Pulmonary-Renal Syndrome

Pulmonary-renal syndrome is almost always a manifestation of an underlying autoimmune disorder. Anti-glomerular basement membrane (anti-GBM) disease is considered the prototype cause, but pulmonary-renal syndrome can also be caused by granulomatosis with polyangiitis, microscopic polyangiitis, and, less commonly, by systemic lupus erythematosus, cryoglobulinemia, drug-induced vasculitides, IgA nephropathy, or IgA–associated vasculitis. Rarely, rapidly progressive glomerulonephritis alone can cause the syndrome through a mechanism involving kidney failure, volume overload, and pulmonary edema with hemoptysis (see table Causes of Pulmonary-Renal Syndrome).

Symptoms and signs typically include:

• Cough

• Dyspnea

• Fever

• Hematuria

• Hemoptysis

• Peripheral edema

Patients may also have other signs of glomerulonephritis. Pulmonary and renal manifestations can occur weeks to months apart.

Occasionally, the disease presents as sudden, acute exacerbations of the above symptoms and signs.

• Laboratory testing, including urinalysis

• Imaging (chest radiographs and CT)

• Sometimes pulmonary function tests and bronchoscopy with lavage

• Serologic tests to determine the underlying cause

• Sometimes lung and kidney biopsies

Pulmonary-renal syndrome is clinically suspected in patients with hemoptysis not obviously attributable to other causes (eg, pneumonia, carcinoma, bronchiectasis), particularly when hemoptysis is accompanied by diffuse parenchymal infiltrates and findings suggesting renal disease.

Initial testing includes urinalysis for evidence of hematuria and red cell casts (suggesting glomerulonephritis), serum creatinine for renal function assessment, and a complete blood count (CBC) for evidence of anemia. Chest radiography and CT scans may reveal the presence of bilateral diffuse infiltrates (on radiographs) or ground glass opacifications (on CT).

Serum autoantibody testing may help distinguish some causes, as in the following (1):

• Antiglomerular basement membrane antibodies: Anti-glomerular basement membrane (anti-GBM) disease

• Antibodies to double-stranded DNA and reduced serum complement levels: Systemic lupus erythematosus

• Antineutrophil cytoplasmic antibodies (ANCA) to proteinase-3 (PR3-ANCA or cytoplasmic ANCA [c-ANCA]): Granulomatosis with polyangiitis

• ACNA to myeloperoxidase (MPO-ANCA, or perinuclear ANCA [p-ANCA]): Microscopic polyangiitis

Bronchoalveolar lavage can be used to support the diagnosis of alveolar hemorrhage, in those with and without hemoptysis. Lavage fluid that becomes increasingly hemorrhagic after sequential sampling, and the presence of hemosiderin-laden macrophages is a hallmark cytologic feature of blood in the alveolar space. Pulmonary function tests are not diagnostic but can be a helpful adjunct.

Definitive diagnosis requires renal or lung biopsy to confirm the underlying histopathologic process and can help distinguish between etiologies (eg, anti-GBM disease, ANCA-associated vasculitis).

• Typically immunosuppressive therapy (eg, glucocorticoids, cyclophosphamide, rituximab, avacopan)Typically immunosuppressive therapy (eg, glucocorticoids, cyclophosphamide, rituximab, avacopan)

• Sometimes plasma exchange

Immunosuppression is the cornerstone of treatment of pulmonary-renal syndrome (1). Standard induction-remission regimens include pulse IV methylprednisolone once a day for 3 to 5 days. As life-threatening features subside, the glucocorticoid dose can be reduced; for example, prednisone 1 mg/kg (or equivalent) orally once a day is given for the first month, then tapered over the next 3 to 4 months.). Standard induction-remission regimens include pulse IV methylprednisolone once a day for 3 to 5 days. As life-threatening features subside, the glucocorticoid dose can be reduced; for example, prednisone 1 mg/kg (or equivalent) orally once a day is given for the first month, then tapered over the next 3 to 4 months.

The choice of an additional immunosuppressive therapy is guided by the underlying disease. For example, in patients with pulmonary-renal syndrome due to ANCA-associated vasculitis, treatment with rituximab or cyclophosphamide is typically initiated. Avacopan, a complement C5a receptor antagonist, may also be considered as a glucocorticoid-sparing agent., treatment with rituximab or cyclophosphamide is typically initiated. Avacopan, a complement C5a receptor antagonist, may also be considered as a glucocorticoid-sparing agent.

Plasma exchange is also often used, particularly in anti-glomerular basement membrane disease and certain refractory vasculitides.

The approach to and duration of maintenance therapy also depends on the specific disease being treated.