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

Abstract

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.

• Authors: Christoph Schwarz, Heinz Regele, Nicole Huttary, Markus Wahrmann, Markus Exner, Katalyn Nagy-Bojarsky, Josef Kletzmayr, Walter H Hörl, Georg A Böhmig
• Journal: Wiener klinische Wochenschrift (Wien Klin Wochenschr) Vol. 118 Issue 13-14 Pg. 397-404 (Jul 2006) ISSN: 0043-5325 [Print] Austria
• PMID: 16865644 (Publication Type: Clinical Trial, Journal Article)

Chemical References

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

Topics

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