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Pulmonary-Renal Syndrome

by Marvin I. Schwarz, MD

Pulmonary-renal syndrome (PRS) is diffuse alveolar hemorrhage plus glomerulonephritis, often 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 segmental proliferative glomerulonephritis.

Etiology

PRS is almost always a manifestation of an underlying autoimmune disorder. Goodpasture syndrome is the prototype cause, but PRS can also be caused by SLE, granulomatosis with polyangiitis (formerly known as Wegener granulomatosis), microscopic polyangiitis, and, less commonly, by other vasculitides, connective tissue disorders, and drug-induced vasculitides (eg, propylthiouracil —see Table: Causes of Pulmonary-Renal Syndrome).

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.

Causes of Pulmonary-Renal Syndrome

Disorder

Examples

Connective tissue disorders

Polymyositis or dermatomyositis

Progressive systemic sclerosis

RA

SLE

Goodpasture syndrome

Renal disorders

Idiopathic immune complex glomerulonephritis

IgA nephropathy

Rapidly progressive glomerulonephritis with heart failure

Systemic vasculitis

Behçet syndrome

Churg-Strauss syndrome

Cryoglobulinemia

Henoch-Schönlein purpura

Microscopic polyarteritis

Granulomatosis with polyangiitis

Other

Drugs (eg, propylthiouracil)

Heart failure

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. Pulmonary and renal manifestations can occur weeks to months apart.

Pearls & Pitfalls

  • Consider pulmonary renal syndrome in patients with findings compatible with alveolar hemorrhage and glomerulonephritis even when pulmonary and renal findings occur at different times.

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 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]): granulomatosis with polyangiitis

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

Definitive diagnosis requires lung biopsy with findings of small-vessel vasculitis or 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 cyclophosphamide

  • Plasma exchange

Immunosuppression is the cornerstone of treatment. Standard induction-remission regimens include pulse IV methylprednisolone (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 prednisone (or equivalent) po once/day is given for the first month, then tapered over the next 3 to 4 mo. Cyclophosphamide should be added to corticosteroid therapy in critically ill patients with generalized disease, at a dose of 0.5 to 1 g/m 2 IV given as a pulse once/mo or orally (1 to 2 mg/kg once/day). Plasma exchange is also often used, particularly in Goodpasture syndrome and certain vasculitides.

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.

Key Points

  • The most suggestive clue to PRS is often that patients have both unexplained pulmonary and renal symptoms, even when such symptoms occur at different times.

  • Do routine laboratory tests (including urinalysis and chest x-ray) as well as autoantibody testing.

  • Confirm the diagnosis when necessary with lung or renal biopsy.

  • Treat underlying autoimmune disorders.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • No US brand name
  • CYTOXAN (LYOPHILIZED)
  • MEDROL
  • RAYOS

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