A new rescue regimen with plasma exchange and rituximab in high-risk membranous glomerulonephritis

Eur J Clin Invest. 2015 Dec;45(12):1260-9. doi: 10.1111/eci.12545. Epub 2015 Nov 9.

Abstract

Background: Even though current treatment guidelines for idiopathic membranous glomerulonephritis (iMGN) exist, many questions regarding an optimal therapy remain unanswered. Complete remission cannot be achieved in all patients; relapses occur, in some cases frequently, and side effects from the immunosuppressive therapy are common. Therapeutic options in high-risk patients not responding to standard immunosuppressive therapies are limited. Recent research reveals that the human M-type phospholipase A2 receptor (PLA2 R) is a causative factor in iMGN that parallels clinical disease activity. However, in some patients, this correlation is not evident and additional undetermined factors seem to play a role.

Design: We evaluated a new rescue protocol including plasma exchanges (PE) against albumin, intravenous immunoglobulins (IVIGs) and rituximab for 10 patients with a biopsy-proven diagnosis of iMGN who were therapy-resistant to all conventional regimens and had a urinary protein to creatinine ratio of more than 10 000 mg/g Crea. We compared this protocol with standard immunosuppressive protocols including monthly alternating prednisolone plus cyclophosphamide (18 patients), cyclosporine plus prednisolone (23 patients) and rituximab alone (eight patients) in a retrospective design.

Results: Our rescue regimen with PE, IVIGs and rituximab achieved partial remission in 90% of patients who had been otherwise refractory to therapy. The mean time to partial remission was 2·1 months. Furthermore, two anti-PLA2 R-antibody negative patients were also treated with this rescue regimen, achieving partial remission after 1 and 4 months.

Conclusion: A combination of PE, IVIGs and rituximab is a treatment option to consider for high-risk patients with iMGN who are refractory to conventional therapy.

Keywords: idiopathic membranous glomerulonephritis; maintenance therapy; partial remission; plasma exchange; rescue therapy; rituximab.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Cyclophosphamide / administration & dosage
  • Cyclosporine / administration & dosage
  • Drug Therapy, Combination
  • Female
  • Glomerulonephritis, Membranous / therapy*
  • Glucocorticoids / administration & dosage
  • Humans
  • Immunoglobulins, Intravenous / administration & dosage
  • Immunologic Factors / administration & dosage*
  • Immunosuppressive Agents / administration & dosage
  • Male
  • Methylprednisolone / administration & dosage
  • Middle Aged
  • Plasma Exchange / methods*
  • Prednisolone / administration & dosage
  • Recurrence
  • Remission Induction / methods
  • Retrospective Studies
  • Rituximab / administration & dosage*

Substances

  • Glucocorticoids
  • Immunoglobulins, Intravenous
  • Immunologic Factors
  • Immunosuppressive Agents
  • Rituximab
  • Cyclosporine
  • Cyclophosphamide
  • Prednisolone
  • Methylprednisolone