American Journal of Kidney Diseases
Volume 46, Issue 6 , Pages 1012-1029 , December 2005

Idiopathic Membranous Nephropathy: Outline and Rationale of a Treatment Strategy

Received 2 June 2005 ,Accepted 15 August 2005.

References 

  1. Haas M , Meehan SM , Karrison TG , Spargo BH . Changing etiologies of unexplained adult nephrotic syndrome (A comparison of renal biopsy findings from 1976-1979 and 1995-1997) . Am J Kidney Dis . 1997;30:621–631
  2. Schieppati A , Mosconi L , Perna A , et al.   Prognosis of untreated patients with idiopathic membranous nephropathy . N Engl J Med . 1993;329:85–89
  3. Ponticelli C , Zuchelli P , Passerini P , et al.   A 10-year follow-up of a randomized study with methylprednisolone and chlorambucil in membranous nephropathy . Kidney Int . 1995;48:1600–1604
  4. Cameron JS . Membranous nephropathy (The treatment dilemma) . Am J Kidney Dis . 1982;1:371–375
  5. Cameron JS . Membranous nephropathy—Still a treatment dilemma . N Engl J Med . 1992;327:638–639
  6. Glassock RJ . The treatment of idiopathic membranous nephropathy (A dilemma or a conundrum?) . Am J Kidney Dis . 2004;44:562–566
  7. Perna A , Schieppati A , Zamora J , Giuliano GA , Braun N , Remuzzi G . Immunosuppressive treatment for idiopathic membranous nephropathy (A systematic review) . Am J Kidney Dis . 2004;44:385–401
  8. du Buf-Vereijken PWG , Branten AJW , Wetzels JFM  Membranous Nephropathy Study Group . Cytotoxic therapy for membranous nephropathy and renal insufficiency; Improved renal survival but high relapse rate . Nephrol Dial Transplant . 2004;19:1142–1148
  9. Torres A , Dominguez-Gil B , Carreno A , et al.   Conservative versus immunosuppressive treatment of patients with idiopathic membranous nephropathy . Kidney Int . 2002;61:219–227
  10. Reichert LJM , Huysmans F ThM , Assmann K , Koene RAP , Wetzels JFM . Preserving renal function in patients with membranous nephropathy (Daily oral chlorambucil compared with intermittent monthly pulses of cyclophosphamide) . Ann Intern Med . 1994;121:328–333
  11. Reichert LJM , Koene RAP , Wetzels JFM . Urinary excretion of β2-microglobulin predicts renal outcome in patients with idiopathic membranous nephropathy . J Am Soc Nephrol . 1995;6:1666–1669
  12. Reichert LJM , Koene RAP , Wetzels JFM . Urinary IgG excretion as a prognostic factor in idiopathic membranous nephropathy . Clin Nephrol . 1997;48:79–84
  13. Wetzels JFM , Reichert LJM . Efficacy of immunosuppressive treatment in patients with membranous nephropathy and renal insufficiency . Kidney Int Suppl . 1997;61:S63–S66
  14. Branten AJW , Reichert LJM , Koene RAP , Wetzels JFM . Oral cyclophosphamide versus chlorambucil in the treatment of patients with idiopathic membranous nephropathy and renal insufficiency . Q J Med . 1998;91:359–366
  15. Branten AJW , Wetzels JFM . Short- and long-term efficacy of oral cyclophosphamide and steroids in patients with membranous nephropathy and renal insufficiency . Clin Nephrol . 2001;56:1–8
  16. du Buf-Vereijken PWG , Feith GW , Hollander D , et al.   Restrictive use of immunosuppressive treatment in patients with idiopathic membranous nephropathy (High renal survival in a large patient cohort) . Q J Med . 2004;97:353–360
  17. du Buf-Vereijken PWG , Wetzels JFM . Efficacy of a second course of immunosuppressive therapy in patients with membranous nephropathy and persistent or relapsing disease activity . Nephrol Dial Transplant . 2004;19:2036–2043
  18. Branten AJW , du Buf-Vereijken PWG , Klasen IS , et al.   Urinary excretion of β2-microglobulin and IgG predict prognosis in idiopathic membranous nephropathy (A validation study) . J Am Soc Nephrol . 2005;16:169–174
  19. Sarasin FP , Schifferli JA . Prophylactic oral anticoagulation in nephrotic patients with idiopathic membranous nephropathy . Kidney Int . 1994;45:578–585
  20. Erwin DT , Donadio JV , Holley KE . The clinical course of idiopathic membranous nephropathy . Mayo Clin Proc . 1973;48:697–712
  21. Ehrenreich T , Porush JG , Churg J , et al.   Treatment of idiopathic membranous nephropathy . N Engl J Med . 1976;295:741–746
  22. Bolton WK , Atuk N , Sturgill BC , Westervelt FB . Therapy of the idiopathic nephrotic syndrome with alternate day steroids . Am J Med . 1977;62:60–70
  23. Gluck MC , Gallo G , Lowenstein J , Baldwin DS . Membranous glomerulonephritis (Evolution of clinical and pathological features) . Ann Intern Med . 1973;16:13–19
  24. Pierides AM , Malasit P , Morley AR , Wilkinson R , Uldall PR , Kerr DNS . Idiopathic membranous nephropathy . Q J Med . 1977;182:163–177
  25. Franklin WA , Jennings RB , Earle DP . Membranous glomerulonephritis (Long-term serial observations on clinical course and morphology) . Kidney Int . 1973;4:36–56
  26. Row PG , Cameron JS , Turner DR , et al.   Membranous nephropathy; Long-term follow-up and association with neoplasia . Q J Med . 1975;174:207–239
  27. Forland M , Spargo BH . Clinicopathological correlation in idiopathic nephrotic syndrome with membranous nephropathy . Nephron . 1969;6:498–525
  28. Collaborative Study of the Adult Idiopathic Nephrotic Syndrome . A controlled study of short-term prednisone treatment in adults with membranous nephropathy . N Engl J Med . 1979;301:1301–1306
  29. Davison AM , Cameron JS , Kerr DN , Ogg CS , Wilkinson RW . The natural history of renal function in untreated idiopathic membranous glomerulonephritis in adults . Clin Nephrol . 1984;22:61–67
  30. MacTier R , Boulton Jones JM , Payton CD , McLay A . The natural history of membranous nephropathy in the west of Scotland . Q J Med . 1986;60:793–802
  31. Zuchelli P , Ponticelli C , Gagnoli P , Passerini P . Long-term outcome of idiopathic membranous nephropathy with nephrotic syndrome . Nephrol Dial Transplant . 1987;2:73–78
  32. Donadio JJV , Torres VE , Velosa JA , et al.   Idiopathic membranous nephropathy (The natural history of untreated patients) . Kidney Int . 1988;33:708–715
  33. Cattran DC , Delmore T , Roscoe J , et al.  Toronto Glomerulonephritis Study Group   A randomized controlled trial of prednisone in patients with idiopathic membranous nephropathy . N Engl J Med . 1989;320:210–215
  34. Wehrmann M , Bohle A , Bogenschutz O , et al.   Long-term prognosis of chronic idiopathic membranous glomerulonephritis. An analysis of 334 cases with particular regard to tubulo-interstitial changes . Clin Nephrol . 1989;31:67–76
  35. Cameron JS , Healy MJR , Adu D . The Medical Research Council trial of short-term high-dose alternate day prednisolone in idiopathic membranous nephropathy with nephrotic syndrome in adults . Q J Med . 1990;74:133–156
  36. Durin S , Barbanel C , Landais P , Noel LH , Grunfeld JP . Long term course of idiopathic extramembranous glomerulonephritis. Study of predictive factors of terminal renal insufficiency in 82 untreated patients . Nephrologie . 1990;11:67–71
  37. Noel LH , Zanetti M , Droz D . Long-term prognosis of idiopathic membranous glomerulonephritis . Am J Med . 1979;66:82–90
  38. Honkanen E , Tornroth T , Gronhagen-Riska C , Sankila R . Long-term survival in idiopathic membranous glomerulonephritis (Can the course be clinically predicted?) . Clin Nephrol . 1994;41:127–134
  39. Laluck BJ , Cattran DC . Prognosis after a complete remission in adult patients with idiopathic membranous nephropathy . Am J Kidney Dis . 1999;33:1026–1032
  40. Yoshimoto K , Yokoyama H , Wada T , et al.   Pathologic findings of initial biopsies reflect the outcomes of membranous nephropathy . Kidney Int . 2004;65:148–153
  41. Lewis EJ , Hunsicker LG , Bain RP , Rohde RD . The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group . N Engl J Med . 1993;329:1456–1462
  42. Brenner BM , Cooper ME , de Zeeuw D , et al.  RENAAL Study Investigators   Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy . N Engl J Med . 2001;345:861–869
  43. Jafar TH , Schmid CH , Landa M , et al.   Angiotension-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data . Ann Intern Med . 2001;135:73–87
  44. The Gisen Group . Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy . Lancet . 1997;349:1857–1863
  45. Stegeman CA , de Zeeuw D , de Jong PE . Treatment of idiopathic membranous nephropathy (The dilemma of who, when, and how) . Nephrol Dial Transplant . 1995;10:1982–1984
  46. Troyanov S , Wall CA , Miller JA , Scholey JW , Cattran DC  Toronto Glomerulonephritis Registry Group . Idiopathic membranous nephropathy (Definition and relevance of a partial remission) . Kidney Int . 2004;66:1199–1205
  47. Praga M , Borstein B , Andres A , et al.   Nephrotic proteinuria without hypoalbuminemia (Clinical characteristics and response to angiotensin-converting enzyme inhibition) . Am J Kidney Dis . 1991;17:330–338
  48. Praga M , Hernandez E , Montoyo C , Andres A , Ruilope LM , Rodicio JL . Long-term beneficial effects of angiotensin-converting enzyme inhibition in patients with nephrotic proteinuria . Am J Kidney Dis . 1992;20:240–248
  49. Ponticelli C , Passerini P , Altieri P , Locatelli F , Pappalettera M . Remissions and relapses in idiopathic membranous nephropathy . Nephrol Dial Transplant . 1992;7(suppl 1):S85–S90
  50. Reichert LJM , Koene RAP , Wetzels JFM . Prognostic factors in idiopathic membranous nephropathy . Am J Kidney Dis . 1998;31:1–11
  51. Passerini P , Pasquali P , Cesana B , Zucchelli P , Ponticelli C . Long-term outcome of patients with membranous nephropathy after complete remission of proteinuria . Nephrol Dial Transplant . 1989;4:525–529
  52. Rastogi SP , Hart-Mercer J , Kerr DN . Idiopathic membranous glomerulonephritis in adults (Remission following steroid therapy) . Q J Med . 1969;38:335–350
  53. Hopper J , Biava CG , Tu W-H . Membranous nephropathy (High dose alternate-day therapy with prednisone) . West J Med . 1981;135:1–8
  54. Short CD , Solomon LR , Gokal R , Mallick NP . Methylprednisolone in patients with membranous nephropathy and declining renal function . Q J Med . 1987;247:929–940
  55. Fuiano G , Stanziale P , Balletta M , et al.   Effectiveness of steroid therapy in different stages of membranous nephropathy . Nephrol Dial Transplant . 1989;4:1022–1029
  56. Brunkhorst R , Wrenger E , Koch KM . Low-dose prednisolone/chlorambucil therapy in patients with severe membranous glomerulonephritis . Clin Invest . 1994;72:277–282
  57. Bruns FJ , Adler S , Fraley DS , Segel DP . Sustained remission of membranous glomerulonephritis after cyclophosphamide and prednisone . Ann Intern Med . 1991;114:725–730
  58. Faedda R , Satta A , Bosincu L , Pirisi M , Bartoli E . Immune suppressive treatment of membranous glomerulonephritis . J Nephrol . 1995;8:107–112
  59. Falk RJ , Hogan SL , Muller KE , Jennette JC  Glomerular Disease Collaborative Network . Treatment of progressive membranous glomerulopathy . Ann Intern Med . 1992;116:438–445
  60. Jindal K , West M , Bear R , Goldstein M . Long-term benefits of therapy with cyclophosphamide and prednisone in patients with membranous glomerulonephritis and impaired renal function . Am J Kidney Dis . 1992;19:61–67
  61. Mathieson PW , Turner AN , Maidment CG , Evans DJ , Rees AJ . Prednisolone and chlorambucil treatment in idiopathic membranous nephropathy with deteriorating renal function . Lancet . 1988;2:869–872
  62. Ponticelli C , Zuchelli P , Passerini P , et al.   A randomized trial of methylprednisolone and chlorambucil in idiopathic membranous nephropathy . N Engl J Med . 1989;320:8–13
  63. Ponticelli C , Zuchelli P , Imbasciati E , et al.   Controlled trial of methylprednisolone and chlorambucil in idiopathic membranous nephropathy . N Engl J Med . 1984;310:946–950
  64. Warwick GL , Geddes CG , Boulton-Jones JM . Prednisolone and chlorambucil therapy for idiopathic membranous nephropathy with progressive renal failure . Q J Med . 1994;87:223–229
  65. Warwick GL , Boulton-Jones JM . Immunosuppression for membranous nephropathy . Lancet . 1988;1:1361; (letter)
  66. Murphy BF , McDonald I , Fairley KF , Kincaid-Smith PS . Randomized controlled trial of cyclophosphamide, warfarin and dipyridamole in idiopathic membranous glomerulonephritis . Clin Nephrol . 1992;37:229–234
  67. Donadio JJV , Holley KE , Anderson CF , Taylor WF . Controlled trial of cyclophosphamide in idiopathic membranous nephropathy . Kidney Int . 1974;6:431–439
  68. Braun N , Erley CM , Benda N , et al.   Therapy of membranous glomerulonephritis with nephrotic syndrome (5 Years follow-up of a prospective, randomized multi-center study) . J Am Soc Nephrol . 1995;6:413A; (abstr)
  69. Risler T , Braun N , Bach D , et al.   The German glomerulonephritis therapy study (10 Years of controlled randomized trials for the treatment of idiopathic glomerulonephritis) . Kidney Blood Press Res . 1996;19:196–200
  70. Wetzels JFM , Hoitsma AJ , Koene RAP . Immunosuppression for membranous nephropathy . Lancet . 1989;1:211; (letter)
  71. Branten AJW , Vervoort G , Wetzels JF . Serum creatinine is a poor marker of GFR in nephrotic syndrome . Nephrol Dial Transplant . 2005;20:707–711
  72. Ahuja M , Goumenos D , Shortland JR , Gerakis A , Brown CB . Does immunosuppression with prednisolone and azathioprine alter the progression of idiopathic membranous nephropathy? . Am J Kidney Dis . 1999;34:521–529
  73. Alexopoulos E , Sakellariou G , Memmos D , Karamitsos K , Leontsini M , Papadimitriou M . Cyclophosphamide provides no additional benefit to steroid therapy in the treatment of idiopathic membranous nephropathy . Am J Kidney Dis . 1993;21:497–503
  74. Bone JM , Rustom R , Williams PS . “Progressive” versus “indolent” idiopathic membranous glomerulonephritis . Q J Med . 1997;90:699–706
  75. Baker LRI , Tucker B , Macdougall IC . Treatment of idiopathic membranous nephropathy . Lancet . 1994;343:290–291 (letter)
  76. Brown JH , Alistair FD , Murphy BG , et al.   Treatment of renal failure in idiopathic membranous nephropathy with azathioprine and prednisolone . Nephrol Dial Transplant . 1998;13:443–448
  77. Cattran DC , Greenwood C , Ritchie S , et al.   A controlled trial of cyclosporine in patients with progressive membranous nephropathy . Kidney Int . 1995;47:1130–1135
  78. Cattran DC , Appel GB , Hebert LA , et al.   Cyclosporine in patients with steroid-resistant membranous nephropathy (A randomized trial) . Kidney Int . 2001;59:1484–1490
  79. Choi MJ , Eustace JA , Gimenez LF , et al.   Mycophenolate mofetil treatment for primary glomerular diseases . Kidney Int . 2002;61:1098–1114
  80. Guasch A , Suranyi M , Newton L , Hall BM , Myers BD . Short-term responsiveness of membranous glomerulopathy to cyclosporine . Am J Kidney Dis . 1992;20:472–481
  81. Miller G , Zimmerman R , Radhakrishnan J , Appel GB . Use of mycophenolate mofetil in resistant membranous nephropathy . Am J Kidney Dis . 2000;36:250–256
  82. Remuzzi G , Chiurchiu C , Abbate M , Brusegan V , Bontempelli M , Ruggenenti P . Rituximab for idiopathic membranous nephropathy . Lancet . 2002;360:923–924
  83. Rostoker G , Belghiti D , Maadi A-B , et al.   Long-term cyclosporin A therapy for severe idiopathic membranous nephropathy . Nephron . 1993;63:335–341
  84. Stirling CM , Simpson K , Boulton-Jones JM . Immunosuppression and outcome in idiopathic membranous nephropathy . Q J Med . 1998;9:159–164
  85. Western Canadian Glomerulonephritis Study Group . Controlled trial of azathioprine in the nephrotic syndrome secondary to idiopathic membranous glomerulonephritis . CMJ . 1976;115:1209–1210
  86. Williams PS , Bone JM . Immunosuppression can arrest progressive renal failure due to idiopathic membranous glomerulonephritis . Nephrol Dial Transplant . 1989;4:181–186
  87. Appel G , Nachman P , Hogan SL , et al.   Eculizumab (C5 complement inhibitor) in the treatment of idiopathic membranous nephropathy (Preliminary baseline and pharmacokinetic/pharmacodynamic data) . J Am Soc Nephrol . 2002;13:668A; (abstr)
  88. 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;56:1534–1543
  89. Picardi L , Villa G , Galli F , et al.   ACTH therapy in nephrotic syndrome induced by idiopathic membranous nephropathy . Clin Nephrol . 2004;62:403–404
  90. Ponticelli C , Altieri P , Scolari F , et al.   A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy . J Am Soc Nephrol . 1998;9:444–450
  91. Jayne D , Rasmussen N , Andrassy K , et al.   European Vasculitis Study Group (A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic antibodies) . N Engl J Med . 2003;349:36–44
  92. Wetzels JFM . Cyclophosphamide-induced gonadal toxicity (A treatment dilemma in patients with lupus nephritis?) . Neth J Med . 2004;62:347–352
  93. Zietse R , Wenting GJ , Kramer P , Mulder P , Schalekamp MA , Weimar W . Contrasting response to cyclosporin in refractory nephrotic syndrome . Clin Nephrol . 1989;31:22–25
  94. Schrijver G , Wetzels JFM , Robben JCM , Assmann KJM , Koene RAP , Berden JHM . Antiproteinuric effect of cyclosporin A in passive antiglomerular basement membrane nephritis in the mouse . Transplant Proc . 1988;20(suppl 4):S304–S308
  95. Schrijver G , Assmann KJM , Wetzels JFM , Berden JHM . Cyclosporin A reduces albuminuria in experimental anti-GBM glomerulonephritis independently from changes in GFR . Nephrol Dial Transplant . 1995;10:1149–1154
  96. Zietse R , Wenting GJ , Kramer P , Schalekamp MA , Weimar W . Effects of cyclosporine on glomerular barrier function in nephrotic syndrome . Clin Sci . 1992;82:641–650
  97. Ambalavanan S , Fauvel JP , Sibley RK , Myers BD . Mechanisms of the antiproteinuric effect of cyclosporine in membranous nephropathy . J Am Soc Nephrol . 1996;7:290–298
  98. Pisoni R , Grinyo JM , Salvadori M , et al.  The CYCLOMEN Study Group   Cyclosporine versus conservative therapy in patients with idiopathic membranous nephropathy and deteriorating renal function (Results of the CYCLOMEN trial) . J Am Soc Nephrol . 2000;11:0514A; (abstr)
  99. Ponticelli C , Villa M . Does cyclosporin have a role in the treatment of membranous nephropathy? . Nephrol Dial Transplant . 1999;14:23–25
  100. du Buf-Vereijken PW , Wetzels JFM . Mycophenolate mofetil versus cyclophosphamide in patients with idiopathic membranous nephropathy and renal insufficiency . J Am Soc Nephrol . 2004;15:341A; (abstr)
  101. Ruggenenti P , Chiurchiu C , Brusegan V , et al.   Rituximab in idiopathic membranous nephropathy (A one-year prospective study) . J Am Soc Nephrol . 2003;14:1851–1857
  102. Ruggenenti P , Chiurchiu C , Brusegan V , Perna A , Abbate M , Remuzzi G . Rituximab for idiopathic membranous nephropathy (Renal biopsy findings predict response to treatment) . J Am Soc Nephrol . 2003;14:528A; (abstr)
  103. Pei Y , Cattran DC , Greenwood C . Predicting chronic renal insufficiency in idiopathic membranous glomerulonephritis . Kidney Int . 1992;42:960–966
  104. Cattran DC , Pei Y , Greenwood CMT , Ponticelli C , Passerini P , Honkanen E . Validation of a predictive model of idiopathic membranous nephropathy (Its clinical and research implications) . Kidney Int . 1997;51:901–907
  105. Kon SP , Coupes B , Short CD , et al.   Urinary C5b-9 excretion and clinical course in idiopathic membranous nephropathy . Kidney Int . 1995;48:1953–1958
  106. Brenchley PE , Coupes B , Short CD , O’Donoghue DJ , Ballardie FW , Mallick NP . Urinary C3dg and C5b-9 indicate active immune disease in human membranous nephropathy . Kidney Int . 1992;41:933–937
  107. Bazzi C , Petrini C , Rizza V , et al.   Urinary excretion of IgG and α1-microglobulin predicts clinical course better than extent of proteinuria in membranous nephropathy . Am J Kidney Dis . 2001;38:240–248
  108. Bazzi C , D’Amico G . The urinary excretion of IgG and alpha1-microglobulin predicts renal outcome and identifies patients deserving treatment in membranous nephropathy . Kidney Int . 2002;61:2276
  109. Branten AJ , Kock-Jansen M , Klasen IS , Wetzels JF . Urinary excretion of complement C3d in patients with renal diseases . Eur J Clin Invest . 2003;33:449–456
  110. Cattran DC , Wald R , Brenchley PE , Coupes B . Clinical correlates of serial urinary membrane attack complex estimates in patients with idiopathic membranous nephropathy . Clin Nephrol . 2003;60:7–12

 Supported in part by grant no. NSN: PC152 from the Dutch Kidney Foundation (P.W.G.d.B.-V.) and grant no. NWO-MW 920-03-038 from the Dutch Science Foundation (A.J.W.B.).Originally published online as doi:10.1053/j.ajkd.2005.08.020 on October 13, 2005.

PII: S0272-6386(05)01238-2

doi: 10.1053/j.ajkd.2005.08.020

American Journal of Kidney Diseases
Volume 46, Issue 6 , Pages 1012-1029 , December 2005

Article Tools

* Image Usage & Resolution