title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. georg.boehmig@meduniwien.ac.at
authors.forename: Christoph
authors.initials: C
authors.lastname: Schwarz
authors.forename: Heinz
authors.initials: H
authors.lastname: Regele
authors.forename: Nicole
authors.initials: N
authors.lastname: Huttary
authors.forename: Markus
authors.initials: M
authors.lastname: Wahrmann
authors.forename: Markus
authors.initials: M
authors.lastname: Exner
authors.forename: Katalyn
authors.initials: K
authors.lastname: Nagy-Bojarsky
authors.forename: Josef
authors.initials: J
authors.lastname: Kletzmayr
authors.forename: Walter H
authors.initials: WH
authors.lastname: Hörl
authors.forename: Georg A
authors.initials: GA
authors.lastname: Böhmig
mesh_terms: D000328:Adult; D000368:Aged; D015704:CD4 Antigens / Q000032:analysis; D002908:Chronic Disease; D004338:Drug Combinations; D005260:Female; D006084:Graft Rejection / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007674:Kidney Diseases / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D020127:Recovery of Function / Q000187:drug effects; D012720:Severity of Illness Index; D016559:Tacrolimus / Q000008:administration & dosage; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D015704:CD4 Antigens; D004338:Drug Combinations; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus