Highlights & Basics
- Membranous nephropathy is a chronic, immunologically mediated disease of the glomerular basement membrane that may resolve spontaneously, persist with stable renal function, or progress to kidney failure. It is one of the most common causes of nephrotic syndrome in adults.
- A diagnosis of primary membranous nephropathy should only be made after secondary causes have been excluded. Definitive diagnosis is based on renal biopsy findings.
- Approach to treatment is guided by risk (low, moderate, high, or very high) of progressive kidney injury.
- Treatment in low-risk patients is largely conservative, including a low-sodium and low-protein diet and statins for hyperlipidemia. Hypertension is treated with ACE inhibitors or angiotensin II receptor antagonists, and edema can be managed with the use of diuretics.
- Moderate, high, and very high-risk patients may be treated with a combination of corticosteroids with either cytotoxic alkylating agents, cyclosporine, or rituximab.
Quick Reference
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Citations
Couser WG. Primary Membranous Nephropathy. Clin J Am Soc Nephrol. 2017 Jun 7;12(6):983-997.[Abstract][Full Text]
Ronco P, Beck L, Debiec H, et al. Membranous nephropathy. Nat Rev Dis Primers. 2021 Sep 30;7(1):69.[Abstract][Full Text]
Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Kidney Int. 2021 Oct;100(4s):S1-S276.[Abstract][Full Text]
Peterson JC, Adler S, Burkart JM, et al. Blood pressure control, proteinuria, and the progression of renal disease. The modification of diet in renal disease study. Ann Intern Med. 1995 Nov 15;123(10):754-62.[Abstract]
von Groote TC, Williams G, Au EH, et al. Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome. Cochrane Database Syst Rev. 2021 Nov 15;11(11):CD004293.[Abstract][Full Text]
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3. Haas M, Meehan SM, Karrison TG, et al. Changing etiologies of unexplained adult nephrotic syndrome: a comparison of renal biopsy findings from 1976-1979 and 1995-1997. Am J Kidney Dis. 1997 Nov;30(5):621-31.[Abstract]
4. Ronco P, Beck L, Debiec H, et al. Membranous nephropathy. Nat Rev Dis Primers. 2021 Sep 30;7(1):69.[Abstract][Full Text]
5. Heymann W, Hackel DB, Harwood S, et al. Production of nephrotic syndrome in rats by Freund's adjuvants and rat kidney suspension. Proc Soc Exp Biol Med. 1959;100:660-4.
6. Debiec H, Guigonis V, Mougenot B, et al. Antenatal membranous glomerulonephritis due to anti-neutral endopeptidase antibodies. N Engl J Med. 2002 Jun 27;346(26):2053-60.[Abstract][Full Text]
7. Ronco P, Debiec H. Molecular pathomechanisms of membranous nephropathy: from Heymann nephritis to alloimmunization. J Am Soc Nephrol. 2005 May;16(5):1205-13.[Abstract]
8. Beck LH Jr, Bonegio RG, Lambeau G, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009;361:11-21.[Abstract][Full Text]
9. Qin W, Beck LH Jr, Zeng C, et al. Anti-phospholipase A2 receptor antibody in membranous nephropathy. J Am Soc Nephrol. 2011 Jun;22(6):1137-43.[Abstract]
10. Iwakura T, Ohashi N, Kato A, et al. Prevalence of enhanced granular expression of thrombospondin type-1 domain-containing 7A in the glomeruli of Japanese patients with idiopathic membranous nephropathy. PLoS One. 2015;10:e0138841.[Abstract][Full Text]
11. Reichert LJ, Koene RA, Wetzels JF. Prognostic factors in idiopathic membranous nephropathy. Am J Kidney Dis. 1998;31:1-11.[Abstract]
12. Mok CC. Membranous nephropathy in systemic lupus erythematosus: a therapeutic enigma. Nat Rev Nephrol. 2009 Apr;5(4):212-20.[Abstract]
13. Johnson RJ, Couser WG. Hepatitis B infection and renal disease: clinical, immunopathogenetic and therapeutic considerations. Kidney Int. 1990 Feb;37(2):663-76.[Abstract]
14. Johnson RJ, Gretch DR, Yamabe H, et al. Membranoproliferative glomerulonephritis associated with hepatitis C virus infection. N Engl J Med. 1993 Feb 18;328(7):465-70.[Abstract][Full Text]
15. Ronco PM. Paraneoplastic glomerulopathies: new insights into an old entity. Kidney Int. 1999 Jul;56(1):355-77.[Abstract][Full Text]
16. Hogan JJ, Markowitz GS, Radhakrishnan J. Drug-induced glomerular disease: immune-mediated injury. Clin J Am Soc Nephrol. 2015 Jul 7;10(7):1300-10.[Abstract][Full Text]
17. Stehlé T, Joly D, Vanhille P, et al. Clinicopathological study of glomerular diseases associated with sarcoidosis: a multicenter study. Orphanet J Rare Dis. 2013 Apr 30;8:65.[Abstract][Full Text]
18. Ivanyi B. A primer on recurrent and de novo glomerulonephritis in renal allografts. Nat Clin Pract Nephrol. 2008 Aug;4(8):446-57.[Abstract][Full Text]
19. Tomas NM, Beck LH Jr, Meyer-Schwesinger C, et al. Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med. 2014 Dec 11;371(24):2277-87.[Abstract][Full Text]
20. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Kidney Int. 2021 Oct;100(4s):S1-S276.[Abstract][Full Text]
21. Ehrenreich T, Churg J. Pathology of membranous nephropathy. Pathol Annu. 1968;3:145-86.
22. Kidney Disease: Improving Global Outcomes. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Jan 2013 [internet publication].[Full Text]
23. Jefferson JA, Couser WG. Therapy of membranous nephropathy associated with malignancy and secondary causes. Semin Nephrol. 2003 Jul;23(4):400-5.[Abstract][Full Text]
24. Giordano M, De Feo P, Lucidi P, et al. Effects of dietary protein restriction on fibrinogen and albumin metabolism in nephrotic patients. Kidney Int. 2001 Jul;60(1):235-42.[Abstract][Full Text]
25. Peterson JC, Adler S, Burkart JM, et al. Blood pressure control, proteinuria, and the progression of renal disease. The modification of diet in renal disease study. Ann Intern Med. 1995 Nov 15;123(10):754-62.[Abstract]
26. von Groote TC, Williams G, Au EH, et al. Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome. Cochrane Database Syst Rev. 2021 Nov 15;11(11):CD004293.[Abstract][Full Text]
27. Lu W, Gong S, Li J, et al. Efficacy and safety of rituximab in the treatment of membranous nephropathy: a systematic review and meta-analysis. Medicine (Baltimore). 2020 Apr;99(16):e19804.[Abstract][Full Text]
28. Dussol B, Morange S, Burtey S, et al. Mycophenolate mofetil monotherapy in membranous nephropathy: a 1-year randomized controlled trial. Am J Kidney Dis. 2008 Oct;52(4):699-705.[Abstract]
29. Nikolopoulou A, Condon M, Turner-Stokes T, et al. Mycophenolate mofetil and tacrolimus versus tacrolimus alone for the treatment of idiopathic membranous glomerulonephritis: a randomised controlled trial. BMC Nephrol. 2019 Sep 6;20(1):352.[Abstract][Full Text]
30. Chan TM, Lin AW, Tang SC, et al. Prospective controlled study on mycophenolate mofetil and prednisolone in the treatment of membranous nephropathy with nephrotic syndrome. Nephrology (Carlton). 2007 Dec;12(6):576-81.[Abstract]
31. Branten AJ, du Buf-Vereijken PW, Vervloet M, et al. Mycophenolate mofetil in idiopathic membranous nephropathy: a clinical trial with comparison to a historic control group treated with cyclophosphamide. Am J Kidney Dis. 2007 Aug;50(2):248-56.[Abstract]
32. Scolari F, Alberici F, Mescia F, et al. Therapies for membranous nephropathy: a tale from the old and new millennia. Front Immunol. 2022;13:789713.[Abstract][Full Text]
33. Berg AL, Arnadottir M. ACTH-induced improvement in the nephrotic syndrome in patients with a variety of diagnoses. Nephrol Dial Transplant. 2004;19:1305-7.[Full Text]
34. Berg AL, Nilsson-Ehle P, Arnadottir M. Beneficial effects of ACTH on the serum lipoprotein profile and glomerular function in patients with membranous nephropathy. Kidney Int. 1999 Oct;56(4):1534-43.[Abstract][Full Text]
35. ClinicalTrials.gov. Adrenocorticotropic hormone in membranous nephropathy. ClinicalTrials.gov identifier: NCT03025828. Aug 2022. [internet publication].[Full Text]
36. Ponticelli C, Passerini P, Salvadori M, et al. A randomized pilot trial comparing methylprednisolone plus a cytotoxic agent versus synthetic adrenocorticotropic hormone in idiopathic membranous nephropathy. Am J Kidney Dis. 2006 Feb;47(2):233-40.[Abstract]
