title: Membranous nephropathy: Pilot study of a novel regimen combining cyclosporine and Rituximab.
abstract: BACKGROUND
  There is broad consensus that high grade basal proteinuria and failure to achieve remission of proteinuria are key determinants of adverse renal prognosis in patients with primary membranous nephropathy. Based on the fact that current regimens are not ideal due to short and long-term toxicity and propensity to relapse after treatment withdrawal, we developed a treatment protocol based on a novel combination of rituximab and cyclosporine which targets both the B and T cell limbs of the immune system. Herein, we report pilot study data on proteinuria, changes in autoantibody levels and renal function that offer a potentially effective new approach to treatment of severe membranous nephropathy.
  
  
  METHODS
  Thirteen high-risk patients defined by sustained high-grade proteinuria (mean 10.8 g/d) received combination induction therapy with rituximab plus cyclosporine for 6 months, followed by a second cycle of rituximab and tapering of cyclosporine during an 18 month maintenance phase.
  
  
  RESULTS
  Mean proteinuria decreased by 65% at 3 months and by 80% at 6 months. Combined complete or partial remission was achieved in 92% of patients by 9 months; 54% achieved complete remission at 12 months. Two patients relapsed during the trial. All patients with autoantibodies to PLA2R achieved antibody depletion. Renal function stabilized. The regimen was well tolerated.
  
  
  CONCLUSIONS
  We report these encouraging preliminary results for their potential value to other investigators needing prospectively collected data to inform the design and power calculations of future randomized clinical trials. Such trials will be needed to formally compare this novel regimen to current therapies for membranous nephropathy.
authors.affiliation: Kidney Disease Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD (NIH).
authors.forename: Meryl
authors.initials: M
authors.lastname: Waldman
authors.affiliation: Department of Medicine, Section of Nephrology, Boston University School of Medicine, Boston, MA.
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Beck
authors.affiliation: Kidney Disease Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD (NIH).
authors.forename: Michelle
authors.initials: M
authors.lastname: Braun
authors.affiliation: Biostatistics Program, Office of Director, NIDDK NIH.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Wilkins
authors.affiliation: Kidney Disease Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD (NIH).
authors.forename: James E
authors.initials: JE
authors.lastname: Balow
authors.affiliation: Kidney Disease Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD (NIH).
authors.forename: Howard A
authors.initials: HA
authors.lastname: Austin
keywords: Membranous nephropathy; cyclosporine; nephrotic syndrome; rituximab