Bortezomib as a Novel Approach to Early Recurrent Membranous Glomerulonephritis After Kidney Transplant Refractory to Combined Conventional Rituximab Therapy

Exp Clin Transplant. 2017 Jun;15(3):350-354. doi: 10.6002/ect.2016.0350. Epub 2017 Apr 3.

Abstract

We report a case of early recurrent membranous glomerulonephritis after kidney transplant from a deceased donor. The patient received induction therapy and was discharged with a serum creatinine level of 0.78 mg/dL on triple maintenance immunosuppressive therapy, which included tacrolimus, mycophenolate mofetil, and prednisone. At 7 months after transplant, a graft biopsy for new-onset isolated proteinuria (2.7 g/day) revealed stage 2 recurrent membranous glomerulonephritis. In the face of persistent proteinuria despite combined conservative rituximab therapy over several months and the total eradication of CD20-positive cells, bortezomib was introduced. This resulted in a substantial decline in proteinuria within 2 months and its subsequent disappearance several months later. This was paralleled by a considerable drop in plasma CD34-positive and CD138-positive cell counts. These preliminary observations indicate that recurrent posttransplant membranous glomerulonephritis is associated in part with a B-cell- mediated immunologic process that may involve both CD20-positive and plasma cells. Rituximab-resistant or partially responsive recurrent posttransplant membranous glomerulonephritis may benefit from a proteasome inhibitor-based therapy.

Publication types

  • Case Reports

MeSH terms

  • Biopsy
  • Bortezomib / therapeutic use*
  • Drug Resistance*
  • Drug Substitution
  • Drug Therapy, Combination
  • Fluorescent Antibody Technique
  • Glomerulonephritis, Membranous / diagnosis
  • Glomerulonephritis, Membranous / drug therapy*
  • Glomerulonephritis, Membranous / immunology
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Kidney / drug effects*
  • Kidney / immunology
  • Kidney / ultrastructure
  • Kidney Failure, Chronic / diagnosis
  • Kidney Failure, Chronic / immunology
  • Kidney Failure, Chronic / surgery*
  • Kidney Transplantation / adverse effects*
  • Male
  • Microscopy, Electron
  • Middle Aged
  • Recurrence
  • Remission Induction
  • Rituximab / adverse effects
  • Rituximab / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Rituximab
  • Bortezomib