American Journal of Kidney Diseases
Volume 45, Issue 4 , Pages 788-789, April 2005

Cyclophosphamide or chlorambucil therapy is indicated in idiopathic membranous nephropathy with strong risk factors for progression

Ohio State University Medical Center, Columbus, Ohio

published online 01 March 2005.

Article Outline

 

To the Editor:

The systematic review by Perna et al of idiopathic membranous nephropathy (IMN) therapy1 is timely and rigorous but leaves the reader with a crucial unresolved paradox: alkylating agent therapy (chlorambucil or cyclophosphamide [CML/CTX]) significantly increased complete remission rate (CML/CTX versus placebo, P = 0.004; CML/CTX versus steroids, P = 0.0003) but did not decrease end-stage renal disease (ESRD) rate. The paradox is that IMN complete remission should prevent ESRD.2

Glassock’s editorial3 identifies Perna’s paradox and provides plausible explanations. However, its clinical significance is not discussed. We suggest the following:

•CML/CTX therapy induces complete IMN remission better than other therapies.1

•Complete IMN remission prevents progression to ESRD2 and other risks of prolonged nephrotic syndrome, especially atherosclerosis and thrombosis.4

•Appropriate CML/CTX therapy (Ponticelli et al5 or comparable protocol4) is well tolerated.

•Thus, CML/CTX therapy is justified in IMN if 1 or more strong progression risk factors are present (nephrotic-range proteinuria despite ≥6 months of aggressive antiproteinuria therapy,6 elevated serum creatinine, and kidney biopsy evidence of chronicity).4, 7

With this strategy we have only rarely observed IMN progression to ESRD. Between 1983 and 1999 only 2 of our 134 IMN patients progressed to ESRD despite CML/CTX therapy.

We suggest that CML/CTX is the gold standard to which other IMN therapies should be compared. Until better data become available, no IMN nephrotic patient with strong progression risk factors should be denied CML/CTX therapy, especially if cyclosporin,8 mycophenolate,9 or rituximab10 therapy was unsuccessful.

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References 

  1. 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
  2. Troyanov S , Wall CA , Miller JA , Scholey JW , Cattran DC . Idiopathic membranous nephropathy (Definition and relevance of a partial remission) . Kidney Int . 2004;66:1199–1205
  3. Glassock RJ . The treatment of idiopathic membranous nephropathy (A dilemma or a conundrum?) . Am J Kidney Dis . 2004;44:562–566
  4. Hebert L . Glomerular Diseases (The American College of Physicians Nephrology Medical Knowledge Self Assessment Program (MKSAP)) . Philadelphia, PA: American College of Physicians-American Society of Internal Medicine; 1998;
  5. Ponticelli C , Zucchelli 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
  6. Wilmer WA , Rovin BH , Hebert CJ , Rao SV , Kumor K , Hebert LA . Management of glomerular proteinuria (A commentary) . J Am Soc Nephrol . 2003;14:3217–3232
  7. Cattran DC , Pei Y , Greenwood CM , 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
  8. 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
  9. Spetie DN , Tang Y , Rovin BH , et al.   Mycophenolate therapy of SLE membranous nephropathy . Kidney Int . 2004;66:2411–2415
  10. Remuzzi G , Chiurchiu C , Abbate M , Brusegan V , Bontempelli M , Ruggenenti P . Rituximab for idiopathic membranous nephropathy . Lancet . 2002;360:923–924

 Originally published online as doi:10.1053/j.ajkd.2005.01.033 on February 28, 2005.

PII: S0272-6386(05)00133-2

doi:10.1053/j.ajkd.2005.01.033

Refers to article:

  • Immunosuppressive treatment for idiopathic membranous nephropathy: A systematic review

    Annalisa Perna, Arrigo Schieppati, Javier Zamora, Giovanni A. Giuliano, Norbert Braun, Giuseppe Remuzzi
    American Journal of Kidney Diseases September 2004 (Vol. 44, Issue 3, Pages 385-401)

American Journal of Kidney Diseases
Volume 45, Issue 4 , Pages 788-789, April 2005

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