title: Anti-CD25 monoclonal antibody replacement therapy for chronic kidney disease in liver transplant recipients.
abstract: BACKGROUND
  Chronic kidney disease (CKD) is a frequent complication after liver transplantation (LT) and is associated with increased mortality. Strategies to reduce calcineurin inhibitor (CNI) dose or conversion to either mycophenolate mofetil and/or rapamycin resulted in variable results and side-effect profiles.
  
  
  METHODS
  We evaluated the effectiveness of CNI conversion to long-term anti-CD25 monoclonal antibody (mAb)-based immunosuppression in 15 adult LT patients with CKD at 7.6±4 years posttransplant (intervention group). Three patients had been previously switched to rapamycin, and 12 patients were on CNI. The control group included 15 LT patients on CNI with stable renal function over a similar posttransplant follow-up period.
  
  
  RESULTS
  Anti-CD25 mAb were given over a period of 26±15 months (range, 2-51 months) and were well tolerated. The slope of calculated creatinine clearance was -0.66 mL/min/month over 6 months before conversion and -0.05 mL/min/month after conversion to anti-CD25 mAb (P=0.16 and P=0.86 vs. controls). Three acute rejection episodes occurred in the intervention group. Acute rejection was reversible in two patients. However, one patient died of chronic rejection 1 year after having been switched to tacrolimus. Anti-CD25 mAb were replaced with either CNI or rapamycin in six patients (acute rejection [n=2], progression to end-stage renal disease [n=2], poor venous status [n=1], increased liver enzymes [n=1]).
  
  
  CONCLUSIONS
  The use of long-term anti-CD25 mAb therapy as a replacement to CNI and rapamycin-based immunosuppression may be feasible. It is crucial that rejection surveillance is intensified. A randomized controlled trial is required to confirm the benefits of this strategy.
authors.affiliation: Department of Medicine, McGill University Health Center, Montreal, Quebec, Canada.
authors.forename: Chris
authors.initials: C
authors.lastname: Walsh
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Barkun
authors.forename: Jean
authors.initials: J
authors.lastname: Tchervenkov
authors.forename: Marc
authors.initials: M
authors.lastname: Deschenes
authors.forename: Peter
authors.initials: P
authors.lastname: Ghali
authors.forename: Philip
authors.initials: P
authors.lastname: Wong
authors.forename: Prosanto
authors.initials: P
authors.lastname: Chaudhury
authors.forename: Steven
authors.initials: S
authors.lastname: Paraskevas
authors.forename: Peter
authors.initials: P
authors.lastname: Metrakos
authors.forename: Marcelo
authors.initials: M
authors.lastname: Cantarovich
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D065095:Calcineurin Inhibitors; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000209:etiology; D012189:Retrospective Studies; D020123:Sirolimus / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use; D014180:Transplantation; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D020123:Sirolimus; D016559:Tacrolimus