title: Successful treatment of membranous glomerulonephritis with rituximab in calcineurin inhibitor-dependent patients.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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/m(2)). 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 CNIs and other immunosuppressant drugs could be withdrawn in all patients with no evidence of relapse.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.
authors.affiliation: Servicio de Nefrología Hospital Vall d'Hebrón, Barcelona, Spain. alsegarr@vhebron.net
authors.forename: Alfons
authors.initials: A
authors.lastname: Segarra
authors.forename: Manuel
authors.initials: M
authors.lastname: Praga
authors.forename: Natalia
authors.initials: N
authors.lastname: Ramos
authors.forename: Natalia
authors.initials: N
authors.lastname: Polanco
authors.forename: Isabel
authors.initials: I
authors.lastname: Cargol
authors.forename: Elena
authors.initials: E
authors.lastname: Gutierrez-Solis
authors.forename: M Rosa
authors.initials: MR
authors.lastname: Gomez
authors.forename: Bruno
authors.initials: B
authors.lastname: Montoro
authors.forename: Joaquim
authors.initials: J
authors.lastname: Camps
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D001706:Biopsy; D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D007668:Kidney / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D010865:Pilot Projects; D011507:Proteinuria / Q000188:drug therapy / Q000473:pathology; D012074:Remission Induction; D000069283:Rituximab; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000517:prevention & control
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D007155:Immunologic Factors; D000069283:Rituximab; D009173:Mycophenolic Acid