospholipid antibodies, cryoglobulins, hepatitis B and C, HIV; blood and sputum cultures, Legionella and pneumococcal urinary antigens, leptospirosis serology.
• Imaging: chest radiograph and CT (bilateral ground glass or consolidation, sparing the periphery); echocardiography to exclude cardiogenic oedema.
• Bronchoscopy with lavage: progressively bloodier aliquots and haemosiderin laden macrophages confirm alveolar haemorrhage and exclude infection (aim before immunosuppression, if safe).
• Pulmonary function: raised diffusing capacity for carbon monoxide (if able).
• Kidney biopsy as soon as possible (crescentic glomerulonephritis; immunofluorescence differentiates anti-GBM, pauci-immune and immune complex disease).

Differential diagnosis

• Cardiogenic pulmonary oedema, bacterial or viral pneumonia, pulmonary embolism, acute respiratory distress syndrome with acute kidney injury, uraemic lung, drug toxicity (amiodarone, methotrexate, cocaine), leptospirosis, hantavirus, malignancy, tuberculosis.

Resuscitation and organ support

• High dependency or intensive care. Oxygen to saturation 94 to 98%; non-invasive or invasive ventilation with lung protective settings (tidal volume 6 mL/kg, plateau pressure under 30 cmH2O) and high positive end expiratory pressure for haemorrhage; extracorporeal membrane oxygenation for refractory hypoxaemia.
• Transfuse to haemoglobin above 70 g/L; correct coagulopathy; avoid fluid overload; dialysis for refractory hyperkalaemia above 6.5 mmol/L, pH under 7.15, overload or uraemic complications.
• Treat any coexisting infection (empirical antibiotics until cultures are available).

Immunosuppression (start immediately; do not wait for serology if clinically probable)

• Methylprednisolone 500 mg to 1 g intravenously daily for 3 days, then prednisolone 1 mg/kg daily (maximum 60 mg), reduced to 20 mg by week 6.
• Plus cyclophosphamide 15 mg/kg intravenously (maximum 1.2 g; 12.5 mg/kg at age 60 to 70 and 10 mg/kg over age 70) every 2 weeks for 3 doses, then every 3 weeks, or rituximab 375 mg/m² weekly for 4 doses (or 1 g on days 1 and 15).
• Plasma exchange (60 mL/kg, 7 exchanges over 14 days; daily for 14 days with 50 mL/kg of 4% albumin in anti-GBM disease) for diffuse alveolar haemorrhage, anti-GBM or double positive disease.
• Cause specific: lupus, treat with steroid, cyclophosphamide and hydroxychloroquine 200 mg daily; antiphospholipid syndrome, anticoagulation and immunosuppression; drug induced, stop the offending drug.
• Co-trimoxazole 480 mg daily for pneumocystis prophylaxis; proton pump inhibitor.

Maintenance. After remission, rituximab 500 mg every 6 months for 18 months or azathioprine 2 mg/kg daily for ANCA disease; avacopan 30 mg twice daily is an option as a steroid sparing agent. Anti-GBM disease: no maintenance after 6 months if antibodies cleared.

Monitoring. Daily chest radiograph or gas exchange, haemoglobin, creatinine; weekly antibodies; infection surveillance.

Referral and escalation. Same day nephrology, respiratory medicine, rheumatology and intensive care; haematology or apheresis service for plasma exchange.

Special groups

• Children: methylprednisolone 10 to 30 mg/kg (maximum 1 g) for 3 days; cyclophosphamide 500 mg/m² every 2 to 3 weeks or rituximab 375 mg/m².
• Pregnancy: azathioprine, steroids and plasma exchange; avoid cyclophosphamide and mycophenolate.
• Smokers: higher risk of haemorrhage in anti-GBM disease; advise cessation.