Skip to main content

Advertisement

SpringerLink
Log in

Treatment of primary membranous nephropathy: where are we now?

Journal of Nephrology Aims and scope Submit manuscript

Abstract

In the last 10 years, basic science and clinical research have made important contributions to the understanding and management of primary membranous nephropathy (MN). The identification of antibodies directed against the M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A protein have added a new perspective on diagnosis, monitoring the immunological activity, predicting prognosis and guiding therapy in patients with primary MN. Mounting evidence suggests that quantification and follow-up of antiPLA2R Abs levels can help in assessing prognosis and evaluate the response to treatment. The kidney disease improving global outcomes guidelines published in 2012 have not been updated. New data on the use of rituximab suggest it should be considered as a potential initial therapy in the treatment of patients with primary MN.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price includes VAT (France)

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Gesualdo L, Di Palma AM, Morrone LF, Strippoli GF, Schena FP, Italian Immunopathology Group ISoN (2004) The Italian experience of the national registry of renal biopsies. Kidney Int 66(3):890–894

    Article  PubMed  Google Scholar 

  2. Heymann W, Hackel DB, Harwood S, Wilson SG, Hunter JL (1959) Production of nephrotic syndrome in rats by Freund’s adjuvants and rat kidney suspensions. Proc Soc Exp Biol Med 100(4):660–664

    Article  PubMed  CAS  Google Scholar 

  3. Debiec H, Guigonis V, Mougenot B, Haymann JP, Bensman A, Deschenes G, Ronco PM (2003) Antenatal membranous glomerulonephritis with vascular injury induced by anti-neutral endopeptidase antibodies: toward new concepts in the pathogenesis of glomerular diseases. J Am Soc Nephrol 14(Suppl 1):S27–S32

    Article  PubMed  Google Scholar 

  4. Beck LH Jr, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, Klein JB, Salant DJ (2009) M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med 361(1):11–21

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Tomas NM, Beck LH Jr, Meyer-Schwesinger C, Seitz-Polski B, Ma H, Zahner G, Dolla G, Hoxha E, Helmchen U, Dabert-Gay AS et al (2014) Thrombospondin type-1 domain-containing 7 A in idiopathic membranous nephropathy. N Engl J Med 371(24):2277–2287

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Hofstra JM, Fervenza FC, Wetzels JF (2013) Treatment of idiopathic membranous nephropathy. Nat Rev Nephrol 9(8):443–458

    Article  PubMed  CAS  Google Scholar 

  7. Ramachandran R, Kumar V, Kumar A, Yadav AK, Nada R, Kumar H, Kumar V, Rathi M, Kohli HS, Gupta KL et al (2016) PLA2R antibodies, glomerular PLA2R deposits and variations in PLA2R1 and HLA-DQA1 genes in primary membranous nephropathy in South Asians. Nephrol Dial Transplant 31(9):1486–1493

    Article  PubMed  CAS  Google Scholar 

  8. De Vriese AS, Glassock RJ, Nath KA, Sethi S, Fervenza FC (2017) A proposal for a serology-based approach to membranous nephropathy. J Am Soc Nephrol 28(2):421–430

    Article  PubMed  Google Scholar 

  9. Ronco P, Debiec H (2015) Pathophysiological advances in membranous nephropathy: time for a shift in patient’s care. Lancet 385(9981):1983–1992

    Article  PubMed  Google Scholar 

  10. Du Y, Li J, He F, Lv Y, Liu W, Wu P, Huang J, Wei S, Gao H (2014) The diagnosis accuracy of PLA2R-AB in the diagnosis of idiopathic membranous nephropathy: a meta-analysis. PLoS One 9(8):e104936

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Pani A, Porta C, Cosmai L, Melis P, Floris M, Piras D, Gallieni M, Rosner M, Ponticelli C (2016) Glomerular diseases and cancer: evaluation of underlying malignancy. J Nephrol 29(2):143–152

    Article  PubMed  Google Scholar 

  12. Timmermans SA, Ayalon R, van Paassen P, Beck LH Jr, van Rie H, Wirtz JJ, Verseput GH, Frenken LA, Salant DJ, Cohen Tervaert JW et al (2013) Anti-phospholipase A2 receptor antibodies and malignancy in membranous nephropathy. Am J Kidney Dis 62(6):1223–1225

    Article  PubMed  CAS  Google Scholar 

  13. Qin W, Beck LH Jr, Zeng C, Chen Z, Li S, Zuo K, Salant DJ, Liu Z (2011) Anti-phospholipase A2 receptor antibody in membranous nephropathy. J Am Soc Nephrol 22(6):1137–1143

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Xie Q, Li Y, Xue J, Xiong Z, Wang L, Sun Z, Ren Y, Zhu X, Hao CM (2015) Renal phospholipase A2 receptor in hepatitis B virus-associated membranous nephropathy. Am J Nephrol 41(4–5):345–353

    Article  PubMed  CAS  Google Scholar 

  15. Larsen CP, Messias NC, Silva FG, Messias E, Walker PD (2013) Determination of primary versus secondary membranous glomerulopathy utilizing phospholipase A2 receptor staining in renal biopsies. Mod Pathol 26(5):709–715

    Article  PubMed  CAS  Google Scholar 

  16. Stehle T, Audard V, Ronco P, Debiec H (2015) Phospholipase A2 receptor and sarcoidosis-associated membranous nephropathy. Nephrol Dial Transplant 30(6):1047–1050

    Article  PubMed  CAS  Google Scholar 

  17. Hoxha E, Wiech T, Stahl PR, Zahner G, Tomas NM, Meyer-Schwesinger C, Wenzel U, Janneck M, Steinmetz OM, Panzer U et al (2016) A mechanism for cancer-associated membranous nephropathy. N Engl J Med 374(20):1995–1996

    Article  PubMed  CAS  Google Scholar 

  18. Hoxha E, Beck LH Jr, Wiech T, Tomas NM, Probst C, Mindorf S, Meyer-Schwesinger C, Zahner G, Stahl PR, Schopper R et al (2017) An indirect immunofluorescence method facilitates detection of thrombospondin type 1 domain-containing 7 A-specific antibodies in membranous nephropathy. J Am Soc Nephrol 28(2):520–531

    Article  PubMed  CAS  Google Scholar 

  19. Murtas C, Ghiggeri GM (2016) Membranous glomerulonephritis: histological and serological features to differentiate cancer-related and non-related forms. J Nephrol 29(4):469–478

    Article  PubMed  CAS  Google Scholar 

  20. Polanco N, Gutierrez E, Covarsi A, Ariza F, Carreno A, Vigil A, Baltar J, Fernandez-Fresnedo G, Martin C, Pons S et al (2010) Spontaneous remission of nephrotic syndrome in idiopathic membranous nephropathy. J Am Soc Nephrol 21(4):697–704

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Pei Y, Cattran D, Greenwood C (1992) Predicting chronic renal insufficiency in idiopathic membranous glomerulonephritis. Kidney Int 42(4):960–966

    Article  PubMed  CAS  Google Scholar 

  22. Cattran DC, Pei Y, Greenwood CM, Ponticelli C, Passerini P, Honkanen E (1997) Validation of a predictive model of idiopathic membranous nephropathy: its clinical and research implications. Kidney Int 51(3):901–907

    Article  PubMed  CAS  Google Scholar 

  23. van den Brand JA, Hofstra JM, Wetzels JF (2012) Prognostic value of risk score and urinary markers in idiopathic membranous nephropathy. Clin J Am Soc Nephrol 7(8):1242–1248

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Hofstra JM, Beck LH Jr, Beck DM, Wetzels JF, Salant DJ (2011) Anti-phospholipase A(2) receptor antibodies correlate with clinical status in idiopathic membranous nephropathy. Clin J Am Soc Nephrol 6(6):1286–1291

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Hoxha E, Harendza S, Pinnschmidt HO, Tomas NM, Helmchen U, Panzer U, Stahl RA (2015) Spontaneous remission of proteinuria is a frequent event in phospholipase A2 receptor antibody-negative patients with membranous nephropathy. Nephrol Dial Transplant 30(11):1862–1869

    Article  PubMed  CAS  Google Scholar 

  26. Hoxha E, Harendza S, Pinnschmidt H, Panzer U, Stahl RA (2014) PLA2R antibody levels and clinical outcome in patients with membranous nephropathy and non-nephrotic range proteinuria under treatment with inhibitors of the renin-angiotensin system. PLoS One 9(10):e110681

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Bech AP, Hofstra JM, Brenchley PE, Wetzels JF (2014) Association of anti-PLA(2)R antibodies with outcomes after immunosuppressive therapy in idiopathic membranous nephropathy. Clin J Am Soc Nephrol 9(8):1386–1392

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Kanigicherla D, Gummadova J, McKenzie EA, Roberts SA, Harris S, Nikam M, Poulton K, McWilliam L, Short CD, Venning M et al (2013) Anti-PLA2R antibodies measured by ELISA predict long-term outcome in a prevalent population of patients with idiopathic membranous nephropathy. Kidney Int 83(5):940–948

    Article  PubMed  CAS  Google Scholar 

  29. Hofstra JM, Debiec H, Short CD, Pelle T, Kleta R, Mathieson PW, Ronco P, Brenchley PE, Wetzels JF (2012) Antiphospholipase A2 receptor antibody titer and subclass in idiopathic membranous nephropathy. J Am Soc Nephrol 23(10):1735–1743

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Hoxha E, Harendza S, Pinnschmidt H, Panzer U, Stahl RA (2014) M-type phospholipase A2 receptor autoantibodies and renal function in patients with primary membranous nephropathy. Clin J Am Soc Nephrol 9(11):1883–1890

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Ruggenenti P, Debiec H, Ruggiero B, Chianca A, Pelle T, Gaspari F, Suardi F, Gagliardini E, Orisio S, Benigni A et al (2015) Anti-phospholipase A2 receptor antibody titer predicts post-rituximab outcome of membranous nephropathy. J Am Soc Nephrol 26(10):2545–2558

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Kidney Disease (2012) Improving global outcomes (KDIGO) glomerulonephritis work group. KDIGO clinical practice guideline for glomerulonephritis. Kidney Int Suppl(2):186–197

    Google Scholar 

  33. du Buf-Vereijken PW, Branten AJ, Wetzels JF (2005) Idiopathic membranous nephropathy: outline and rationale of a treatment strategy. Am J Kidney Dis 46(6):1012–1029

    Article  PubMed  CAS  Google Scholar 

  34. Lionaki S, Derebail VK, Hogan SL, Barbour S, Lee T, Hladunewich M, Greenwald A, Hu Y, Jennette CE, Jennette JC et al (2012) Venous thromboembolism in patients with membranous nephropathy. Clin J Am Soc Nephrol 7(1):43–51

    Article  PubMed  CAS  Google Scholar 

  35. A controlled study of short-term prednisone treatment in adults with membranous nephropathy (1979) Collaborative Study of the adult idiopathic nephrotic syndrome. N Engl J Med 301(24):1301–1306

    Article  Google Scholar 

  36. Cattran DC, Delmore T, Roscoe J, Cole E, Cardella C, Charron R, Ritchie S (1989) A randomized controlled trial of prednisone in patients with idiopathic membranous nephropathy. N Engl J Med 320(4):210–215

    Article  PubMed  CAS  Google Scholar 

  37. Cameron JS, Healy MJ, Adu D (1990) The medical research council trial of short-term high-dose alternate day prednisolone in idiopathic membranous nephropathy with nephrotic syndrome in adults. The MRC Glomerulonephritis Working Party. Q J Med 74(274):133–156

    Article  PubMed  CAS  Google Scholar 

  38. Chen Y, Schieppati A, Chen X, Cai G, Zamora J, Giuliano GA, Braun N, Perna A (2014) Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndrome. Cochrane Database Syst Rev 2014(10):CD004293

    Google Scholar 

  39. Hogan SL, Muller KE, Jennette JC, Falk RJ (1995) A review of therapeutic studies of idiopathic membranous glomerulopathy. Am J Kidney Dis 25(6):862–875

    Article  PubMed  CAS  Google Scholar 

  40. Imperiale TF, Goldfarb S, Berns JS (1995) Are cytotoxic agents beneficial in idiopathic membranous nephropathy? A meta-analysis of the controlled trials. J Am Soc Nephrol 5(8):1553–1558

    PubMed  CAS  Google Scholar 

  41. Ponticelli C, Zucchelli P, Imbasciati E, Cagnoli L, Pozzi C, Passerini P, Grassi C, Limido D, Pasquali S, Volpini T et al (1984) Controlled trial of methylprednisolone and chlorambucil in idiopathic membranous nephropathy. N Engl J Med 310(15):946–950

    Article  PubMed  CAS  Google Scholar 

  42. Ponticelli C, Zucchelli P, Passerini P, Cesana B, Locatelli F, Pasquali S, Sasdelli M, Redaelli B, Grassi C, Pozzi C et al (1995) A 10-year follow-up of a randomized study with methylprednisolone and chlorambucil in membranous nephropathy. Kidney Int 48(5):1600–1604

    Article  PubMed  CAS  Google Scholar 

  43. Ponticelli C, Altieri P, Scolari F, Passerini P, Roccatello D, Cesana B, Melis P, Valzorio B, Sasdelli M, Pasquali S et al (1998) A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy. J Am Soc Nephrol 9(3):444–450

    PubMed  CAS  Google Scholar 

  44. Jha V, Ganguli A, Saha TK, Kohli HS, Sud K, Gupta KL, Joshi K, Sakhuja V (2007) A randomized, controlled trial of steroids and cyclophosphamide in adults with nephrotic syndrome caused by idiopathic membranous nephropathy. J Am Soc Nephrol 18(6):1899–1904

    Article  PubMed  CAS  Google Scholar 

  45. Howman A, Chapman TL, Langdon MM, Ferguson C, Adu D, Feehally J, Gaskin GJ, Jayne DR, O’Donoghue D, Boulton-Jones M et al (2013) Immunosuppression for progressive membranous nephropathy: a UK randomised controlled trial. Lancet 381(9868):744–751

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Pani A (2013) Standard immunosuppressive therapy of immune-mediated glomerular diseases. Autoimmun Rev 12(8):848–853

    Article  PubMed  CAS  Google Scholar 

  47. Torres A, Dominguez-Gil B, Carreno A, Hernandez E, Morales E, Segura J, Gonzalez E, Praga M (2002) Conservative versus immunosuppressive treatment of patients with idiopathic membranous nephropathy. Kidney Int 61(1):219–227

    Article  PubMed  CAS  Google Scholar 

  48. Cattran DC, Greenwood C, Ritchie S, Bernstein K, Churchill DN, Clark WF, Morrin PA, Lavoie S (1995) A controlled trial of cyclosporine in patients with progressive membranous nephropathy. Canadian Glomerulonephritis Study Group. Kidney Int 47(4):1130–1135

    Article  PubMed  CAS  Google Scholar 

  49. Cattran DC, Appel GB, Hebert LA, Hunsicker LG, Pohl MA, Hoy WE, Maxwell DR, Kunis CL, North America Nephrotic Syndrome Study G (2001) Cyclosporine in patients with steroid-resistant membranous nephropathy: a randomized trial. Kidney Int 59(4):1484–1490

    Article  PubMed  CAS  Google Scholar 

  50. Praga M, Barrio V, Juarez GF, Luno J (2007) Grupo Espanol de Estudio de la Nefropatia M: Tacrolimus monotherapy in membranous nephropathy: a randomized controlled trial. Kidney Int 71(9):924–930

    Article  PubMed  CAS  Google Scholar 

  51. Caro J, Gutierrez-Solis E, Rojas-Rivera J, Agraz I, Ramos N, Rabasco C, Espinosa M, Valera A, Martin M, Frutos MA et al (2015) Predictors of response and relapse in patients with idiopathic membranous nephropathy treated with tacrolimus. Nephrol Dial Transplant 30(3):467–474

    Article  PubMed  CAS  Google Scholar 

  52. Alexopoulos E, Papagianni A, Tsamelashvili M, Leontsini M, Memmos D (2006) Induction and long-term treatment with cyclosporine in membranous nephropathy with the nephrotic syndrome. Nephrol Dial Transplant 21(11):3127–3132

    Article  PubMed  CAS  Google Scholar 

  53. Miller G, Zimmerman R 3rd, Radhakrishnan J, Appel G (2000) Use of mycophenolate mofetil in resistant membranous nephropathy. Am J Kidney Dis 36(2):250–256

    Article  PubMed  CAS  Google Scholar 

  54. Dussol B, Morange S, Burtey S, Indreies M, Cassuto E, Mourad G, Villar E, Pouteil-Noble C, Karaaslan H, Sichez H et al (2008) Mycophenolate mofetil monotherapy in membranous nephropathy: a 1-year randomized controlled trial. Am J Kidney Dis 52(4):699–705

    Article  PubMed  CAS  Google Scholar 

  55. Branten AJ, du Buf-Vereijken PW, Vervloet M, Wetzels JF (2007) Mycophenolate mofetil in idiopathic membranous nephropathy: a clinical trial with comparison to a historic control group treated with cyclophosphamide. Am J Kidney Dis 50(2):248–256

    Article  PubMed  CAS  Google Scholar 

  56. Baker LR, Tucker B, Macdougall IC, Oommen R (1997) Treatment of progressive renal failure and nephrotic syndrome with azathioprine and prednisolone. Postgrad Med J 73(864):647–648

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Goumenos DS, Ahuja M, Davlouros P, El Nahas AM, Brown CB (2006) Prednisolone and azathioprine in membranous nephropathy: a 10-year follow-up study. Clin Nephrol 65(5):317–323

    Article  PubMed  CAS  Google Scholar 

  58. Kattah AG, Fervenza FC (2012) Rituximab: emerging treatment strategies of immune-mediated glomerular disease. Expert Rev Clin Immunol 8(5):413–421

    Article  PubMed  CAS  Google Scholar 

  59. Remuzzi G, Chiurchiu C, Abbate M, Brusegan V, Bontempelli M, Ruggenenti P (2002) Rituximab for idiopathic membranous nephropathy. Lancet 360(9337):923–924

    Article  PubMed  CAS  Google Scholar 

  60. Ruggenenti P, Chiurchiu C, Brusegan V, Abbate M, Perna A, Filippi C, Remuzzi G (2003) Rituximab in idiopathic membranous nephropathy: a one-year prospective study. J Am Soc Nephrol 14(7):1851–1857

    Article  PubMed  CAS  Google Scholar 

  61. Fervenza FC, Cosio FG, Erickson SB, Specks U, Herzenberg AM, Dillon JJ, Leung N, Cohen IM, Wochos DN, Bergstralh E et al (2008) Rituximab treatment of idiopathic membranous nephropathy. Kidney Int 73(1):117–125

    Article  PubMed  CAS  Google Scholar 

  62. Fervenza FC, Abraham RS, Erickson SB, Irazabal MV, Eirin A, Specks U, Nachman PH, Bergstralh EJ, Leung N, Cosio FG et al (2010) Rituximab therapy in idiopathic membranous nephropathy: a 2-year study. Clin J Am Soc Nephrol 5(12):2188–2198

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Ruggenenti P, Cravedi P, Chianca A, Perna A, Ruggiero B, Gaspari F, Rambaldi A, Marasa M, Remuzzi G (2012) Rituximab in idiopathic membranous nephropathy. J Am Soc Nephrol 23(8):1416–1425

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Busch M, Ruster C, Schinkothe C, Gerth J, Wolf G (2013) Rituximab for the second- and third-line therapy of idiopathic membranous nephropathy: a prospective single center study using a new treatment strategy. Clin Nephrol 80(2):105–113

    Article  PubMed  CAS  Google Scholar 

  65. Dahan K, Debiec H, Plaisier E, Cachanado M, Rousseau A, Wakselman L, Michel PA, Mihout F, Dussol B, Matignon M et al (2017) Rituximab for severe membranous nephropathy: a 6-month trial with extended follow-up. J Am Soc Nephrol 28(1):348–358

    Article  PubMed  CAS  Google Scholar 

  66. US Food and Drug Administration. Drug safety communications. https://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm126519.htm. Accessed 2 June 2017

  67. Calabrese LH, Molloy ES, Huang D, Ransohoff RM (2007) Progressive multifocal leukoencephalopathy in rheumatic diseases: evolving clinical and pathologic patterns of disease. Arthritis Rheum 56(7):2116–2128

    Article  PubMed  Google Scholar 

  68. Kusumoto S, Tanaka Y, Ueda R, Mizokami M (2011) Reactivation of hepatitis B virus following rituximab-plus-steroid combination chemotherapy. J Gastroenterol 46(1):9–16

    Article  PubMed  CAS  Google Scholar 

  69. Reddy KR, Beavers KL, Hammond SP, Lim JK, Falck-Ytter YT, American Gastroenterological Association (2015) I: American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology 148(1):215–219 (quiz e216–217)

    Article  PubMed  CAS  Google Scholar 

  70. Cho SF, Wu WH, Yang YH, Chang CS (2015) Risk of second primary cancer in patients with B-cell non-Hodgkin lymphoma receiving rituximab-containing chemotherapy: a nationwide population-based study. Anticancer Res 35(3):1809–1814

    PubMed  CAS  Google Scholar 

  71. Fleury I, Chevret S, Pfreundschuh M, Salles G, Coiffier B, van Oers MH, Gisselbrecht C, Zucca E, Herold M, Ghielmini M et al (2016) Rituximab and risk of second primary malignancies in patients with non-Hodgkin lymphoma: a systematic review and meta-analysis. Ann Oncol 27(3):390–397

    Article  PubMed  CAS  Google Scholar 

  72. Tarella C, Passera R, Magni M, Benedetti F, Rossi A, Gueli A, Patti C, Parvis G, Ciceri F, Gallamini A et al (2011) Risk factors for the development of secondary malignancy after high-dose chemotherapy and autograft, with or without rituximab: a 20-year retrospective follow-up study in patients with lymphoma. J Clin Oncol 29(7):814–824

    Article  PubMed  CAS  Google Scholar 

  73. Cravedi P, Ruggenenti P, Sghirlanzoni MC, Remuzzi G (2007) Titrating rituximab to circulating B cells to optimize lymphocytolytic therapy in idiopathic membranous nephropathy. Clin J Am Soc Nephrol 2(5):932–937

    Article  PubMed  CAS  Google Scholar 

  74. Ruggenenti P, Fervenza FC, Remuzzi G (2017) Treatment of membranous nephropathy: time for a paradigm shift. Nat Rev Nephrol 13(9):563–579

  75. Benucci M, Saviola G, Baiardi P, Manfredi M (2011) Cost-effectiveness treatment with Rituximab in patients with rheumatoid arthritis in real life. Rheumatol Int 31(11):1465–1469

    Article  PubMed  CAS  Google Scholar 

  76. Porter D, van Melckebeke J, Dale J, Messow CM, McConnachie A, Walker A, Munro R, McLaren J, McRorie E, Packham J et al (2016) Tumour necrosis factor inhibition versus rituximab for patients with rheumatoid arthritis who require biological treatment (ORBIT): an open-label, randomised controlled, non-inferiority, trial. Lancet 388(10041):239–247

    Article  PubMed  CAS  Google Scholar 

  77. Danese MD, Reyes CM, Gleeson ML, Halperin M, Skettino SL, Mikhael J (2016) Estimating the population benefits and costs of rituximab therapy in the United States from 1998 to 2013 using real-world data. Med Care 54(4):343–349

    Article  PubMed  PubMed Central  Google Scholar 

  78. Granata F, Petraroli A, Boilard E, Bezzine S, Bollinger J, Del Vecchio L, Gelb MH, Lambeau G, Marone G, Triggiani M (2005) Activation of cytokine production by secreted phospholipase A2 in human lung macrophages expressing the M-type receptor. J Immunol 174(1):464–474

    Article  PubMed  CAS  Google Scholar 

  79. Rojas-Rivera J, Fernandez-Juarez G, Ortiz A, Hofstra J, Gesualdo L, Tesar V, Wetzels J, Segarra A, Egido J, Praga M (2015) A European multicentre and open-label controlled randomized trial to evaluate the efficacy of Sequential treatment with TAcrolimus-Rituximab versus steroids plus cyclophosphamide in patients with primary MEmbranous Nephropathy: the STARMEN study. Clin Kidney J 8(5):503–510

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Gong R (2011) The renaissance of corticotropin therapy in proteinuric nephropathies. Nat Rev Nephrol 8(2):122–128

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Lindskog A, Ebefors K, Johansson ME, Stefansson B, Granqvist A, Arnadottir M, Berg AL, Nystrom J, Haraldsson B (2010) Melanocortin 1 receptor agonists reduce proteinuria. J Am Soc Nephrol 21(8):1290–1298

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Berg AL, Nilsson-Ehle P, Arnadottir M (1999) Beneficial effects of ACTH on the serum lipoprotein profile and glomerular function in patients with membranous nephropathy. Kidney Int 56(4):1534–1543

    Article  PubMed  CAS  Google Scholar 

  83. Ponticelli C, Passerini P, Salvadori M, Manno C, Viola BF, Pasquali S, Mandolfo S, Messa P (2006) A randomized pilot trial comparing methylprednisolone plus a cytotoxic agent versus synthetic adrenocorticotropic hormone in idiopathic membranous nephropathy. Am J Kidney Dis 47(2):233–240

    Article  PubMed  CAS  Google Scholar 

  84. Bomback AS, Canetta PA, Beck LH Jr, Ayalon R, Radhakrishnan J, Appel GB (2012) Treatment of resistant glomerular diseases with adrenocorticotropic hormone gel: a prospective trial. Am J Nephrol 36(1):58–67

    Article  PubMed  CAS  Google Scholar 

  85. Hladunewich MA, Cattran D, Beck LH, Odutayo A, Sethi S, Ayalon R, Leung N, Reich H, Fervenza FC (2014) A pilot study to determine the dose and effectiveness of adrenocorticotrophic hormone (H.P. Acthar(R) Gel) in nephrotic syndrome due to idiopathic membranous nephropathy. Nephrol Dial Transplant 29(8):1570–1577

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Jain P, O’Brien S (2013) Anti-CD20 monoclonal antibodies in chronic lymphocytic leukemia. Expert Opin Biol Ther 13(2):169–182

    Article  PubMed  CAS  Google Scholar 

  87. Cang S, Mukhi N, Wang K, Liu D (2012) Novel CD20 monoclonal antibodies for lymphoma therapy. J Hematol Oncol 5:64

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Hahn BH (2013) Belimumab for systemic lupus erythematosus. N Engl J Med 368(16):1528–1535

    Article  PubMed  CAS  Google Scholar 

  89. Willcocks L, Barrett C, Brenchley P, Schmidt T, Gisbert S, Cai G, Savage C, Jones R (2015) Effect of belimumab on proteinuria and anti-Pla2r autoantibody in idiopathic membranous nephropathy-6 months data. Nephrol Dial Transpl 30(3):iii32–iii33

  90. Hartono C, Chung M, Kuo SF, Seshan SV, Muthukumar T (2014) Bortezomib therapy for nephrotic syndrome due to idiopathic membranous nephropathy. J Nephrol 27(1):103–106

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Barbari A, Chehadi R, Kfoury Assouf H, Kamel G, Jaafar M, Abdallah A, Rizk S, Masri M (2017) Bortezomib as a novel approach to early recurrent membranous glomerulonephritis after kidney transplant refractory to combined conventional rituximab therapy. Exp Clin Transplant 15(3):350–354

    PubMed  Google Scholar 

  92. van de Donk NW, Janmaat ML, Mutis T, Lammerts van Bueren JJ, Ahmadi T, Sasser AK, Lokhorst HM, Parren PW (2016) Monoclonal antibodies targeting CD38 in hematological malignancies and beyond. Immunol Rev 270(1):95–112

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgements

The authors declare that they do not have any conflict of interest that positively or negatively influenced the article’s content.

Funding

We did not receive any funding to support this review.

Author information

Author notes

    Authors and Affiliations

    1. Division of Nephrology and Dialysis, Azienda Ospedaliera G. Brotzu, Piazzale Ricchi n 1, 09100, Cagliari, Italy

      Andrea Angioi, Nicola Lepori & Antonello Pani

    2. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, USA

      Ana Coloma López & Fernando C. Fervenza

    3. Department of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA

      Sanjeev Sethi

    Authors
    1. Andrea Angioi
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Nicola Lepori
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Ana Coloma López
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Sanjeev Sethi
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Fernando C. Fervenza
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Antonello Pani
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Antonello Pani.

    Ethics declarations

    Conflict of interest

    The authors declare that they have no competing interests.

    Ethical approval

    This research does not involve human subjects and human data, but only reports clinical trials and observational studies published in the literature in peer reviewed journals.

    Additional information

    Andrea Angioi, Nicola Lepori, and Ana Coloma López contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Angioi, A., Lepori, N., López, A.C. et al. Treatment of primary membranous nephropathy: where are we now?. J Nephrol 31, 489–502 (2018). https://doi.org/10.1007/s40620-017-0427-5

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s40620-017-0427-5

    Keywords

    Search

    Navigation