title: Rituximab therapy in idiopathic membranous nephropathy: a 2-year study.
abstract: OBJECTIVE
  It was postulated that in patients with membranous nephropathy (MN), four weekly doses of Rituximab (RTX) would result in more effective B cell depletion, a higher remission rate, and maintaining the same safety profile compared with patients treated with RTX dosed at 1 g every 2 weeks. This hypothesis was supported by previous pharmacokinetic (PK) analysis showing that RTX levels in the two-dose regimen were 50% lower compared with nonproteinuric patients, which could potentially result in undertreatment.
  
  
  METHODS
  Twenty patients with MN and proteinuria >5 g/24 h received RTX (375 mg/m(2) × 4), with re-treatment at 6 months regardless of proteinuria response. PK analysis was conducted simultaneously with immunological analyses of T and B cells to ascertain the effect of RTX on lymphocyte subpopulations.
  
  
  RESULTS
  Baseline proteinuria of 11.9 g/24 h decreased to 4.2 and 2.0 g/24 h at 12 and 24 months, respectively, whereas creatinine clearance increased from 72.4 ml/min per 1.73 m(2) at baseline to 88.4 ml/min per 1.73 m(2) at 24 months. Of 18 patients who completed 24-month follow-up, 4 are in complete remission, 12 are in partial remission, 1 has a limited response, and 1 patient relapsed. Serum RTX levels were similar to those obtained with two doses of RTX.
  
  
  CONCLUSIONS
  Four doses of RTX resulted in more effective B cell depletion, but proteinuria reduction was similar to RTX at 1 g every 2 weeks. Baseline quantification of lymphocyte subpopulations did not predict response to RTX therapy.
authors: Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, MN 55901, USA. fervenza.fernando@mayo.edu
authors: Fernando C
authors: FC
authors: Fervenza
authors: Roshini S
authors: RS
authors: Abraham
authors: Stephen B
authors: SB
authors: Erickson
authors: Maria Valentina
authors: MV
authors: Irazabal
authors: Alfonso
authors: A
authors: Eirin
authors: Ulrich
authors: U
authors: Specks
authors: Patrick H
authors: PH
authors: Nachman
authors: Eric J
authors: EJ
authors: Bergstralh
authors: Nelson
authors: N
authors: Leung
authors: Fernando G
authors: FG
authors: Cosio
authors: Marie C
authors: MC
authors: Hogan
authors: John J
authors: JJ
authors: Dillon
authors: LaTonya J
authors: LJ
authors: Hickson
authors: Xujian
authors: X
authors: Li
authors: Daniel C
authors: DC
authors: Cattran
mesh_terms: D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018941:Antigens, CD19 / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology; D016516:CD4-CD8 Ratio; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000069283:Rituximab