Antiglomerular Basement Membrane Disease Clinical Presentation

  • Author: Ramesh Saxena, MD, PhD; Chief Editor: Vecihi Batuman, MD, FACP, FASN   more...
 
Updated: Nov 21, 2011
 

History

Patients with anti-GBM nephritis can present with glomerulonephritis alone or with accompanying pulmonary hemorrhage.[3] Although pulmonary hemorrhage may be minor, it is often severe and life threatening. Pulmonary hemorrhage occurs more frequently in young adult males, whereas anti-GBM nephritis without lung involvement tends to occur more frequently in women in their seventh decade of life.

The disease may begin with either renal or pulmonary manifestations. Usually, both organs are involved more or less simultaneously. However, in several cases, the interval to the second organ's involvement may be prolonged up to a year.

  • Prodromal period
    • In 25-30% of patients, a prodromal period of flulike illness occurs.
    • In approximately 5% of patients, arthralgia, myalgia, and arthritis are prominent features.
  • Pulmonary manifestations
    • The onset of pulmonary hemorrhage may be insidious, with symptoms such as anemia, pallor, weakness, lethargy, dyspnea upon exertion, and, sometimes, dry cough.
    • In some cases, onset is acute and includes fever, massive hemoptysis, acute respiratory failure, asphyxia, and death; however, in many cases, the symptoms, including hemoptysis, dyspnea, cough, fever, tachycardia, and fatigue, may be present intermittently for weeks to months before the diagnosis is established.
  • Renal manifestations
    • The patient usually presents with an abrupt onset of oliguria or anuria. Hematuria or the passage of tea-colored urine is usually observed.
    • Rarely, the patient's renal involvement is more insidious in onset and he or she remains asymptomatic, progressing slowly until the development of uremic symptoms.
Next

Physical

  • Physical examination in the acute stage of the disease reveals respiratory distress, tachycardia, and cyanosis.
  • The patient usually appears pale because of anemia.
  • In severe cases, the patient may be in hemorrhagic shock and in respiratory failure, thus requiring volume resuscitation and ventilatory support, respectively.
  • Chest examination may reveal fine rales and dullness to percussion over the affected lung areas.
Previous
Next

Causes

The disease is caused by autoantibodies directed against the NC1 domain of the alpha-3 chain of type IV collagen.

  • Genetic susceptibility
    • Anti-GBM disease shows a strong association with HLA-DR2.
    • Further molecular genetics studies of HLA-DR2 reveal that the association of anti-GBM nephritis is with HLA-DRB1 alleles (HLA-DRB1 1501 and 1502 alleles), HLA-DQA1 01 alleles, and HLA-DQB1 06 alleles.
    • Anti-GBM nephritis is major histocompatibility complex–restricted. HLA-DRB1*1501 and 1502 alleles increase the susceptibility, while HLA-DR1 and HLA-DR7 are protective.
  • Environmental factors
    • A number of studies suggest a strong association between pulmonary hemorrhage and smoking.
    • Pulmonary hemorrhage may also be associated with exposure to hydrocarbons or other agents (eg, respiratory pathogens).
Previous
Proceed to Differential Diagnoses
 
 
Contributor Information and Disclosures
Author

Ramesh Saxena, MD, PhD  Associate Professor, Department of Internal Medicine, Division of Nephrology, University of Texas Southwestern Medical Center

Ramesh Saxena, MD, PhD is a member of the following medical societies: American Medical Association, American Society of Nephrology, International Society of Nephrology, and National Kidney Foundation

Disclosure: e-medicine Honoraria authoring review articles

Specialty Editor Board

Chike Magnus Nzerue, MD  Associate Dean for Clinical Affairs, Vice-Chairman of Internal Medicine, Meharry Medical College

Chike Magnus Nzerue, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Society of Nephrology, and National Kidney Foundation

Disclosure: Nothing to disclose.

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

Christie P Thomas, MBBS, FRCP, FASN, FAHA  Professor, Department of Internal Medicine, Division of Nephrology, Medical Director, Kidney and Kidney/Pancreas Transplant Program, University of Iowa Hospitals and Clinics

Christie P Thomas, MBBS, FRCP, FASN, FAHA is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Heart Association, American Society of Nephrology, American Society of Transplantation, American Thoracic Society, International Society of Nephrology, and Royal College of Physicians

Disclosure: Nothing to disclose.

Rebecca J Schmidt, DO, FACP, FASN  Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine

Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association

Disclosure: Renal Ventures Ownership interest Other

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.

References

  1. 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].

  2. Olson SW, Arbogast CB, Baker TP, Owshalimpur D, Oliver DK, Abbott KC, et al. Asymptomatic autoantibodies associate with future anti-glomerular basement membrane disease. J Am Soc Nephrol. Oct 2011;22(10):1946-52. [Medline].

  3. Sanders JS, Rutgers A, Stegeman CA, Kallenberg CG. Pulmonary: renal syndrome with a focus on anti-GBM disease. Semin Respir Crit Care Med. Jun 2011;32(3):328-34. [Medline].

  4. Sinico RA, Radice A, Corace C, et al. 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].

  5. Cui Z, Zhao J, Jia XY, Zhu SN, Jin QZ, Cheng XY, et al. Anti-glomerular basement membrane disease: outcomes of different therapeutic regimens in a large single-center chinese cohort study. Medicine (Baltimore). Sep 2011;90(5):303-11. [Medline].

  6. Cui Z, Zhao MH. Advances in human antiglomerular basement membrane disease. Nat Rev Nephrol. Jul 19 2011;[Medline].

  7. Lockwood CM, Rees AJ, Pearson TA, et al. Immunosuppression and plasma-exchange in the treatment of Goodpasture's syndrome. Lancet. Apr 3 1976;1(7962):711-5. [Medline].

  8. Wang XP, Fogo AB, Colon S, et al. Distinct epitopes for anti-glomerular basement membrane alport alloantibodies and goodpasture autoantibodies within the noncollagenous domain of alpha3(IV) collagen: a janus-faced antigen. J Am Soc Nephrol. Dec 2005;16(12):3563-71. [Medline].

  9. Kashtan CE. Renal transplantation in patients with Alport syndrome. Pediatr Transplant. Sep 2006;10(6):651-7. [Medline].

  10. Borza DB, Bondar O, Colon S, et al. Goodpasture autoantibodies unmask cryptic epitopes by selectively dissociating autoantigen complexes lacking structural reinforcement: novel mechanisms for immune privilege and autoimmune pathogenesis. J Biol Chem. Jul 22 2005;280(29):27147-54. [Medline].

  11. Borza DB. Autoepitopes and alloepitopes of type IV collagen: role in the molecular pathogenesis of anti-GBM antibody glomerulonephritis. Nephron Exp Nephrol. 2007;106(2):e37-43. [Medline]. [Full Text].

  12. Butkowski RJ, Langeveld JP, Wieslander J, et al. Localization of the Goodpasture epitope to a novel chain of basement membrane collagen. J Biol Chem. Jun 5 1987;262(16):7874-7. [Medline].

  13. Bygren P, Freiburghaus C, Lindholm T, et al. Goodpasture's syndrome treated with staphylococcal protein A immunoadsorption. Lancet. Dec 7 1985;2(8467):1295-6. [Medline].

  14. Cameron JS. Recurrent renal disease after renal transplantation. Curr Opin Nephrol Hypertens. Nov 1994;3(6):602-7. [Medline].

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

  16. Goodpasture EW. The significance of certain pulmonary lesions in relation to the etiology of influenza. Am J Med Sci. 1919;158:863-70.

  17. Gunnarsson A, Hellmark T, Wieslander J. Molecular properties of the Goodpasture epitope. J Biol Chem. Oct 6 2000;275(40):30844-8. [Medline].

  18. Hudson BG. The molecular basis of Goodpasture and Alport syndromes: beacons for the discovery of the collagen IV family. J Am Soc Nephrol. Oct 2004;15(10):2514-27. [Medline].

  19. Hudson BG, Tryggvason K, Sundaramoorthy M, et al. Alport's syndrome, Goodpasture's syndrome, and type IV collagen. N Engl J Med. Jun 19 2003;348(25):2543-56. [Medline].

  20. Hudson BG, Wieslander J, Wisdom BJ Jr, et al. Goodpasture syndrome: molecular architecture and function of basement membrane antigen. Lab Invest. Sep 1989;61(3):256-69. [Medline].

  21. Jung C, Karpouzas G, Stringer WW. Dyspnea, hemoptysis, and perihilar infiltrates in a 35-year-old man. Chest. Apr 2005;127(4):1437-41. [Medline].

  22. Khandelwal M, McCormick BB, Lajoie G, et al. Recurrence of anti-GBM disease 8 years after renal transplantation. Nephrol Dial Transplant. Feb 2004;19(2):491-4. [Medline].

  23. Larsson LA, Freiburghaus C, Nilsson IM. Plasma regeneration system for extensive immunoadsorption. Prog Artificial Organs. 1985;902-4.

  24. Levy JB, Hammad T, Coulthart A, et al. Clinical features and outcome of patients with both ANCA and anti-GBM antibodies. Kidney Int. Oct 2004;66(4):1535-40. [Medline].

  25. 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].

  26. Mathew TH. Recurrence of disease following renal transplantation. Am J Kidney Dis. Aug 1988;12(2):85-96. [Medline].

  27. Miner JH. Renal basement membrane components. Kidney Int. Dec 1999;56(6):2016-24. [Medline].

  28. Pirson Y, Goffin E, Squiffet JP. Outcome of anti-GBM nephritis after renal transplantation [abstract]. J Am Soc Nephrol. 1993;4:955.

  29. Reynolds J, Moss J, Duda MA, et al. The evolution of crescentic nephritis and alveolar haemorrhage following induction of autoimmunity to glomerular basement membrane in an experimental model of Goodpasture's disease. J Pathol. May 2003;200(1):118-29. [Medline].

  30. Saus J, Wieslander J, Langeveld JP, et al. Identification of the Goodpasture antigen as the alpha 3(IV) chain of collagen IV. J Biol Chem. Sep 15 1988;263(26):13374-80. [Medline].

  31. Saxena R, Bygren P, Butkowski R, et al. Specificity of kidney-bound antibodies in Goodpasture's syndrome. Clin Exp Immunol. Oct 1989;78(1):31-6. [Medline].

  32. Saxena R, Isaksson B, Bygren P, et al. A rapid assay for circulating anti-glomerular basement membrane antibodies in Goodpasture syndrome. J Immunol Methods. Mar 10 1989;118(1):73-8. [Medline].

  33. Short AK, Esnault VL, Lockwood CM. ANCA and anti-GBM antibodies in RPGN. Adv Exp Med Biol. 1993;336:441-4. [Medline].

  34. Simpson IJ, Doak PB, Williams LC, et al. Plasma exchange in Goodpasture's syndrome. Am J Nephrol. 1982;2(6):301-11. [Medline].

  35. Sinico RA, Radice A, Corace C, et al. 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].

  36. Stanton MC, Tange JD. Goodpasture's syndrome (pulmonary haemorrhage associated with glomerulonephritis). Australas Ann Med. May 1958;7(2):132-44. [Medline].

  37. Wang XP, Fogo AB, Colon S, et al. Distinct epitopes for anti-glomerular basement membrane alport alloantibodies and goodpasture autoantibodies within the noncollagenous domain of alpha3(IV) collagen: a janus-faced antigen. J Am Soc Nephrol. Dec 2005;16(12):3563-71. [Medline].

  38. Wieslander J, Bygren P, Heinegård D. Isolation of the specific glomerular basement membrane antigen involved in Goodpasture syndrome. Proc Natl Acad Sci U S A. Mar 1984;81(5):1544-8. [Medline].

  39. Wu J, Arends J, Borillo J, et al. A self T cell epitope induces autoantibody response: mechanism for production of antibodies to diverse glomerular basement membrane antigens. J Immunol. Apr 1 2004;172(7):4567-74. [Medline].

 
Previous
Next
 
Light microscopy of kidney biopsy specimen from a patient with antiglomerular basement membrane nephritis showing extensive crescent formation and the collapse of glomerular tuft.
Immunofluorescent examination of a kidney biopsy specimen from a patient with antiglomerular basement membrane nephritis showing a linear deposition of immunoglobulin G along the glomerular basement membrane.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.