Goodpasture Syndrome Treatment & Management

  • Author: Pranay Kathuria, MD, MBBS, FACP, FASN, FNKH; Chief Editor: Vecihi Batuman, MD, FACP, FASN   more...
 
Updated: Nov 16, 2011
 

Approach Considerations

The 3 principles of therapy in anti–glomerular basement membrane (anti-GBM) disease are (1) to rapidly remove circulating antibody, primarily by plasmapheresis; (2) to stop further production of antibodies using immunosuppression with medications; and (3) to remove offending agents that may have initiated the antibody production.

The rapid institution of appropriate therapy depends on distinguishing anti-GBM disease from other pulmonary renal syndromes with similar presentations. Beginning therapy despite a pending or preliminary negative test result for serum anti-GBM antibodies may be necessary; a delay in this setting can be associated with adverse clinical outcomes.

Patients who develop massive hemoptysis or acute respiratory failure should be cared for in an ICU. Transfer to a hospital where plasmapheresis and/or hemodialysis is available may be necessary. Standard indications for dialysis are followed.

After hospital discharge, patients require long-term regular visits for monitoring of renal function and immunosuppressive therapy. If renal function does not return, dialysis is continued indefinitely and the patient should be referred for renal transplantation.

Patients receiving renal transplants must be informed that anti-GBM disease can recur in the transplanted kidney, although graft loss due to this is very rare.

Go to Pediatric Anti-GBM Disease (Goodpasture Syndrome) for complete information on this topic.

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Plasmapheresis

In published case series and one randomized trial, plasmapheresis has been shown to be beneficial in the treatment of Goodpasture syndrome by removal of anti-GBM antibodies. Plasmapheresis is generally instituted after the diagnosis of Goodpasture syndrome is established either by renal biopsy or by detection of anti-GBM antibodies.

When a patient presents in a life-threatening situation secondary to pulmonary hemorrhage, however, plasmapheresis may be initiated if the diagnosis appears very likely, even though confirmation is not available immediately.

The extent and duration of plasmapheresis is not known, but 4-liter plasma exchanges daily or every other day is usually performed. The plasmapheresis is continued for 2-3 weeks or until the patient's clinical course has improved and serum anti-GBM antibodies are not detected.

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Immunosuppressive Therapy

Immunosuppressive therapy is required to inhibit antibody production and rebound hypersynthesis, which may occur following discontinuation of plasma exchange.

Initial therapy includes cyclophosphamide at 2 mg/kg orally, adjusted to maintain a white blood cell count of approximately 5000, and corticosteroids (eg, prednisone at 1-1.5 mg/kg). Treatment of acute life-threatening alveolar hemorrhage in patients with Goodpasture syndrome is with pulse methylprednisolone at 1 g/day for 3 days, followed by a gradual corticosteroid taper. Intravenous cyclophosphamide is begun concomitantly at 1 g/m2 and repeated 3-4 weeks later, depending on the recovery of bone marrow.

The duration of immunosuppressive therapy is not well established. Anti-GBM antibody levels must be monitored at regular intervals. In patients who achieve a prompt remission, immunosuppression with cyclophosphamide is continued for 2-3 months and steroids for 6 months. Patients with clinically or serologically active disease at 3-4 months need longer immunosuppression (6-9 mo). Azathioprine may be substituted for cyclophosphamide to reduce adverse effects, especially in patients needing prolonged immunosuppression.

Pneumocystis jiroveci pneumonia has an annual incidence of 1% but is a potentially deadly complication of immunosuppressive therapy in patients with Goodpasture syndrome. Prophylaxis with trimethoprim-sulfamethoxazole (160 mg trimethoprim and 800 mg sulfamethoxazole 3 times per week) may be a cost-effective method of prolonging life in these patients.

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Relapse

The circulating antibodies clear within 8 weeks, but an early relapse (ie, within the first 2 mo) may occur when circulating antibodies are still present. This typically manifests as alveolar hemorrhage. The risk factors for relapse include infection, volume overload, and cigarette smoking. Late relapse has been documented only rarely.

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Renal Transplantation

Renal transplantation has been used for end-stage renal disease secondary to Goodpasture syndrome. Most transplant centers prefer to wait 6-12 months after serologic evidence indicates that anti-GBM antibodies have cleared before performing transplantation.

Many patients develop linear deposits of IgG along glomeruli of the renal allograft. However, this development does not cause histologic or functional damage to the transplanted kidney.

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Consultations

Consult a nephrologist for evaluation of the patient in regard to the differential diagnosis of the renal disease, indication for renal biopsy, requirement for hemodialysis or plasmapheresis, and therapeutic input.

Consult a pulmonologist for patients with significant hemoptysis or respiratory compromise because these patients may deteriorate very rapidly and require bronchoscopy and/or intubation.

A consultation with a vascular surgeon may be required for establishment of vascular access for hemodialysis or plasmapheresis.

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Contributor Information and Disclosures
Author

Pranay Kathuria, MD, MBBS, FACP, FASN, FNKH  Professor of Medicine, Director, Division of Nephrology and Hypertension, University of Oklahoma School of Community Medicine

Pranay Kathuria, MD, MBBS, FACP, FASN, FNKH is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Heart Association, American Society of Hypertension, American Society of Nephrology, and National Kidney Foundation

Disclosure: Nothing to disclose.

Coauthor(s)

Frazier T Stevenson, MD  Associate Professor of Clinical Medicine and Director of Education Development, University of California Davis School of Medicine

Disclosure: Nothing to disclose.

Sat Sharma, MD, FRCPC  Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St Boniface General Hospital

Sat Sharma, MD, FRCPC is a member of the following medical societies: American Academy of Sleep Medicine, American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Thoracic Society, Canadian Medical Association, Royal College of Physicians and Surgeons of Canada, Royal Society of Medicine, Society of Critical Care Medicine, and World Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FACP, FASN  Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology

Disclosure: Nothing to disclose.

Additional Contributors

Eleanor Lederer, MD Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation, and Phi Beta Kappa

Disclosure: Dept of Veterans Affairs Grant/research funds Research

James W Lohr, MD Professor, Department of Internal Medicine, Division of Nephrology, Fellowship Program Director, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

James W Lohr, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Nephrology, and Central Society for Clinical Research

Disclosure: Genzyme Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Mauro Verrelli, MD, FRCP(C), FACP Assistant Professor, Department of Medicine, Section of Nephrology, University of Manitoba, Canada

Mauro Verrelli, MD, FRCP(C), FACP is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Society of Nephrology, Canadian Medical Association, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

References
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  2. Donaghy M, Rees AJ. Cigarette smoking and lung haemorrhage in glomerulonephritis caused by autoantibodies to glomerular basement membrane. Lancet. Dec 17 1983;2(8364):1390-3. [Medline].

  3. Yang R, Cui Z, Zhao J, Zhao MH. The role of HLA-DRB1 alleles on susceptibility of Chinese patients with anti-GBM disease. Clin Immunol. Nov 2009;133(2):245-50. [Medline].

  4. Savage CO, Pusey CD, Bowman C, Rees AJ, Lockwood CM. Antiglomerular basement membrane antibody mediated disease in the British Isles 1980-4. Br Med J (Clin Res Ed). Feb 1 1986;292(6516):301-4. [Medline]. [Full Text].

  5. Shah MK, Hugghins SY. Characteristics and outcomes of patients with Goodpasture's syndrome. South Med J. Dec 2002;95(12):1411-8. [Medline].

  6. Weber MF, Andrassy K, Pullig O, Koderisch J, Netzer K. Antineutrophil-cytoplasmic antibodies and antiglomerular basement membrane antibodies in Goodpasture's syndrome and in Wegener's granulomatosis. J Am Soc Nephrol. Jan 1992;2(7):1227-34. [Medline].

  7. Collard HR, Schwarz MI. Diffuse alveolar hemorrhage. Clin Chest Med. Sep 2004;25(3):583-92, vii. [Medline].

  8. Zhao J, Yan Y, Cui Z, Yang R, Zhao MH. The immunoglobulin G subclass distribution of anti-GBM autoantibodies against rHalpha3(IV)NC1 is associated with disease severity. Hum Immunol. Jun 2009;70(6):425-9. [Medline].

  9. Sinico RA, Radice A, Corace C, Sabadini E, Bollini B. Anti-glomerular basement membrane antibodies in the diagnosis of Goodpasture syndrome: a comparison of different assays. Nephrol Dial Transplant. Feb 2006;21(2):397-401. [Medline].

  10. Yang R, Hellmark T, Zhao J, Cui Z, Segelmark M, Zhao MH, et al. Levels of epitope-specific autoantibodies correlate with renal damage in anti-GBM disease. Nephrol Dial Transplant. Jun 2009;24(6):1838-44. [Medline].

  11. Rutgers A, Slot M, van Paassen P. Coexistence of anti-glomerular basement membrane antibodies and myeloperoxidase-ANCAs in crescentic glomerulonephritis. Am J Kidney Dis. Aug 2005;46(2):253-62.

  12. Frankel SK, Cosgrove GP, Fischer A. Update in the diagnosis and management of pulmonary vasculitis. Chest. Feb 2006;129(2):452-65.

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Goodpasture syndrome. A 45-year-old man was admitted to the intensive care unit with respiratory failure secondary to massive hemoptysis and acute renal failure. The antiglomerular basement membrane antibodies were strongly positive. The autopsy showed consolidated lung from extensive bleeding, which led to asphyxiation.
Goodpasture syndrome. Close-up view of gross pathology in a 45-year-old man admitted to the intensive care unit with respiratory failure secondary to massive hemoptysis and acute renal failure. The antiglomerular basement membrane antibodies were strongly positive. The autopsy showed consolidated lung from extensive bleeding, which led to asphyxiation.
Cytoplasmic antineutrophilic cytoplasmic antibodies (c-ANCA), which can appear in Goodpasture syndrome, are also commonly observed in Wegener granulomatosis and other vasculitides.
Perinuclear antineutrophilic cytoplasmic antibodies (p-ANCA), which can appear in Goodpasture syndrome, are also observed in Churg-Strauss vasculitis and occasionally in Wegener granulomatosis.
This is a renal biopsy slide of a patient who presented with hemoptysis and hematuria. The renal biopsy revealed crescentic glomerulonephritis, which may be caused by systemic lupus erythematosus, vasculitis, or Goodpasture syndrome.
This image of direct immunofluorescence shows smooth linear staining of the basement membrane secondary to immunoglobulin G deposition. This confirms the diagnosis of Goodpasture syndrome. Image courtesy of K. Orr, MD.
Goodpasture syndrome. A 35-year-old man who previously smoked cigarettes heavily, developed massive hemoptysis. The blood work showed positive anti–glomerular basement membrane antibodies.
 
 
 
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