Rescue therapy with tacrolimus and mycophenolate mofetil does not prevent deterioration of graft function in C4d-positive chronic allograft nephropathy

Wien Klin Wochenschr. 2006 Jul;118(13-14):397-404. doi: 10.1007/s00508-006-0531-3.


Background: Humoral alloresponses may contribute to chronic allograft nephropathy (CAN) in a subset of kidney transplant recipients. For chronic humoral rejection, the efficacy of rescue therapy with tacrolimus and mycophenolate mofetil has been suggested.

Methods: Eleven recipients with C4d-positive CAN (index biopsy performed after a median of 3 years posttransplantation), who had been on cyclosporine A-based immunosuppression, were converted to tacrolimus, and if not part of basal therapy, to mycophenolate mofetil. We evaluated the effect of this tacrolimus/mycophenolate mofetil rescue therapy on clinical outcomes and on alloantibody formation detected with flow cytometric testing of panel-reactive antibody.

Results: Tacrolimus/mycophenolate mofetil rescue therapy (plus anti-rejection treatment in six recipients with additional signs of acute cellular rejection) failed to prevent progressive deterioration of graft function. Four patients returned to dialysis after 4 to 18 months. Serial post-transplant serology detected HLA class I and/or II reactivity in seven recipients. Tacrolimus/mycophenolate mofetil therapy did not affect the time course of alloantibody levels. One patient with C4d-positive transplant glomerulopathy, who did not respond to tacrolimus/mycophenolate mofetil rescue therapy, developed nephrotic-range proteinuria associated with a rapid decline of allograft function. Despite considerable reduction in alloantibody levels and nearly complete clearance of C4d deposits, immunoadsorption failed to prevent graft failure in this patient.

Conclusion: Our data argue against the efficacy of tacrolimus/mycophenolate mofetil rescue therapy in established C4d-positive chronic allograft dysfunction. Prospective trials are needed to evaluate whether early initiation of this or other antihumoral strategies are capable of effectively preventing alloantibody-mediated chronic graft injury.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • CD4 Antigens / analysis
  • Chronic Disease
  • Drug Combinations
  • Female
  • Graft Rejection / etiology*
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects*
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Kidney Diseases / etiology*
  • Kidney Diseases / immunology
  • Kidney Diseases / prevention & control*
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / immunology
  • Male
  • Middle Aged
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / analogs & derivatives*
  • Recovery of Function / drug effects
  • Severity of Illness Index
  • Tacrolimus / administration & dosage
  • Transplantation, Homologous / adverse effects
  • Transplantation, Homologous / immunology
  • Treatment Outcome


  • CD4 Antigens
  • Drug Combinations
  • Immunosuppressive Agents
  • Mycophenolic Acid
  • Tacrolimus