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Pulmonary-renal syndrome (PRS) is diffuse alveolar hemorrhage and glomerulonephritis occurring simultaneously. Cause is almost always an autoimmune disorder. Diagnosis is by serologic tests and sometimes lung and renal biopsy. Treatment typically includes immunosuppression with corticosteroids and cytotoxic drugs.

PRS is not a specific entity but is a syndrome that suggests a differential diagnosis and a specific sequence of testing.

Pulmonary pathology is small-vessel vasculitis involving arterioles, venules, and, frequently, alveolar capillaries. Renal pathology is small-vessel vasculitis resulting in a form of focal proliferative glomerulonephritis.

Etiology

PRS is almost always a manifestation of an underlying autoimmune disorder. Goodpasture's syndrome is the prototype cause, but PRS can also be caused by SLE, Wegener's granulomatosis, microscopic polyangiitis, and, less commonly, by other vasculitides and connective tissue disorders (see Table 1: Diffuse Alveolar Hemorrhage and Pulmonary-Renal Syndrome: Causes of Pulmonary-Renal Syndrome).

Table 1
Causes of Pulmonary-Renal Syndrome Disorder Examples Connective tissue disorders Polymyositis or dermatomyositis Progressive systemic sclerosis RA SLE Goodpasture's syndrome — Renal disorders Idiopathic immune complex glomerulonephritis IgA nephropathy Rapidly progressive glomerulonephritis with heart failure Systemic vasculitis Behçet's syndrome Churg-Strauss syndrome Cryoglobulinemia Henoch-Schönlein purpura Microscopic polyarteritis Wegener's granulomatosis Other Drugs (eg, penicillamineSome Trade Names CUPRIMINE Click for Drug Monograph ) Heart failure

PRS is less commonly a manifestation of IgA-mediated disorders, such as IgA nephropathy or Henoch-Schönlein purpura, and of immune complex–mediated renal disease, such as essential mixed cryoglobulinemia. Rarely, rapidly progressive glomerulonephritis alone can cause PRS through a mechanism involving renal failure, volume overload, and pulmonary edema with hemoptysis.

Symptoms and Signs

Symptoms and signs typically include dyspnea, cough, fever, and hemoptysis in combination with peripheral edema and hematuria or other signs of glomerulonephritis.

Diagnosis

• Serologic testing
• Sometimes lung and renal biopsies

PRS is 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 CBC for evidence of anemia. Chest x-ray is done if not yet obtained.

Serum antibody testing may help distinguish some causes, as in the following:

• Antiglomerular basement membrane antibodies: Goodpasture's syndrome
• Antibodies to double-stranded DNA and reduced serum complement levels: SLE
• Antineutrophil cytoplasmic antibodies (ANCA) to proteinase-3 (PR3-ANCA or cytoplasmic ANCA [c-ANCA]): Wegener's granulomatosis
• ACNA to myeloperoxidase (MPO-ANCA, or perinuclear ANCA [p-ANCA]): Microscopic polyangiitis

Definitive diagnosis requires lung biopsy with findings of small-vessel vasculitis and renal biopsy with findings of glomerulonephritis with or without antibody deposition.

Pulmonary function tests and bronchoalveolar lavage are not diagnostic of PRS but can be used to help confirm diffuse alveolar hemorrhage in patients with glomerulonephritis and pulmonary infiltrates but without hemoptysis. Lavage fluid that remains hemorrhagic after sequential sampling establishes diffuse alveolar hemorrhage, especially in the context of falling Hct.

Treatment

• Corticosteroids
• Sometimes cyclophosphamideSome Trade Names
  CYTOXAN
  Click for Drug Monograph
  

Immunosuppression is the cornerstone of treatment. Standard induction-remission regimens include pulse IV methylprednisoloneSome Trade Names
MEDROL
Click for Drug Monograph
(500 to 1000 mg IV once/day for 3 to 5 days). As life-threatening features subside, the corticosteroid dose can be reduced; 1 mg/kg prednisoneSome Trade Names
DELTASONE
Click for Drug Monograph
(or equivalent) po once/day is given for the first month, then tapered over the next 3 to 4 mo. CyclophosphamideSome Trade Names
CYTOXAN
Click for Drug Monograph
should be added to corticosteroid therapy in critically ill patients with generalized disease, at a dose of 0.5 to 1 g/m² IV given as a pulse once/mo or orally (1 to 2 mg/kg once/day).

Transition to maintenance therapy may occur 6 to 12 mo after the initiation of induction therapy or after clinical remission. Maintenance therapy includes low-dose corticosteroids coupled with cytotoxic agents. However, relapse may occur despite ongoing therapy.

Last full review/revision July 2009 by Marvin I. Schwarz, MD

Content last modified July 2009