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Published ahead of print on May 28, 2009
Clin J Am Soc Nephrol 4: 1083-1088, 2009
© 2009 American Society of Nephrology
doi: 10.2215/CJN.06041108

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Clinical Nephrology

Successful Treatment of Membranous Glomerulonephritis with Rituximab in Calcineurin Inhibitor-Dependent Patients

Alfons Segarra*, Manuel Praga{dagger}, Natalia Ramos*, Natalia Polanco{dagger}, Isabel Cargol{ddagger}, Elena Gutierrez-Solis{dagger}, M. Rosa Gomez§, Bruno Montoro§, and Joaquim Camps*

* Servicio de Nefrología Hospital Vall d'Hebrón, Barcelona, Spain; {dagger} Servicio de Nefrologia, Hospital 12 de Octubre, Madrid, Spain; and {ddagger} Servicio de Bioquimica and § Servicio de Farmacia Hospitalaria, Hospital Vall d'Hebrón, Barcelona, Spain

Correspondence: Dr. Alfons Segarra, Servicio de Nefrologia, Anexo planta 7, Hospital Valle Hebrón, Paseo Valle Hebrón 119-129, Barcelona 08035, Spain. Phone: 93 274 61 52; Fax: 93 274 62 04; E-mail: alsegarr{at}vhebron.net

Background and objectives: Calcineurin inhibitors (CNIs) induce remission of proteinuria in most nephrotic patients with membranous glomerulonephropathy (MGN). However, 60% of patients become treatment dependent and are at risk of chronic nephrotoxicity. The aim of this study was to evaluate the efficacy of rituximab in patients with long-term dependence on CNIs.

Design, setting, participants, and measurements: Thirteen patients with MGN, normal renal function, and proven dependence on CNIs, despite previous treatment with other immunosuppressant drugs, received a single trial of four weekly doses of rituximab (375 mg/m2). Outcome measures were the percentage of patients with CNI withdrawal and no evidence of relapse and the percentage of patients with complete or partial remission 30 mo after CNI withdrawal.

Results: After rituximab, proteinuria decreased significantly (2.5 ± 0,76 basal versus 0.85 ± 0.17 at 6 mo; P = .0003). CNIs and other immunosuppressant drugs could be withdrawn in all patients with no evidence of relapse. After CNI withdrawal, GFR increased significantly (90.3 ± 15 basal to 106.4 ± 20 at 3 mo with a mean increase of 15.3% [range 0–20]). Three patients suffered a relapse of nephrotic proteinuria 19, 23, and 28 mo after rituximab treatment; all were successfully treated with a second course of rituximab. At 30 mo, all patients were in remission.

Conclusions: In patients with MGN with long-term CNI dependence, rituximab can be an effective tool to overcome dependence on CNI, thus avoiding the risk of nephrotoxicity related to the chronic exposure to these drugs.


Related Article

Overcoming Calcineurin Dependence in Membranous Nephropathy: Is Rituximab the Answer?
Fernando C. Fervenza
Clin. J. Am. Soc. Nephrol. 2009 4: 1017-1019. [Full Text] [PDF]



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F. C. Fervenza
Overcoming Calcineurin Dependence in Membranous Nephropathy: Is Rituximab the Answer?
Clin. J. Am. Soc. Nephrol., June 1, 2009; 4(6): 1017 - 1019.
[Full Text] [PDF]




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