Medical Care

Hospitalization is required for prompt diagnosis and treatment, close monitoring, and supportive care in patients with anti-glomerular basement membrane (GBM) antibody disease. Patients may initially require intensive care.

The therapeutic regimen depends on the patient's potential to respond.
- Patients with moderate glomerulonephritis (serum creatinine level < 5 mg/dL and crescents in < 50-75% of glomeruli) and patients with acute disease (brief illness, lack of chronicity on histology) are likely to respond to therapy. The treatment of choice consists of repeated plasmapheresis combined with glucocorticosteroids and cyclophosphamide.
- Patients with advanced disease (serum creatinine level >5 mg/dL and crescents in >75% of glomeruli) and histologic signs of chronicity are unlikely to improve with any therapy and should be spared the clinically significant risks of aggressive treatment. Supportive care and eventual renal transplantation are recommended.
- Patients who are antineutrophilic cytoplasmic antibody (ANCA) positive with clinical presentations consistent with vasculitis are likely to benefit from aggressive therapy independent of the severity of disease.^[11]
- Most patients with pulmonary hemorrhage respond rapidly to methylprednisolone pulses, plasma exchange, or plasmapheresis.
- Patients with mild renal disease who do not have pulmonary hemorrhage may be successfully treated with prednisone alone.
In patients with renal insufficiency, treatment should be commensurate with the severity of disease and includes therapy for hypertension, fluid overload, and electrolyte and acid-base imbalances.
Early plasmapheresis removes circulating anti-GBM antibodies and other mediators of inflammation and has been advocated as the treatment of choice.
- Plasmapheresis with immunosuppression is effective in the treatment of pulmonary hemorrhage and substantially improves renal function in patients with serum creatinine levels of less than 7 mg/dL or with crescents in less than 50% of the glomeruli.
- Therapy usually consists of 14 treatments during 2-3 weeks.
- Concomitant administration of cyclophosphamide and steroids is essential to prevent rebound antibody formation.
- Additional plasmapheresis may be required if anti-GBM antibody titers remain elevated after the treatments.
- Patients undergoing plasmapheresis who develop serious infections benefit from intravenous administration of immunoglobulins.
Rituximab, a chimeric monoclonal antibody targeting the pan B-cell marker CD20, has been used as an adjunctive or second-line therapy in resistant cases or whencyclophosphamide is contraindicated.^{[12, 13]} At present, there is insufficient evidence to recommend it as a first-line therapy for patients with anti-GBM antibody disease.
Experimental and future treatment
- Preliminary data suggest that removal of anti-GBM antibody by means of immunoadsorption may be beneficial in patients with Goodpasture disease. These results must be verified before immunoadsorption can be recommended.
  - A retrospective review of 10 anti-GBM patients treated with immunoadsorption reported a reduction in antibodies to negative levels in all patients by the first 9 immunoadsorption treatments and that renal survival was 40% at diagnosis, 70% after the end of immunoadsorption, and 63% after one year.^[14]
The effect of blocking CD28-B7, the costimulatory pathway for T-cell activation, was evaluated in a rat model of anti-GBM disease. The rationale for this attempt was the observation that T-cell–mediated mechanisms may play a direct role in the glomerular and alveolar injury that occurs in anti-GBM disease.

Surgical Care

See the list below:

In patients with irreversible renal failure, renal transplantation is usually deferred for at least 1 year to decrease the risk of recurrence.

Consultations

See the list below:

A nephrologist may be needed to manage glomerulonephritis and renal insufficiency.
A pulmonologist may be needed to manage pulmonary hemorrhage.
An intense care specialist may need to be consulted to treat critically ill patients.
A surgeon may need to be consulted to establish dialysis access and perform renal transplantation.

Diet

Dietary modifications for patients with renal insufficiency include the following:

Adjustments in fluid intake based on urine output
Eating foods with low levels of sodium and phosphate

Activity

See the list below:

Patients should avoid strenuous activity.

Medication

Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013 Jan. 65 (1):1-11. [Medline].
Kambham N. Crescentic Glomerulonephritis: An Update on Pauci-immune and Anti-GBM Diseases. Adv Anat Pathol. 2012 Mar. 19(2):111-24. [Medline].
Cui Z, Zhao MH. Advances in human antiglomerular basement membrane disease. Nat Rev Nephrol. 2011 Jul 19. 7(12):697-705. [Medline].
Ooi JD, Holdsworth SR, Kitching AR. Advances in the pathogenesis of Goodpasture's disease: from epitopes to autoantibodies to effector T cells. J Autoimmun. 2008 Nov. 31(3):295-300. [Medline].
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. 2011 Oct. 22(10):1946-52. [Medline]. [Full Text].
Zou J, Hannier S, Cairns LS, et al. Healthy individuals have Goodpasture autoantigen-reactive T cells. J Am Soc Nephrol. 2008 Feb. 19(2):396-404. [Medline]. [Full Text].
Wilson CB, Dixon FJ. Anti-glomerular basement membrane antibody-induced glomerulonephritis. Kidney Int. 1973 Feb. 3(2):74-89. [Medline].
Jennette JC. Rapidly progressive crescentic glomerulonephritis. Kidney Int. 2003 Mar. 63 (3):1164-77. [Medline].
Jais JP, Knebelmann B, Giatras I, et al. X-linked Alport syndrome: natural history in 195 families and genotype- phenotype correlations in males. J Am Soc Nephrol. 2000 Apr. 11(4):649-57. [Medline].
McAdoo SP, Pusey CD. Anti-Glomerular Basement Membrane Disease. Clin J Am Soc Nephrol. 2017 Jul 7. 12 (7):1162-1172. [Medline].
McAdoo SP, Tanna A, Hrušková Z, Holm L, Weiner M, Arulkumaran N, et al. Patients double-seropositive for ANCA and anti-GBM antibodies have varied renal survival, frequency of relapse, and outcomes compared to single-seropositive patients. Kidney Int. 2017 May 12. [Medline].
Syeda UA, Singer NG, Magrey M. Anti-glomerular basement membrane antibody disease treated with rituximab: A case-based review. Semin Arthritis Rheum. 2013 Jun. 42 (6):567-72. [Medline].
Gulati K, McAdoo SP. Anti-Glomerular Basement Membrane Disease. Rheum Dis Clin North Am. 2018 Nov. 44 (4):651-673. [Medline].
Biesenbach P, Kain R, Derfler K, Perkmann T, Soleiman A, Benharkou A, et al. Long-term outcome of anti-glomerular basement membrane antibody disease treated with immunoadsorption. PLoS One. 2014. 9 (7):e103568. [Medline].
Priest N, Roseby R, Waters E, et al. Family and carer smoking control programmes for reducing children's exposure to environmental tobacco smoke. Cochrane Database Syst Rev. 2008 Oct 8. CD001746. [Medline].
Bergs L. Goodpasture syndrome. Crit Care Nurse. 2005 Oct. 25(5):50-4, 56, 57-8. [Medline].
Bigler SA, Parry WM, Fitzwater DS, Baliga R. An 11-month-old with anti-glomerular basement membrane disease. Am J Kidney Dis. 1997 Nov. 30(5):710-2. [Medline].
Bolton WK. Goodpasture's syndrome. Kidney Int. 1996 Nov. 50(5):1753-66. [Medline].
Borza DB, Bondar O, Colon S, et al. Goodpasture autoantibodies unmask cryptic epitopes by selectively dissociatingautoantigen complexes lacking structural reinforcement: novel mechanisms for immune privilege and autoimmunepathogenesis. J Biol Chem. 2005 Jul 22. 280(29):27147-54.
Borza DB, Hudson BG. Molecular characterization of the target antigens of anti-glomerular basementmembrane antibody disease. Springer Semin Immunopathol. 2003 May. 24(4):345-61. [Medline].
Borza DB, Neilson EG, Hudson BG. Pathogenesis of Goodpasture syndrome: a molecular perspective. Semin Nephrol. 2003 Nov. 23(6):522-31. [Medline].
Boven K, Miljoen HP, Van Hoeck KJ, et al. Anti-glomerular basement membrane glomerulopathy in a young child. Pediatr Nephrol. 1996 Dec. 10(6):745-7. [Medline].
Brainwood D, Kashtan C, Gubler MC, Turner AN. Targets of alloantibodies in Alport anti-glomerular basement membrane disease after renal transplantation. Kidney Int. 1998 Mar. 53(3):762-6. [Medline]. [Full Text].
Brito MJ, Patricio A, Rolo P, et al. Anti-glomerular basement membrane nephritis in a 5-year-old girl. Pediatr Nephrol. 1997 Feb. 11(1):80-1. [Medline].
Burns AP, Fisher M, Li P, Pusey CD, Rees AJ. Molecular analysis of HLA class II genes in Goodpasture's disease. QJM. 1995 Feb. 88(2):93-100. [Medline].
Cairns LS, Phelps RG, Bowie L, Hall AM, Saweirs WW, Rees AJ. The fine specificity and cytokine profile of T-helper cells responsive to the alpha3 chain of type IV collagen in Goodpasture's disease. J Am Soc Nephrol. 2003 Nov. 14(11):2801-12. [Medline]. [Full Text].
Cole BR, Salinas-Madrigal L. Crescentic glomerulonephritis. Pediatric Nephrology. 4th ed. Baltimore, MD: Lippincott, Williams and Wilkins; 1999. 680-6.
Collard HR, Schwarz MI. Diffuse alveolar hemorrhage. Clin Chest Med. 2004 Sep. 25(3):583-92, vii.
Dean EG, Wilson GR, Li M, et al. Experimental autoimmune Goodpasture's disease: a pathogenetic role for botheffector cells and antibody in injury. Kidney Int. 2005 Feb. 67(2):566-75. [Medline].
Derk CT, Jimenez SA. Goodpasture-like syndrome induced by D-penicillamine in a patient with systemicsclerosis: report and review of the literature. J Rheumatol. 2003 Jul. 30(7):1616-20. [Medline].
Fonck C, Loute G, Cosyns JP, Pirson Y. Recurrent fulminant anti-glomerular basement membrane nephritis at a 7-year interval. Am J Kidney Dis. 1998 Aug. 32(2):323-7. [Medline].
Heeringa P, Schreiber A, Falk RJ, Jeannette JC. Pathogenesis of pulmonary vasculitis. Semin Respir Crit Care Med. 2004 Oct. 25(5):465-74. [Medline].
Hellmark T, Johansson C, Wieslander J. Characterization of anti-GBM antibodies involved in Goodpasture's syndrome. Kidney Int. 1994 Sep. 46(3):823-9. [Medline].
Hochegger K, Wolf D, Rosenkranz AR. CD4CD25 regulatory T cells: a new treatment option in glomerulonephritis. Kidney Int. 2005 Oct. 68(4):1898-9. [Medline].
Hudson BG, Tryggvason K, Sundaramoorthy M, Neilson EG. Alport's syndrome, Goodpasture's syndrome, and type IV collagen. N Engl J Med. 2003 Jun 19. 348(25):2543-56. [Medline].
Jara LJ, Vera-Lastra O, Calleja MC. Pulmonary-renal vasculitic disorders: differential diagnosis and management. Curr Rheumatol Rep. 2003 Apr. 5(2):107-15. [Medline].
Kalluri R, Wilson CB, Weber M, et al. Identification of the alpha 3 chain of type IV collagen as the common autoantigen in antibasement membrane disease and Goodpasture syndrome. J Am Soc Nephrol. 1995 Oct. 6(4):1178-85. [Medline].
Kitching AR, Holdsworth SR, Tipping PG. Crescentic glomerulonephritis--a manifestation of a nephritogenic Th1 response?. Histol Histopathol. 2000 Jul. 15(3):993-1003. [Medline].
Kotanko P, Pusey CD, Levy JB. Recurrent glomerulonephritis following renal transplantation. Transplantation. 1997 Apr 27. 63(8):1045-52. [Medline].
Laczika K, Knapp S, Derfler K, Soleiman A, Horl WH, Druml W. Immunoadsorption in Goodpasture's syndrome. Am J Kidney Dis. 2000 Aug. 36(2):392-5. [Medline].
Little MA, Pusey CD. Rapidly progressive glomerulonephritis: current and evolving treatment strategies. J Nephrol. 2004 Nov-Dec. 17 Suppl 8:S10-9.
Lou YH. Anti-GBM glomerulonephritis: a T cell-mediated autoimmune disease?. Arch Immunol Ther Exp (Warsz). 2004 Mar-Apr. 52(2):96-103. [Medline].
Madore F, Lazarus JM, Brady HR. Therapeutic plasma exchange in renal diseases [editorial]. J Am Soc Nephrol. 1996 Mar. 7(3):367-86. [Medline].
Meisels IS, Stillman IE, Kuhlik AB. Anti-glomerular basement membrane disease and dual positivity for antineutrophil cytoplasmic antibody in a patient with membranous nephropathy. Am J Kidney Dis. 1998 Oct. 32(4):646-8. [Medline].
Merkel F, Kalluri R, Marx M, et al. Autoreactive T-cells in Goodpasture's syndrome recognize the N-terminal NC1 domain on alpha 3 type IV collagen. Kidney Int. 1996 Apr. 49(4):1127-33. [Medline].
Netzer KO, Merkel F, Weber M. Goodpasture syndrome and end-stage renal failure--to transplant or not to transplant? [editorial]. Nephrol Dial Transplant. 1998 Jun. 13(6):1346-8. [Medline].
Phelps RG, Jones V, Turner AN, Rees AJ. Properties of HLA class II molecules divergently associated with Goodpasture's disease. Int Immunol. 2000 Aug. 12(8):1135-43. [Medline].
Phelps RG, Jones V, Turner AN, Rees AJ. Properties of HLA class II molecules divergently associated with Goodpasture's disease. Int Immunol. 2000 Aug. 12(8):1135-43. [Medline]. [Full Text].
Phelps RG, Rees AJ. The HLA complex in Goodpasture's disease: a model for analyzing susceptibility to autoimmunity. Kidney Int. 1999 Nov. 56(5):1638-53. [Medline].
Reynolds J, Khan SB, Allen AR, et al. Blockade of the CD154-CD40 costimulatory pathway prevents the development of experimental autoimmune glomerulonephritis. Kidney Int. 2004 Oct. 66(4):1444-52. [Medline].
Reynolds J, Norgan VA, Bhambra U, et al. Anti-CD8 monoclonal antibody therapy is effective in the prevention and treatmentof experimental autoimmune glomerulonephritis. J Am Soc Nephrol. 2002 Feb. 13(2):359-69. [Medline].
Reynolds J, Tam FW, Chandraker A. CD28-B7 blockade prevents the development of experimental autoimmune glomerulonephritis. J Clin Invest. 2000 Mar. 105(5):643-51. [Medline].
Salama AD, Chaudhry AN, Holthaus KA, et al. Regulation by CD25+ lymphocytes of autoantigen-specific T-cell responses in Goodpasture's (anti-GBM) disease. Kidney Int. 2003 Nov. 64(5):1685-94. [Medline].
Salama AD, Chaudhry AN, Holthaus KA, Mosley K, Kalluri R, Sayegh MH. Regulation by CD25+ lymphocytes of autoantigen-specific T-cell responses in Goodpasture's (anti-GBM) disease. Kidney Int. 2003 Nov. 64(5):1685-94. [Medline]. [Full Text].
Salama AD, Chaudhry AN, Ryan JJ, et al. In Goodpasture's disease, CD4(+) T cells escape thymic deletion and are reactive with the autoantigen alpha3(IV)NC1. J Am Soc Nephrol. 2001 Sep. 12(9):1908-15. [Medline].
Salama AD, Chaudhry AN, Ryan JJ, et al. In Goodpasture's disease, CD4(+) T cells escape thymic deletion and are reactive with the autoantigen alpha3(IV)NC1. J Am Soc Nephrol. 2001 Sep. 12(9):1908-15. [Medline]. [Full Text].
Salama AD, Pusey CD. Immunology of anti-glomerular basement membrane disease. Curr Opin Nephrol Hypertens. 2002 May. 11(3):279-86. [Medline].
Shah MK, Hugghins SY. Characteristics and outcomes of patients with Goodpasture's syndrome. South Med J. 2002 Dec. 95(12):1411-8. [Medline].
Srivastava A, Rao GK, Segal PE, Shah M, Geetha D. Characteristics and outcome of crescentic glomerulonephritis in patients with both antineutrophil cytoplasmic antibody and anti-glomerular basement membrane antibody. Clin Rheumatol. 2013 Sep. 32(9):1317-22. [Medline].
Turner AN. Antibodies: still important in anti-GBM disease. Nephron Clin Pract. 2003. 94(3):c51-2. [Medline].
Verburgh CA, Bruijn JA, Daha MR, van Es LA. Sequential development of anti-GBM nephritis and ANCA-associated Pauci- immune glomerulonephritis. Am J Kidney Dis. 1999 Aug. 34(2):344-8. [Medline].
Wang XP, Fogo AB, Colon S, Giannico G, Abul-Ezz SR, Miner JH. 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. 2005 Dec. 16(12):3563-71. [Medline]. [Full Text].
Wolf D, Hochegger K, Wolf AM, et al. CD4+CD25+ regulatory T cells inhibit experimental anti-glomerular basement membrane glomerulonephritis in mice. J Am Soc Nephrol. 2005 May. 16(5):1360-70. [Medline].
Wong D, Phelps RG, Turner AN. The Goodpasture antigen is expressed in the human thymus. Kidney Int. 2001 Nov. 60(5):1777-83. [Medline].
Xenocostas A, Jothy S, Collins B, et al. Anti-glomerular basement membrane glomerulonephritis after extracorporeal shock wave lithotripsy. Am J Kidney Dis. 1999 Jan. 33(1):128-32. [Medline].
Yamaguchi H, Shirakami A, Haku T, Taoka T, Nakanishi Y, Inai T, et al. Pulmonary-Renal Syndrome with Negative ANCAs and Anti-GBM Antibody. Case Rep Nephrol. 2013. 2013:434531. [Medline]. [Full Text].
Yang R, Cui Z, Hellmark T, Segelmark M, Zhao MH, Wang HY. Natural anti-GBM antibodies from normal human sera recognize alpha3(IV)NC1 restrictively and recognize the same epitopes as anti-GBM antibodies from patients with anti-GBM disease. Clin Immunol. 2007 Aug. 124(2):207-12. [Medline]. [Full Text].
Yoshioka K, Iseki T, Okada M, Morimoto Y, Eryu N, Maki S. Identification of Goodpasture antigens in human alveolar basement membrane. Clin Exp Immunol. 1988 Dec. 74(3):419-24. [Medline].
Zou J, Henderson L, Thomas V, Swan P, Turner AN, Phelps RG. Presentation of the Goodpasture autoantigen requires proteolytic unlocking steps that destroy prominent T cell epitopes. J Am Soc Nephrol. 2007 Mar. 18(3):771-9. [Medline]. [Full Text].
Canney M, O'Hara PV, McEvoy CM, Medani S, Connaughton DM, Abdalla AA, et al. Spatial and Temporal Clustering of Anti-Glomerular Basement Membrane Disease. Clin J Am Soc Nephrol. 2016 Aug 8. 11 (8):1392-9. [Medline].
Reich EP, Sherwin RS, Kanagawa O, Janeway CA Jr. An explanation for the protective effect of the MHC class II I-E molecule in murine diabetes. Nature. 1989 Sep 28. 341 (6240):326-8. [Medline].
Canney M, O'Hara PV, McEvoy CM, Medani S, Connaughton DM, Abdalla AA, et al. Spatial and Temporal Clustering of Anti-Glomerular Basement Membrane Disease. Clin J Am Soc Nephrol. 2016 Aug 8. 11 (8):1392-9. [Medline].

Media Gallery

Immunofluorescence staining for immunoglobulin (IgG) reveals diffuse, high-intensity, linear staining of the glomerular basement membrane in a patient with anti–glomerular basement membrane (GBM) disease. Courtesy of Glen Markowitz, MD, Department of Pathology, Columbia University.

of 1

Author

Agnieszka Swiatecka-Urban, MD, FASN, FAAP Associate Professor, Department of Pediatrics, Cell Biology and Physiology, University of Pittsburgh School of Medicine; Assistant Professor, Department of Nephrology, Children's Hospital of Pittsburgh

Agnieszka Swiatecka-Urban, MD, FASN, FAAP is a member of the following medical societies: American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology

Disclosure: Nothing to disclose.

Coauthor(s)

Prasad Devarajan, MD, FAAP Louise M Williams Endowed Chair in Pediatrics, Professor of Pediatrics and Developmental Biology, Director of Nephrology and Hypertension, Director of the Nephrology Fellowship Program, Medical Director of the Kidney Stone Center, Co-Director of the Institutional Office of Pediatric Clinical Fellowships, Director of Clinical Nephrology Laboratory, CEO of Dialysis Unit, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine

Prasad Devarajan, MD, FAAP is a member of the following medical societies: American Heart Association, American Society of Nephrology, American Society of Pediatric Nephrology, National Kidney Foundation, Society for Pediatric Research

Disclosure: Received none from Coinventor on patents submitted for the use of NGAL as a biomarker of kidney injury for none.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Adrian Spitzer, MD Clinical Professor Emeritus, Department of Pediatrics, Albert Einstein College of Medicine

Adrian Spitzer, MD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Medical Research, American Pediatric Society, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Craig B Langman, MD The Isaac A Abt, MD, Professor of Kidney Diseases, Northwestern University, The Feinberg School of Medicine; Division Head of Kidney Diseases, The Ann and Robert H Lurie Children's Hospital of Chicago

Craig B Langman, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, International Society of Nephrology

Disclosure: Received income in an amount equal to or greater than $250 from: Alexion Pharmaceuticals; Horizon Pharmaceuticals); ; Dicerna Pharmaceuticals<br/>Incyte Pharmaceuticals; Eli Lilly for: Federation bio.

Additional Contributors

Uri S Alon, MD Director of Bone and Mineral Disorders Clinic and Renal Research Laboratory, Children's Mercy Hospital of Kansas City; Professor, Department of Pediatrics, Division of Pediatric Nephrology, University of Missouri-Kansas City School of Medicine

Uri S Alon, MD is a member of the following medical societies: American Federation for Medical Research

Disclosure: Nothing to disclose.