Rapidly Progressive Glomerulonephritis Treatment & Management

  • Author: James W Lohr, MD; Chief Editor: Vecihi Batuman, MD, FACP, FASN   more...
 
Updated: Mar 1, 2012
 

Medical Care

Therapy for ANCA-associated disease consists of a combination of corticosteroids and cyclophosphamide. Treatment with steroids alone results in a 3-fold increase in the risk of relapse compared to combination therapy. The only predictor of renal survival is the serum creatinine value at the time of diagnosis. Therefore, a high index of suspicion is imperative to establish the diagnosis quickly and to institute treatment as soon as possible. Renal failure requiring dialysis is not a contraindication to treatment. Many patients can be removed from dialysis for an extended period (18 mo to 2 y).

  • The regimen used by the Glomerular Disease Collaborative Network at the University of North Carolina at Chapel Hill[3, 4] is as follows:
    • Administer methylprednisolone at 7 mg/kg/d intravenously (not to exceed 1 g) for 3 days, followed by oral prednisone at 1 mg/kg/d (not to exceed 80 mg) for 3 weeks, and then oral prednisone at 2 mg/kg every other day (not to exceed 120 mg) for 3 months. This dose is decreased by 25% every 4 weeks until the patient stops taking prednisone.
    • Administer cyclophosphamide either intravenously or orally. Intravenous therapy is initially administered at a dose of 0.5 g/m2, and the oral dose is 2 mg/kg. Both are adjusted according to a 2-week leukocyte nadir count (goal 3000-4000/µL). The maximum intravenous dose is 1 g/m2. Oral and intravenous cyclophosphamide appears to be equally efficacious. However, this remains an area of controversy, particularly in the case of Wegener granulomatosis, for which some advocate oral therapy. The advantage to using the intravenous preparation is that the risk of cumulative toxicity is lower because a lower total dose is used.
  • Another protocol, which has been used widely and with success in Europe, is the substitution of azathioprine for cyclophosphamide after a 3-month induction period. Azathioprine is administered at 2 mg/kg orally in a single daily dose. This is continued for 6-12 months.
  • Methotrexate has been substituted for cyclophosphamide in the initial treatment of Wegener granulomatosis for mild disease and has been used for treatment after initial induction therapy with cyclophosphamide in more severe disease.[5]
  • Plasmapheresis may be a beneficial addition to therapy for patients who present with severe renal failure (serum creatinine >6 mg/dL) or those who progress despite treatment.
  • Rituximab may improve renal outcomes in antineutrophil cytoplasmic antibody–associated vasculitis; in addition to anti–B-cell therapy, therapy directed at T cells may improve renal outcome, according to a study conducted by Berden et al.[6]
  • Other medications have been used in an attempt to attain a remission, such as intravenous immunoglobulin, antithymocyte antibody, and humanized monoclonal antibody to CD4 and CD25. None of these therapies has been well studied. They appear in the literature as case reports.
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Consultations

Nephrology consultation should be obtained as early as possible in suspected cases of rapidly progressive glomerulonephritis.

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Contributor Information and Disclosures
Author

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: Alexion Salary Employment

Coauthor(s)

Kerry C Owens, MD  Consulting Staff, Department of Internal Medicine, Section of Nephrology, Integris Baptist Medical Center of Oklahoma City

Kerry C Owens, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, Oklahoma State Medical Association, and Sigma Xi

Disclosure: Nothing to disclose.

Specialty Editor Board

F John Gennari, MD  Associate Chair for Academic Affairs, Robert F and Genevieve B Patrick Professor, Department of Medicine, University of Vermont College of Medicine

F John Gennari, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Federation for Medical Research, American Heart Association, American Physiological Society, American Society for Clinical Investigation, American Society of Nephrology, and International Society of Nephrology

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

George R Aronoff, MD  Director, Professor, Departments of Internal Medicine and Pharmacology, Section of Nephrology, Kidney Disease Program, University of Louisville School of Medicine

George R Aronoff, MD is a member of the following medical societies: American Federation for Medical Research, American Society of Nephrology, Kentucky Medical Association, and National Kidney Foundation

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. Davies DJ, Moran JE, Niall JF, et al. Segmental necrotising glomerulonephritis with antineutrophil antibody: possible arbovirus aetiology?. Br Med J (Clin Res Ed). Aug 28-Sep 4 1982;285(6342):606. [Medline].

  2. Hall JB, Wadham BM, Wood CJ, et al. Vasculitis and glomerulonephritis: a subgroup with an antineutrophil cytoplasmic antibody. Aust N Z J Med. Jun 1984;14(3):277-8. [Medline].

  3. Falk RJ, Hogan S, Carey TS, et al. Clinical course of anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and systemic vasculitis. The Glomerular Disease Collaborative Network. Ann Intern Med. Nov 1 1990;113(9):656-63. [Medline].

  4. Nachman PH, Hogan SL, Jennette JC, et al. Treatment response and relapse in antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. J Am Soc Nephrol. Jan 1996;7(1):33-9. [Medline].

  5. Villa-Forte A, Clark TM, Gomes M, et al. Substitution of methotrexate for cyclophosphamide in Wegener granulomatosis: a 12-year single-practice experience. Medicine (Baltimore). Sep 2007;86(5):269-77. [Medline].

  6. Berden AE, Jones RB, Erasmus DD, et al. Tubular Lesions Predict Renal Outcome in Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis after Rituximab Therapy. J Am Soc Nephrol. Feb 2012;23(2):313-321. [Medline].

  7. Andrassy K, Kuster S, Waldherr R, et al. Rapidly progressive glomerulonephritis: analysis of prevalence and clinical course. Nephron. 1991;59(2):206-12. [Medline].

  8. Bacani RA, Velasquez F, Kanter A, et al. Rapidly progressive (nonstreptococcal) glomerulonephritis. Ann Intern Med. Sep 1968;69(3):463-85. [Medline].

  9. Couser WG. Rapidly progressive glomerulonephritis: classification, pathogenetic mechanisms, and therapy. Am J Kidney Dis. Jun 1988;11(6):449-64. [Medline].

  10. de Lind van Wijngaarden RA, Hauer HA, Wolterbeek R, et al. Chances of renal recovery for dialysis-dependent ANCA-associated glomerulonephritis. J Am Soc Nephrol. Jul 2007;18(7):2189-97. [Medline].

  11. Hogan SL, Nachman PH, Wilkman AS, et al. Prognostic markers in patients with antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. J Am Soc Nephrol. Jan 1996;7(1):23-32. [Medline].

  12. Hotta O, Ishida A, Kimura T, et al. Improvements in treatment strategies for patients with antineutrophil cytoplasmic antibody-associated rapidly progressive glomerulonephritis. Ther Apher Dial. Oct 2006;10(5):390-5. [Medline].

  13. Jayne DR, Gaskin G, Pusey CD, et al. ANCA and predicting relapse in systemic vasculitis. QJM. Feb 1995;88(2):127-33. [Medline].

  14. [Best Evidence] Jayne DR, Gaskin G, Rasmussen N, et al. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol. Jul 2007;18(7):2180-8. [Medline].

  15. Jennette JC. Renal involvement in systemic vasculilits. In: Jennette JC, Olson JL, Schwartz MM, Silva FG, eds. Hepinstall's Pathology of the Kidney. 5th ed. Philadelphia: Lippincott-Raven; 1998:1059-94.

  16. Pusey CD, Rees AJ, Evans DJ, et al. Plasma exchange in focal necrotizing glomerulonephritis without anti-GBM antibodies. Kidney Int. Oct 1991;40(4):757-63. [Medline].

  17. Savige J, Davies D, Falk RJ, et al. Antineutrophil cytoplasmic antibodies and associated diseases: a review of the clinical and laboratory features. Kidney Int. Mar 2000;57(3):846-62. [Medline].

  18. Stilmant MM, Bolton WK, Sturgill BC, et al. Crescentic glomerulonephritis without immune deposits: clinicopathologic features. Kidney Int. Feb 1979;15(2):184-95. [Medline].

 
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