Pulmonary-renal syndrome is not a specific entity but is a syndrome that has a specific 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 of Pulmonary-Renal Syndrome
Pulmonary-renal syndrome is almost always a manifestation of an underlying autoimmune disorder. Goodpasture syndrome Goodpasture Syndrome Goodpasture syndrome, a subtype of pulmonary-renal syndrome, is an autoimmune syndrome consisting of alveolar hemorrhage and glomerulonephritis caused by circulating anti-glomerular basement... read more is the prototype cause, but pulmonary-renal syndrome can also be caused by systemic lupus erythematosus Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more , granulomatosis with polyangiitis Granulomatosis with Polyangiitis (GPA) Granulomatosis with polyangiitis is characterized by necrotizing granulomatous inflammation, small- and medium-sized vessel vasculitis, and focal necrotizing glomerulonephritis, often with crescent... read more , microscopic polyangiitis Microscopic Polyangiitis (MPA) Microscopic polyangiitis is a systemic necrotizing vasculitis without immune globulin deposition (pauci-immune) that affects mainly small vessels. It may begin as a pulmonary-renal syndrome... read more , and, less commonly, by other vasculitides, connective tissue disorders, and drug-induced vasculitides (eg, propylthiouracil—see table Causes of Pulmonary-Renal Syndrome Causes of Pulmonary-Renal Syndrome Pulmonary-renal syndrome is diffuse alveolar hemorrhage plus glomerulonephritis, often occurring simultaneously. Cause is almost always an autoimmune disorder. Diagnosis is by serologic tests... read more ).
Pulmonary-renal syndrome is less commonly a manifestation of immunoglobulin A (IgA)-mediated disorders, such as IgA nephropathy Immunoglobulin A Nephropathy Immunoglobulin A (IgA) nephropathy is deposition of IgA immune complexes in glomeruli, manifesting as slowly progressive hematuria, proteinuria, and, often, renal insufficiency. Diagnosis is... read more or IgA–associated vasculitis Immunoglobulin A–Associated Vasculitis (IgAV) Immunoglobulin A–associated vasculitis (formerly called Henoch-Schönlein purpura) is vasculitis that affects primarily small vessels. It occurs most often in children. Common manifestations... read more , and of immune complex–mediated renal disease, such as essential mixed cryoglobulinemia Cryoglobulinemia Conditions that cause an abnormal protein content in the blood, typically in the form of immunoglobulins, can affect vascular fragility and lead to purpura. (See also Overview of Vascular Bleeding... read more . Rarely, rapidly progressive glomerulonephritis Rapidly Progressive Glomerulonephritis (RPGN) Rapidly progressive glomerulonephritis is acute nephritic syndrome accompanied by microscopic glomerular crescent formation with progression to renal failure within weeks to months. Diagnosis... read more alone can cause the syndrome through a mechanism involving renal failure, volume overload, and pulmonary edema with hemoptysis.
Symptoms and Signs of Pulmonary-Renal Syndrome
Symptoms and signs typically include
Patients may also have other signs of glomerulonephritis Overview of Glomerular Disorders The hallmark of glomerular disorders is proteinuria, which is often in the nephrotic range (≥ 3 g/day). Glomerular disorders are classified based on urine changes as those that manifest predominantly... read more . Pulmonary and renal manifestations can occur weeks to months apart.
Pearls & Pitfalls
Diagnosis of Pulmonary-Renal Syndrome
Sometimes lung and kidney biopsies
Pulmonary-renal syndrome is suspected in patients with hemoptysis not obviously attributable to other causes (eg, pneumonia Overview of Pneumonia Pneumonia is acute inflammation of the lungs caused by infection. Initial diagnosis is usually based on chest x-ray and clinical findings. Causes, symptoms, treatment, preventive measures, and... read more , carcinoma Lung Carcinoma Lung carcinoma is the leading cause of cancer-related death worldwide. About 85% of cases are related to cigarette smoking. Symptoms can include cough, chest discomfort or pain, weight loss... read more , bronchiectasis Bronchiectasis Bronchiectasis is dilation and destruction of larger bronchi caused by chronic infection and inflammation. Common causes are cystic fibrosis, immune defects, and recurrent infections, though... read more ), 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:
Antibodies to double-stranded DNA and reduced serum complement levels: Systemic lupus erythematosus Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more
Antineutrophil cytoplasmic antibodies (ANCA) to proteinase-3 (PR3-ANCA or cytoplasmic ANCA [c-ANCA]): Granulomatosis with polyangiitis Granulomatosis with Polyangiitis (GPA) Granulomatosis with polyangiitis is characterized by necrotizing granulomatous inflammation, small- and medium-sized vessel vasculitis, and focal necrotizing glomerulonephritis, often with crescent... read more
ACNA to myeloperoxidase (MPO-ANCA, or perinuclear ANCA [p-ANCA]): Microscopic polyangiitis Microscopic Polyangiitis (MPA) Microscopic polyangiitis is a systemic necrotizing vasculitis without immune globulin deposition (pauci-immune) that affects mainly small vessels. It may begin as a pulmonary-renal syndrome... read more
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 Overview of Tests of Pulmonary Function Pulmonary function tests provide measures of airflow, lung volumes, gas exchange, response to bronchodilators, and respiratory muscle function. Basic pulmonary function tests available in the... read more and bronchoalveolar lavage are not diagnostic 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 when hematocrit is falling.
Treatment of Pulmonary-Renal Syndrome
Immunosuppression is the cornerstone of treatment of pulmonary-renal syndrome. Standard induction-remission regimens include pulse IV methylprednisolone (500 to 1000 mg IV once a day for 3 to 5 days). As life-threatening features subside, the corticosteroid dose can be reduced; 1 mg/kg prednisone (or equivalent) orally once a day is given for the first month, then tapered over the next 3 to 4 months.
Cyclophosphamide 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 a month or orally (1 to 2 mg/kg once a day). Rituximab may be used instead of cyclophosphamide; it is non-inferior and causes fewer adverse effects.
Plasma exchange Plasma exchange Apheresis refers to the process of separating the cellular and soluble components of blood using a machine. Apheresis is often done on donors where whole blood is centrifuged to obtain individual... read more is also often used, particularly in Goodpasture syndrome Treatment Goodpasture syndrome, a subtype of pulmonary-renal syndrome, is an autoimmune syndrome consisting of alveolar hemorrhage and glomerulonephritis caused by circulating anti-glomerular basement... read more and certain vasculitides.
Transition to maintenance therapy may occur 6 to 12 months 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.
The most suggestive clue to pulmonary-renal syndrome 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 kidney biopsy.
Treat underlying autoimmune disorders.