Diagnostic Considerations

When evaluating a patient with suspected membranoproliferative glomerulonephritis (MPGN), also consider conditions such as postinfectious glomerulonephritis, fibrillary glomerulonephritis, immunoglobulin A (IgA) nephropathy, and vasculitis. In addition, recurrent MPGN needs to be differentiated from transplant glomerulopathy, which has a similar histology but lacks immune deposits.

Differential Diagnoses

Workup

Sethi S, Fervenza FC. Membranoproliferative glomerulonephritis--a new look at an old entity. N Engl J Med. 2012 Mar 22. 366(12):1119-31. [QxMD MEDLINE Link].
Lorenz EC, Sethi S, Leung N, Dispenzieri A, Fervenza FC, Cosio FG. Recurrent membranoproliferative glomerulonephritis after kidney transplantation. Kidney Int. 2010 Apr. 77(8):721-8. [QxMD MEDLINE Link].
Appel GB. Membranoprolferative glomerulonephritis - mechanisms and treatment. Contrib Nephrol. 2013. 181:163-74. [QxMD MEDLINE Link].
Smith KD, Alpers CE. Pathogenic mechanisms in membranoproliferative glomerulonephritis. Curr Opin Nephrol Hypertens. 2005 Jul. 14(4):396-403. [QxMD MEDLINE Link].
Garam N, Prohászka Z, Szilágyi Á, et al. C4 nephritic factor in patients with immune-complex-mediated membranoproliferative glomerulonephritis and C3-glomerulopathy. Orphanet J Rare Dis. 2019 Nov 8. 14 (1):247. [QxMD MEDLINE Link]. [Full Text].
Varade WS, Forristal J, West CD. Patterns of complement activation in idiopathic membranoproliferative glomerulonephritis, types I, II, and III. Am J Kidney Dis. 1990 Sep. 16(3):196-206. [QxMD MEDLINE Link].
Levy Y, George J, Yona E, et al. Partial lipodystrophy, mesangiocapillary glomerulonephritis, and complement dysregulation. An autoimmune phenomenon. Immunol Res. 1998 Aug. 18(1):55-60. [QxMD MEDLINE Link].
Walker PD. Dense deposit disease: new insights. Curr Opin Nephrol Hypertens. 2007 May. 16(3):204-12. [QxMD MEDLINE Link].
Licht C, Schlötzer-Schrehardt U, Kirschfink M, et al. MPGN II--genetically determined by defective complement regulation?. Pediatr Nephrol. 2007 Jan. 22(1):2-9. [QxMD MEDLINE Link].
Sethi S, Fervenza FC, Zhang Y, Zand L, Vrana JA, Nasr SH. C3 glomerulonephritis: clinicopathological findings, complement abnormalities, glomerular proteomic profile, treatment, and follow-up. Kidney Int. 2012 Aug. 82(4):465-73. [QxMD MEDLINE Link].
Sethi S, Nester CM, Smith RJ. Membranoproliferative glomerulonephritis and C3 glomerulopathy: resolving the confusion. Kidney Int. 2012 Mar. 81(5):434-41. [QxMD MEDLINE Link].
Nargund P, Kambham N, Mehta K, Lafayette RA. Clinicopathological features of membranoproliferative glomerulonephritis under a new classification. Clin Nephrol. 2015 Dec. 84 (12):323-30. [QxMD MEDLINE Link].
Neary JJ, Conlon PJ, Croke D, et al. Linkage of a gene causing familial membranoproliferative glomerulonephritis type III to chromosome 1. J Am Soc Nephrol. 2002 Aug. 13(8):2052-7. [QxMD MEDLINE Link].
Izzedine H, Sene D, Cacoub P, et al. Kidney diseases in HIV/HCV-co-infected patients. AIDS. 2009 Jun 19. 23(10):1219-26. [QxMD MEDLINE Link].
Hiramatsu R, Hoshino J, Suwabe T, Sumida K, Hasegawa E, Yamanouchi M, et al. Membranoproliferative glomerulonephritis and circulating cryoglobulins. Clin Exp Nephrol. 2013 May 31. [QxMD MEDLINE Link].
Tang SC, Lai KN. Hepatitis C virus-associated glomerulonephritis. Contrib Nephrol. 2013. 181:194-206. [QxMD MEDLINE Link].
Cansick JC, Lennon R, Cummins CL, et al. Prognosis, treatment and outcome of childhood mesangiocapillary (membranoproliferative) glomerulonephritis. Nephrol Dial Transplant. 2004 Nov. 19(11):2769-77. [QxMD MEDLINE Link].
Cameron JS, Turner DR, Heaton J, et al. Idiopathic mesangiocapillary glomerulonephritis. Comparison of types I and II in children and adults and long-term prognosis. Am J Med. 1983 Feb. 74(2):175-92. [QxMD MEDLINE Link].
O'Shaughnessy MM, Montez-Rath ME, Lafayette RA, Winkelmayer WC. Differences in initial treatment modality for end-stage renal disease among glomerulonephritis subtypes in the USA. Nephrol Dial Transplant. 2015 Nov 25. [QxMD MEDLINE Link].
Iitaka K, Moriya S, Nakamura S, et al. Long-term follow-up of type III membranoproliferative glomerulonephritis in children. Pediatr Nephrol. 2002 May. 17(5):373-8. [QxMD MEDLINE Link].
Anders D, Agricola B, Sippel M, et al. Basement membrane changes in membranoproliferative glomerulonephritis. II. Characterization of a third type by silver impregnation of ultra thin sections. Virchows Arch A Pathol Anat Histol. 1977 Oct 27. 376(1):1-19. [QxMD MEDLINE Link].
Braun MC, West CD, Strife CF. Differences between membranoproliferative glomerulonephritis types I and III in long-term response to an alternate-day prednisone regimen. Am J Kidney Dis. 1999 Dec. 34(6):1022-32. [QxMD MEDLINE Link].
Wilson GJ, Cho Y, Teixiera-Pinto A, Isbel N, Campbell S, Hawley C, et al. Long-term outcomes of patients with end-stage kidney disease due to membranoproliferative glomerulonephritis: an ANZDATA registry study. BMC Nephrol. 2019 Nov 21. 20 (1):417. [QxMD MEDLINE Link]. [Full Text].
Kawasaki Y, Kanno S, Ono A, Suzuki Y, Ohara S, Sato M, et al. Differences in clinical findings, pathology, and outcomes between C3 glomerulonephritis and membranoproliferative glomerulonephritis. Pediatr Nephrol. 2016 Jul. 31 (7):1091-9. [QxMD MEDLINE Link].
Masai R, Wakui H, Komatsuda A, et al. Characteristics of proliferative glomerulo-nephritis with monoclonal IgG deposits associated with membranoproliferative features. Clin Nephrol. 2009 Jul. 72(1):46-54. [QxMD MEDLINE Link].
Nasr SH, Satoskar A, Markowitz GS, et al. Proliferative glomerulonephritis with monoclonal IgG deposits. J Am Soc Nephrol. 2009 Sep. 20(9):2055-64. [QxMD MEDLINE Link]. [Full Text].
D'Amico G, Fornasieri A. Cryoglobulinemic glomerulonephritis: a membranoproliferative glomerulonephritis induced by hepatitis C virus. Am J Kidney Dis. 1995 Mar. 25(3):361-9. [QxMD MEDLINE Link].
Daghestani L, Pomeroy C. Renal manifestations of hepatitis C infection. Am J Med. 1999 Mar. 106(3):347-54. [QxMD MEDLINE Link].
[Guideline] Kidney Disease Improving Global Outcomes. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. KDIGO. Available at https://kdigo.org/guidelines/ckd-evaluation-and-management/. Accessed: December 17, 2019.
Arikan H, Koc M, Cakalagaoglu F, et al. Histopathological changes and tumour necrosis factor-alpha, transforming growth factor-beta and tenascin expression in patients with primary type I membranoproliferative glomerulonephritis in remission. Nephrology (Carlton). 2009 Apr. 14(2):219-26. [QxMD MEDLINE Link].
Jungers P, Chauveau D. Pregnancy in renal disease. Kidney Int. 1997 Oct. 52(4):871-85. [QxMD MEDLINE Link].
Jones G, Juszczak M, Kingdon E, et al. Treatment of idiopathic membranoproliferative glomerulonephritis with mycophenolate mofetil and steroids. Nephrol Dial Transplant. 2004 Dec. 19(12):3160-4. [QxMD MEDLINE Link].
Smith RJ, Alexander J, Barlow PN, et al. New approaches to the treatment of dense deposit disease. J Am Soc Nephrol. 2007 Sep. 18(9):2447-56. [QxMD MEDLINE Link].
Tarshish P, Bernstein J, Tobin JN, et al. Treatment of mesangiocapillary glomerulonephritis with alternate-day prednisone--a report of the International Study of Kidney Disease in Children. Pediatr Nephrol. 1992 Mar. 6(2):123-30. [QxMD MEDLINE Link].
Harmankaya O, Basturk T, Ozturk Y, Karabiber N, Obek A. Effect of acetylsalicylic acid and dipyridamole in primary membranoproliferative glomerulonephritis type I. Int Urol Nephrol. 2001. 33(3):583-7. [QxMD MEDLINE Link].
Faedda R, Satta A, Tanda F, Pirisi M, Bartoli E. Immunosuppressive treatment of membranoproliferative glomerulonephritis. Nephron. 1994. 67(1):59-65. [QxMD MEDLINE Link].
Cattran DC, Cardella CJ, Roscoe JM, et al. Results of a controlled drug trial in membranoproliferative glomerulonephritis. Kidney Int. 1985 Feb. 27(2):436-41. [QxMD MEDLINE Link].
Bruchfeld A, Lindahl K, Stahle L, et al. Interferon and ribavirin treatment in patients with hepatitis C-associated renal disease and renal insufficiency. Nephrol Dial Transplant. 2003 Aug. 18(8):1573-80. [QxMD MEDLINE Link].
Bagheri N, Nemati E, Rahbar K, Nobakht A, Einollahi B, Taheri S. Cyclosporine in the treatment of membranoproliferative glomerulonephritis. Arch Iran Med. 2008 Jan. 11(1):26-9. [QxMD MEDLINE Link].
Bhat P, Weiss S, Appel GB, Radhakrishnan J. Rituximab treatment of dysproteinemias affecting the kidney: a review of three cases. Am J Kidney Dis. 2007 Oct. 50(4):641-4. [QxMD MEDLINE Link].
Vilayur E, Trevillian P, Walsh M. Monoclonal gammopathy and glomerulopathy associated with chronic lymphocytic leukemia. Nat Clin Pract Nephrol. 2009 Jan. 5(1):54-8. [QxMD MEDLINE Link].
Guiard E, Karras A, Plaisier E, Duong Van Huyen JP, Fakhouri F, Rougier JP. Patterns of noncryoglobulinemic glomerulonephritis with monoclonal Ig deposits: correlation with IgG subclass and response to rituximab. Clin J Am Soc Nephrol. 2011 Jul. 6(7):1609-16. [QxMD MEDLINE Link].
Dillon JJ, Hladunewich M, Haley WE, Reich HN, Cattran DC, Fervenza FC. Rituximab therapy for Type I membranoproliferative glomerulonephritis. Clin Nephrol. 2012 Apr. 77(4):290-5. [QxMD MEDLINE Link].
Ruggenenti P, Daina E, Gennarini A, Carrara C, Gamba S, Noris M, et al. C5 Convertase Blockade in Membranoproliferative Glomerulonephritis: A Single-Arm Clinical Trial. Am J Kidney Dis. 2019 Aug. 74 (2):224-238. [QxMD MEDLINE Link].
Misiani R, Bellavita P, Fenili D, et al. Interferon alfa-2a therapy in cryoglobulinemia associated with hepatitis C virus. N Engl J Med. 1994 Mar 17. 330(11):751-6. [QxMD MEDLINE Link].
Pippias M, Stel VS, Aresté-Fosalba N, Couchoud C, Fernandez-Fresnedo G, Finne P, et al. Long-term Kidney Transplant Outcomes in Primary Glomerulonephritis: Analysis From the ERA-EDTA Registry. Transplantation. 2015 Nov 19. [QxMD MEDLINE Link].
Appel GB, Cook HT, Hageman G, et al. Membranoproliferative glomerulonephritis type II (dense deposit disease): an update. J Am Soc Nephrol. 2005 May. 16(5):1392-403. [QxMD MEDLINE Link].
Garini G, Allegri L, Vaglio A, et al. Hepatitis C virus-related cryoglobulinemia and glomerulonephritis: pathogenesis and therapeutic strategies. Ann Ital Med Int. 2005 Apr-Jun. 20(2):71-80. [QxMD MEDLINE Link].
Hanko JB, Mullan RN, O'Rourke DM, et al. The changing pattern of adult primary glomerular disease. Nephrol Dial Transplant. 2009 Oct. 24(10):3050-4. [QxMD MEDLINE Link].
Javaugue V, Karras A, Glowacki F, McGregor B, Lacombe C, Goujon JM, et al. Long-term Kidney Disease Outcomes in Fibrillary Glomerulonephritis: A Case Series of 27 Patients. Am J Kidney Dis. 2013 Jun 4. [QxMD MEDLINE Link].
Skerka C, Licht C, Mengel M, et al. Autoimmune forms of thrombotic microangiopathy and membranoproliferative glomerulonephritis: Indications for a disease spectrum and common pathogenic principles. Mol Immunol. 2009 Sep. 46(14):2801-7. [QxMD MEDLINE Link].

Media Gallery

Membranoproliferative glomerulonephritis (MPGN) type I. Glomerulus with lobular accentuation from increased mesangial cellularity. A segmental increase occurs in the mesangial matrix, and the peripheral capillary walls are thickened (hematoxylin and eosin stained section; original magnification × 250). Courtesy of John A. Minielly, MD.
Membranoproliferative glomerulonephritis (MPGN) type I. Electron microscopy of prominent, glomerular, subendothelial, immune-type electron deposits (original magnification × 11,400). Courtesy of John A. Minielly, MD.
Membranoproliferative glomerulonephritis (MPGN) type I. Glomerulus with mesangial interposition producing a double contouring of basement membranes, which, in areas, appear to surround subendothelial deposits (Jones silver methenamine–stained section; original magnification × 400). Courtesy of John A. Minielly, MD.
Membranoproliferative glomerulonephritis (MPGN) type II. Electron microscopy of glomerular basement membrane, intramembranous, somewhat linear, electron dense deposit (ie, dense deposit disease; original magnification × 11,400). Courtesy of John A. Minielly, MD.
Membranoproliferative glomerulonephritis (MPGN) type I. Immunofluorescent stained section. Intense, peripheral, glomerular, capillary loop deposition of immunoglobulin G (IgG) in an interrupted linear pattern corresponding to extensive subendothelial immune deposits (original magnification × 400). Courtesy of John A. Minielly, MD.

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Author

Pranay Kathuria, MD, FACP, FASN, FNKF Professor of Medicine, Director, Division of Nephrology and Hypertension, Program Director of Nephrology Fellowship, University of Oklahoma School of Community Medicine

Pranay Kathuria, MD, FACP, FASN, FNKF 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, National Kidney Foundation

Disclosure: Nothing to disclose.

Coauthor(s)

Akash Patel, MD Hospitalist, Tulsa Hospitalists, Inc

Akash Patel, MD is a member of the following medical societies: American College of Physicians, American Medical Student Association/Foundation

Disclosure: Nothing to disclose.

Specialty Editor Board

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

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ajay K Singh, MB, MRCP, MBA Associate Professor of Medicine, Harvard Medical School; Director of Dialysis, Renal Division, Brigham and Women's Hospital; Director, Brigham/Falkner Dialysis Unit, Faulkner Hospital

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FASN Professor of Medicine, Section of Nephrology-Hypertension, Deming Department of Medicine, Tulane University School of Medicine

Vecihi Batuman, MD, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

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, International Society of Nephrology

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Martin Senitko, MD, and Sandeep Singh, MD, to the development and writing of the source article.

Sections Membranoproliferative Glomerulonephritis
Overview
Presentation
DDx
Workup
Treatment
Medication
Media Gallery
References

Membranoproliferative Glomerulonephritis Differential Diagnoses

Diagnostic Considerations

Differential Diagnoses

References

Tables

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