AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Goodpasture syndrome (GS) is the clinical entity of acute glomerulonephritis and pulmonary alveolar hemorrhage. It is rarely seen in children. The term Goodpasture syndrome is used interchangeably with pulmonary renal syndrome. Goodpasture syndrome has a number of underlying etiologies and often occurs in the setting of a small vessel vasculitis associated with antineutrophil cytoplasmic autoantibodies (ANCAs); examples include Wegener granulomatosis and microscopic polyangiitis.

Goodpasture's name has been used in a more specific clinical condition known as Goodpasture disease, which is the pulmonary renal syndrome specifically associated with anti–glomerular basement membrane (anti-GBM) antibodies. These anti-GBM antibodies produce a characteristic linear deposition along the glomerular basement membrane (GBM), one way in which Goodpasture syndrome is differentiated from Wegener granulomatosis. Because pulmonary renal syndrome is discussed extensively in the eMedicine article Wegener Granulomatosis, this article focuses on the specific form of this syndrome associated with anti-GBM antibodies. To avoid confusion between Goodpasture syndrome and Goodpasture disease, the term anti-GBM disease is used.

Anti-GBM disease is defined as the triad of glomerulonephritis (usually rapidly progressive or crescentic), pulmonary hemorrhage, and anti-GBM antibody formation. Despite this triad of clinical findings, patients with anti-GBM disease may present with a spectrum of conditions ranging from pulmonary hemorrhage with minimal or no renal involvement to full-blown renal failure with limited or no pulmonary involvement. Because of limited experience with the disease in children, much of the information presented in this article is derived from the literature about adults.

In 1919, Ernest Goodpasture described an 18-year-old man with a fever and cough, followed by hemoptysis and renal failure. On the basis of this clinical report, Goodpasture's name is often linked to the pulmonary renal syndrome of alveolar hemorrhage and necrotizing and proliferative glomerulonephritis, although vasculitis and not anti-GBM disease is believed to be the cause of the pulmonary renal syndrome in Goodpasture's original patient. The discovery of the role of anti-GBM antibodies by Lerner et al in 1967 helped provide both a better understanding of the pathogenesis for this specific form of pulmonary renal syndrome and a more rational approach to treatment.

Pathophysiology

Pathogenesis of anti-GBM disease is linked to the presence of autoantibodies that react with the alveolus in the lung and the basement membrane of the glomerulus in the kidney. Anti-GBM autoantibodies that are present in the circulation of patients with anti-GBM disease cross the fenestrated endothelium in the glomerulus and bind with the underlying GBM, inducing renal injury.

Anti-GBM antibodies interact with the GBM glycoproteins, almost exclusively the epitope of the noncollagenous domain (NC1) of the a3 chain of type IV collagen. This interaction results in complement activation with glomerular infiltration of polymorphonuclear leukocytes and monocytes. Fibrinogen leaks through the damaged GBM into the Bowman space, and it is polymerized to fibrin through procoagulant factors from activated monocytes, resulting in crescent formation. These autoantibodies are believed to cross-react with the alveolar basement membrane and cause similar damage.

The degree of cross-linking of the a3NC1 hexamer subunits is approximately 3 times greater in the alveolar basement membrane than in the GBM. The Col 4a3NC1 epitope is thought to be less accessible for anti-GBM binding in the lung, and partial denaturation of NC1 domains may be required for full exposure of this sequestered epitope to the antibody. If true, this theory may explain why pulmonary hemorrhage is often associated with factors that increase pulmonary capillary permeability, such as active cigarette smoking, infections, recent hydrocarbon inhalation, and hyperoxia.

Etiology of anti-GBM production is not yet well understood. An animal model for anti-GBM disease has demonstrated that a 10 amino acid, nephritogenic, T-cell epitope of Col4alpha3NC1 was capable of inducing an anti-GBM glomerulonephritis in rats. Goodpasture's positive association with human leukocyte antigen (HLA) DRB1*1501 is among the strongest reported for autoimmune diseases. A positive association with HLA-DR4 also exists. Anti-GBM disease is seen less often with HLA-DR1 and HLA-DR7. Genetic predisposition may be a factor, along with a second environmental insult, such as exposure to cigarette smoke, inhaled hydrocarbons, or viruses.

Frequency

United States

Anti-GBM is rare in adults and children. According to the 1999 United States Renal Data System (USRDS) Annual Data Report, from 1993-1997, Goodpasture syndrome was the underlying cause of end-stage renal disease (ESRD) in 37 pediatric patients younger than 20 years. Presumably, the term Goodpasture syndrome referred to anti-GBM disease, because other causes for the pulmonary renal syndrome that contributed to ESRD (eg, systemic lupus erythematosus [SLE], Henoch-Schönlein purpura [HSP], Wegener granulomatosis) were all listed separately.

International

The annual incidence is estimated to be 1 case per 2 million population among white Europeans. A recent retrospective study of ESRD in Dutch children from 1987-2001 listed Goodpasture syndrome as the primary cause of renal failure in 4 (1.1%) of 351 cases.

Mortality/Morbidity

• Pulmonary hemorrhage: If fulminant pulmonary hemorrhage occurs, it can lead to respiratory failure, which may result in death.
• Renal failure: Renal disease may be indolent, resulting in advanced and often irreversible disease at the time of presentation. Renal failure usually requires dialysis, and patients requiring dialysis at presentation usually develop ESRD.

Race

Anti-GBM disease has been described in many racial groups, but whites are affected most often. According to the 1999 USRDS Annual Data Report, 33 (89%) of 37 pediatric patients seen over a 5-year period were white.

Sex

• Pediatric literature indicates no predilection in either sex. According to the 1999 USRDS Annual Data Report (1993-1997 data), 49% of young patients (<20 y) who developed ESRD (termed GS by the USRDS) were male.
• In adults, reports indicate a male-to-female ratio of 2:1 to 9:1. The literature about adults has also shown that anti-GBM disease with pulmonary renal syndrome typically occurs in young men, whereas renal disease that occurs in isolation is more common in elderly women.

Age

• In children, anti-GBM disease has been reported in all ages. An 11-month-old infant is the youngest reported patient. The 1999 USRDS Annual Data Report indicated that, in 1993-1997, what the USRDS termed Goodpasture syndrome was the underlying cause of ESRD in 37 pediatric patients younger than 20 years. The median age of these patients was 16 years.
• In the few pediatric cases of anti-GBM disease reported, some children presented with limited renal disease, and others presented with pulmonary hemorrhage alone. In one child, a diagnosis of pulmonary hemosiderosis was made 4 years before anti-GBM disease was seen. Anti-GBM–mediated renal disease resulted in ESRD in most children.
• In adults, the mean age of onset is 20-30 years, with a peak incidence in young men aged 20-30 years. A second peak occurs in those aged 50-70 years, with men and women equally affected.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Hemoptysis is the most common presenting symptom, followed by dyspnea, fatigue or weakness or both, and cough.

• Renal disease may be present in anti-GBM disease. When present, it can be isolated or accompanied by pulmonary hemorrhage. Signs include the following:
• • Gross hematuria (10-41% of adults)
  • Edema (in as many as 25% of patients)
• Pulmonary hemorrhage can range from mild to life threatening. Symptoms include the following:
• • Hemoptysis (82-90% of adults)
  • Cough (40-60% of adults)
  • Exertional dyspnea (57-72% of adults)
  • Fatigue and weakness (38-66% of adults)
  • Fevers, chills, diaphoresis (15-24% of adults)
  • Tachypnea
  • Cyanosis
  • Inspiratory crackles
  • Bronchial breathing
• The general features listed below are more prominent in patients with systemic vasculitis than in others. The following can be the initial signs or symptoms in patients with anti-GBM disease:
• • Malaise
  • Weight loss
  • Arthralgias
  • Fever
  • Pallor (correlated with degree of anemia present; approximately 51-90% of adults have pallor)

Physical

Physical examination findings in patients with anti-GBM disease are those related to pulmonary hemorrhage, renal failure, and anemia and include pallor (the most common clinical sign), crackles and rhonchi, heart murmur, hepatomegaly, and edema.

• Pulmonary symptoms
• • Hemoptysis can vary from blood-tinged sputum to profound bleeding.
  • Mild hemoptysis may resolve spontaneously or progress to massive hemorrhage in a short period, resulting in fulminant respiratory failure.
  • In approximately two thirds of cases, hemoptysis precedes the onset of renal disease by 8-12 months. This interval can be as long as 12 years before nephritis develops.
  • Exertional dyspnea likely reflects both lung parenchymal involvement and anemia from pulmonary hemorrhage.
  • In severe cases, clinical signs of pulmonary hemorrhage include tachypnea, inspiratory crackles and rhonchi, and cyanosis.
  • Prompt diagnosis of pulmonary hemorrhage is imperative, because it is the principal cause of early death in patients with anti-GBM disease.
  • Pulmonary hemorrhage is probably less common in adults than previously reported because of the decreasing prevalence of cigarette smoking.
• Renal symptoms
• • Signs and symptoms of disease can vary from hematuria and proteinuria with normal renal function to severe oligoanuric renal failure.
  • Hypertension can be present, but it is an uncommon form of glomerulonephritis, reported in 4-17% of adult patients.
  • Similarly, hypertension is unusual in children, but it has been reported.
  • When significant renal disease is present, it usually progresses rapidly.
  • Adults presenting with a serum creatinine level greater than 6 mg/dL have a worse prognosis.
• Anemia: Approximately 20-25% of patients have a functional heart murmur because of anemia.
• Generalized vasculitis
• • Unlike patients with ANCA disease, patients with anti-GBM disease typically lack symptoms of generalized vasculitis.
  • Approximately 20-30% of adults with anti-GBM disease have coexisting ANCA in their circulation. The renal prognosis of these patients is better when both antibodies are present than when anti-GBM is present alone.

Causes

Anti-GBM antibodies cause this autoimmune disorder, usually when a genetically predisposed individual encounters a particular environmental insult.

• Genetic predispositions
• • Anti-GBM antibody has been described in identical twins, siblings, and first cousins.
  • HLA-DR2 is expressed in 88% of patients with anti-GBM disease compared to 25-32% of a control group of blood donors.
  • Simultaneous expression of HLA-B8 and HLA-DR2 is associated with a worse prognosis because of the tendency to form glomerular crescents.
  • Anti-GBM antibody is strongly associated with HLA-DR15 and HLA-DR4 alleles.
  • HLA-DR7 and HLA-DR1 have strong negative associations; both are highly protective.
• Environmental insults
• • Cigarette smoking: Smoking is closely linked with hemoptysis. In one large series, 47 of 51 adult patients with anti-GBM disease had a history of smoking. In all, 37 of 37 smokers experienced pulmonary hemorrhage compared with 2 of 10 nonsmokers. Pulmonary hemorrhage is probably less common in adults than previously reported because of the decreasing prevalence of cigarette smoking.
  • Inhaled hydrocarbons: Exposure to hydrocarbon solvents has been associated with anti-GBM disease. Gasoline fumes or industrial solvents are believed to induce chemical injury to the lung or kidney, stimulating antibody production. In one pediatric report, anti-GBM disease developed in a 16-year-old adolescent girl who engaged in heavy smoking and glue sniffing.
  • Viral infections: Influenza type A2 has been associated with anti-GBM disease. Upper respiratory tract infection or flulike illness occurred before the onset of disease in 20-61% of adults with anti-GBM disease.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Essential mixed cryoglobulinemia

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• All patients require urinalysis; CBC count with differential; and assessments of BUN, creatinine, and electrolyte levels.
• The erythrocyte sedimentation rate is usually only mildly elevated, unlike in patients with vasculitis.
• Specific serologic tests include assessments of anti-GBM titers and ANCA titers through indirect immunofluorescence testing, as well as enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA), to evaluate proteinase 3 and myeloperoxidase.
• • Results from serologic studies such as antistreptolysin O (ASO) titers and complement studies are usually normal.
  • Circulating anti-GBM titers may be elevated in more than 90% of patients.
  • ANCA titers are elevated in 20-30% of patients with anti-GBM disease. The ANCA titer is usually perinuclear antineutrophil cytoplasmic autoantibody (p-ANCA) from antimyeloperoxidase antibody.
• Assessments of antinuclear antibody (ANA), C3, and C4 levels and of the Westergren sedimentation rate are recommended. Test results for ANA and rheumatoid factor are usually negative.
• Tests for anti-GBM antibodies may be helpful.
• • The presence of anti-GBM antibody formation can be determined in a number of ways.
  • Linear immunoglobulin G (IgG) deposition along the glomerular capillary walls on the immunofluorescence portion of the renal biopsy is highly suggestive of the disease, especially in the setting of crescentic glomerulonephritis.
  • Circulating anti-GBM antibodies, which are typically of the IgG class, can be documented through indirect immunofluorescence or RIA techniques. Compared with indirect immunofluorescence, RIA is more sensitive (>90%) and almost as specific (>98%).
  • IgG can occasionally be eluted from lung or kidney biopsy tissue for analysis and characterization.
• Anemia occurs out of proportion to hemoptysis or renal failure.
• • A hemoglobin level less than 12 mg/dL is observed in 90-100% of adults.
  • In one series involving adults, the mean hemoglobin level was 7.5 g/dL.
• Leukocytosis may be present. Approximately 40-50% of adults have a white blood cell (WBC) count of greater than 10,000/mm³. A leftward shift is common.
• Azotemia occurs in 55-71% of adults with anti-GBM disease.
• Hematuria may be present.
  • Microscopic hematuria, as defined by the presence of red blood cells (RBCs), occurs in 83-94% of adults with anti-GBM disease.
  • Macroscopic hematuria is present in 10-40% of adults. RBC casts have been reported in 6-100% of adults with anti-GBM disease.
• Proteinuria occurs in 76-100% of adults. Nephrotic syndrome is unusual.

Imaging Studies

• Chest radiography is the most useful imaging test available to document the presence of pulmonary hemorrhage.
• • Chest radiographic findings depict patchy or diffuse infiltrates with sparing of the upper lung fields.
  • Unlike infection, pulmonary infiltrates from hemorrhage may resolve within a few days.
• Chest CT has a more limited role, but it may be helpful in identifying localized areas of hemoptysis.

Other Tests

• Pulmonary function testing can be used to assess pulmonary hemorrhage by demonstrating accelerated diffusing capacity of lung for carbon monoxide (DLCO). A progressive decline in vital capacity or total lung capacity suggests developing interstitial fibrosis
• Pulse oximetry is indicated in all patients with suspected anti-GBM disease who may have hypoxemia from their parenchymal lung injury. However, in patients with severe anemia, oximeter readings may become less accurate.

Procedures

• Renal biopsy can usually be performed without incident, even in a patient in relatively unstable condition.
• • Biopsy allows assessment of the severity of the glomerulonephritis and examination for the characteristic linear IgG deposition along the GBM.
  • Compared with lung biopsy, renal biopsy is a superior diagnostic test.
• Lung biopsy is rarely indicated, but it may be helpful.
• • In comparison, bronchoscopy with transbronchial forceps biopsy (TBB) has a higher rate of false-negative results, but it is less invasive than collection through open lung biopsy. TBB is technically more difficult in younger children, and the small biopsy forceps used in them results in smaller tissue samples, with lower diagnostic yield.
  • Bronchoalveolar lavage can be used to detect hemosiderin-laden macrophages.

Histologic Findings

Renal biopsy: Renal biopsy shows a diffuse glomerulonephritis with focal or complete necrosis of the glomerular tuft and segmental or circumferential cellular crescents surrounding some or all glomeruli. Linear IgG along the GBM can be observed with immunofluorescence testing. Linear C3 along the GBM is present in two thirds of biopsy samples. Other causes of linear staining on direct immunofluorescence analysis include SLE and diabetes mellitus.

Lung biopsy usually shows nonspecific findings of hemorrhage with variable degrees of inflammation and fibrosis. Samples obtained during lung biopsy may show IgG staining of the alveolar septum, which is diagnostic for anti-GBM disease.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Treatment of anti-GBM disease requires a 2-pronged approach consisting of the removal of the pathogenic antibody and the prevention of new antibody production.

• Plasma exchange: For antibody removal, literature about adults recommends plasma exchange every day for 14 days or every third day for a month. Each session consists of an exchange volume of 3-4 L and its replacement with albumin or fresh-frozen plasma.
• Immunosuppression: Therapy with corticosteroids (eg, prednisone) and cyclophosphamide is aimed at eliminating ongoing antibody synthesis. Adult patients who present with a serum creatinine level greater than 8 mg/dL have poor renal outcomes. Therefore, seriously consider whether to use this aggressive treatment regimen in patients presenting with limited pulmonary disease and marked renal impairment (serum creatinine >8 mg dL).
• • Isolated reports describe the use of rituximab, an anti-CD20 monoclonal antibody, in autoimmune disorders aimed at targeting B lymphocytes and their antibody production.
  • Arzoo reported its use in a 73-year-old woman whose recurrent anti-GBM disease was refractory to treatment with steroids, plasmapheresis, and cyclophosphamide. This patient had marked improvement after the second of 6 weekly prescribed doses of rituximab at 375 mg/m²/dose. This coincided with the disappearance of circulating anti-GBM antibodies.
• Pediatric anti-GBM disease: Pediatric patients have also been given plasma exchange in conjunction with corticosteroids and cyclophosphamide. Duration of the immunosuppressive treatment varies, but it is typically 6 months for steroids and 3 months for cyclophosphamide. Rituximab has been used in pediatric autoimmune disorders, but no reports exist of its use for anti-GBM disease in the pediatric age group. This agent is a potent immunosuppressive and needs to be used with caution, weighing the risks and benefits (see Medication).
• Monitoring the therapeutic response: Closely monitor patients by obtaining regular anti-GBM titers, serum creatinine levels, and chest radiographs to decide on the duration of various therapies.

Consultations

• Patients with anti-GBM disease can present with renal or pulmonary symptoms and are often critically ill. Therefore, pulmonologists, nephrologists, and critical care specialists are commonly involved in the care of these patients.
• Most treatments are aimed at both renal and pulmonary conditions. Effective cooperation and communication with regard to the timing and duration of these therapies is essential.

Diet

• Sodium restriction
• • Pediatric patients taking corticosteroids are restricted to a sodium intake of 3 mEq/kg/d. The daily total should not exceed 2 g. On the basis of the molecular weight of sodium, 1 mEq is equal to 23 mg.
  • Pediatric patients with severe proteinuria and nephrotic syndrome who are taking corticosteroids are restricted to a sodium intake of 2 mEq/kg/d. The daily total should not exceed 2 g.
• Fluid restriction
• • The recommended fluid intake largely depends on the patient's renal function and whether the patient is taking cyclophosphamide.
  • Patients with a good urine output and a stable blood pressure do not require fluid restriction. Moreover, if the same patients are taking cyclophosphamide, liberal fluid intake is encouraged to promote urine output and to prevent the risk of hemorrhagic cystitis.
  • Conversely, patients with oliguric renal failure who are not likely to be taking cyclophosphamide may require fluid restriction.

Activity

Once discharged from the hospital, recovering patients can resume their usual activities unless they have undergone renal biopsy. These patients should avoid running and jumping for 2 weeks, and they are restricted from contact sports for 1 month after the date of biopsy.

If significant anemia is present, the patient's tendency to become fatigued is likely to restrict his or her usual activity level.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medications used to treat anti-GBM disease are immunosuppressive agents and prophylactic antibiotics.

Drug Category: Glucocorticoids

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.

Drug Category: Alkylating agent (cytotoxic agent)

Cyclophosphamide interferes with inflammatory response by decreasing bone marrow response through the interference of DNA cross-linking. Decreases anti-GBM antibody production.

Drug Category: Monoclonal antibodies

Rituximab (anti-CD-20) monoclonal antibody binds to pre-B cells and mature B cells. It results in lymphocytotoxic effects to B cells, which should result in reduced autoantibody production.

Drug Category: Antibiotics

These agents are used to prevent opportunistic infection with Pneumocystis carinii.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Continued treatment is necessary for the following potential complications of anti-GBM disease:
• • Relapse of anti-GBM disease (ie, pulmonary hemorrhage, deterioration of renal function)
  • Need to initiate dialysis
  • Complications related to dialysis
  • Need for kidney transplant
  • Opportunistic infections

Further Outpatient Care

• Perform CBC count weekly to monitor for leukopenia or thrombocytopenia while the patient is taking cyclophosphamide.
• Outpatient clinic visits may be required to monitor the patient's blood pressure, renal function, and pulmonary function. Pulmonary function and hemorrhage can be monitored with pulmonary function testing and DLCO measurements.
• Patients may receive peritoneal dialysis or hemodialysis. Peritoneal dialysis can be performed daily at home, whereas hemodialysis is typically performed 3 times per week at a dialysis center.
• Adults needing plasma exchange receive 4-L exchanges every 3 days for 1 month. An alternate approach is daily exchange for 2 weeks or until the circulating anti-GBM titer is negative. The replacement fluid is usually human albumin, but fresh-frozen plasma may be used in select circumstances.
• Pediatric patients may receive exchange volumes of 0.5-3.8 L, depending on their size. The treatments are typically given daily for approximately 10 days or until the anti-GBM titer has decreased to normal levels.

In/Out Patient Meds

• Medications include prednisone, cyclophosphamide, and trimethoprim-sulfamethoxazole.
• Antihypertensives may be required if hypertension occurs.
• Calcium channel blockers (eg, extended-release nifedipine) and diuretics are useful.
• Angiotensin-converting enzymes should be used with caution because they may increase serum potassium levels and decrease renal function.
• Avoid beta-blockers as well in light of the patient's pulmonary disease.
• Clindamycin lotion can be used topically to treat steroid-induced acne.

Transfer

• A severely ill patient with anti-GBM disease may need to be transferred if the hospital has insufficient intensive care support.
• Extracorporeal membrane oxygenation (ECMO) has been tried in pediatric patients with severe pulmonary involvement that is unresponsive to conventional ventilatory support. Transfer to a tertiary care center may be needed if such circumstances are impending.

Deterrence/Prevention

• Because the disease can recur, minimize environmental risk factors associated with this disease (eg, cigarette smoking, hydrocarbon exposure).

Complications

• Complications of plasma exchange include the following:
• • Anaphylactoid reactions, usually when fresh-frozen plasma is used
  • Metabolic alkalosis from solutions with high citrate and low chloride, especially when renal function is poor
  • Hemorrhage or thrombosis
  • Posttransfusion hepatitis
• Although theoretically possible, relapse of anti-GBM disease is relatively uncommon. Recurrent pulmonary hemorrhage associated with infection or cigarette smoking has been reported in adults.
• Opportunistic infections can occur secondary to the patient's immunosuppressed state. Fungal, opportunistic bacterial, and catheter-related infections should be considered in these patients, especially if they are receiving triple therapy with corticosteroids, cyclophosphamide, and plasma exchange.
• ESRD may result.

Prognosis

• Prognosis has greatly improved in the past 15 years, because plasma exchange has been used more aggressively. Reports from the 1960s, before the advent of immunosuppressive therapy and plasma exchange, indicate a 96% mortality rate in adults; in the era of plasma exchange, the mortality rate in adults is 0-41%.
• Pulmonary prognosis is usually excellent. Some adult patients have had a low DLCO, which suggests residual pulmonary fibrosis.
• Renal prognosis
• • Fewer than 20 cases of immunologically confirmed anti-GBM renal disease have been reported in children. Approximately 90% of patients developed ESRD, and 3 died.
  • The literature on adults suggests that patients presenting with oligoanuria and serum creatinine level of 6-7 mg/dL do not recover their renal function. Before the advent of plasma exchange, renal survival (with no need for dialysis or transplantation) was less than 25% in adults. According to the current literature about adults, the incidence of ESRD in anti-GBM disease is 25-69%. More recent reports indicate a better outcome with the aggressive use of plasma exchange.
  • A single-center, retrospective study of 71 patients over 25 years reported excellent patient and renal survival for patients presenting with a serum creatinine level of less than 5.7 mg/dL. Those who had a creatinine level greater than 5.7 mg/dL and were not dialysis-dependent at presentation had an 82% renal survival at 1 year and 69% at their last follow-up visit.
  • Those who were dialysis-dependent at presentation had a 1-year renal survival of 8%, which fell to 5% at the last follow-up visit. The authors concluded that aggressive use of immunosuppression and plasma exchange should be expeditiously instituted in patients with anti-GBM disease with severe renal involvement to attempt to optimize the chance of renal recovery.
• Transplantation: A recent comprehensive review by Knoll et al stated that patients with anti-GBM disease and ESRD should be candidates for a renal transplant if they have undetectable anti-GBM titers and are in clinical remission off alkylating agents for at least 6 months.

Patient Education

• Because relapse can occur, patients should be educated regarding the potential signs and symptoms of such a relapse.
• Pulmonary relapse can result in a cough, dyspnea, or fatigue.
• If these symptoms arise, medical attention should be sought immediately because of the potential life-threatening nature of pulmonary hemorrhage.
• For excellent patient education resources, visit eMedicine's Kidneys and Urinary System Center and Procedures Center. Also, see eMedicine's patient education articles Blood in the Urine and Bronchoscopy.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to educate patients
• Failure to monitor for leukopenia or thrombocytopenia
• Failure to monitor blood pressure, renal function, and pulmonary function
• Anaphylactoid reactions, which usually occur when fresh-frozen plasma is used
• Posttransfusion hepatitis
• Failure to prevent or treat opportunistic infections

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Adler S, Cohen AH, Glassock RJ. Secondary glomerular diseases. In: Brenner BM, ed. Brenner & Rector's The Kidney. 5th ed. Philadelphia, Pa: WB Saunders;. 1996: 1519-24.
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• Anonymous. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 52-1993. A 17-year-old girl with massive hemoptysis and acute oliguric renal failure [clinical conference]. N Engl J Med. Dec 30 1993;329(27):2019-26. [Medline].
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• Lerner RA, Glassock RJ, Dixon FJ. The role of anti-glomerular basement membrane antibody in the pathogenesis of human glomerulonephritis. J Exp Med. Dec 1 1967;126(6):989-1004. [Medline]. [Full Text].
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• Levy JB, Turner AN, Rees AJ, et al. Long-term outcome of anti-glomerular basement membrane antibody disease treated with plasma exchange and immunosuppression. Ann Intern Med. Jun 5 2001;134(11):1033-42. [Medline].
• Miklovicova D, Cornelissen M, Cransberg K, et al. Etiology and epidemiology of end-stage renal disease in Dutch children 1987-2001. Pediatr Nephrol. Aug 2005;20(8):1136-42. [Medline].
• Rituxan (Rituximab) package insert. FDA approval date Feb 28, 2006. Genentech, Inc. South San Francisco, CA 94080.
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Article Last Updated: Jun 20, 2006