title: Independent of nephrectomy, weaning immunosuppression leads to late sensitization after kidney transplant failure.
abstract: BACKGROUND
  Patients returning to dialysis therapy after renal transplant failure have a high rate of human leukocyte antigen antibody sensitization, and sensitization has been linked to allograft nephrectomy. We hypothesized that nephrectomy for cause is a consequence of weaning immunosuppression and that weaning leads to sensitization even in the absence of nephrectomy.
  
  
  METHODS
  We examined outcomes in 300 consecutive patients with kidney allograft failure and survival of more than 30 days after failure. We analyzed a subset of 119 patients with a low panel reactive antibody (PRA) before transplantation and follow-up PRA testing at 6 to 24 months after failure (late PRA).
  
  
  RESULTS
  By late PRA testing, 56% of patients were highly sensitized (class I or II PRA ≥80%). On multivariate analysis controlling for human leukocyte antigen matching, allograft nephrectomy, and other variables, weaning of immunosuppression predicted high sensitization (odds ratio, 14.34; P=0.004). In a subset of patients, the percentage of those who were highly sensitized increased from 21% at the time of failure on immunosuppressive therapy to 68% by late PRA after weaning (P<0.001). Conversely, patients who maintained immunosuppression showed minimal sensitization after failure. Transplant nephrectomy was required in 41% of patients who weaned immunosuppression versus 0% of the 24 patients who maintained immunosuppression with calcineurin inhibitor therapy after failure (P<0.001).
  
  
  CONCLUSIONS
  Weaning immunosuppression was a triggering event leading to late rejection and allograft nephrectomy and was an independent predictor of alloantibody sensitization after kidney allograft failure.
authors.affiliation: Department of Medicine, University Hospitals Case Medical Center, Cleveland, OH 44106, USA. joshua.augustine@uhhospitals.org
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Augustine
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Woodside
authors.forename: Aparna
authors.initials: A
authors.lastname: Padiyar
authors.forename: Edmund Q
authors.initials: EQ
authors.lastname: Sanchez
authors.forename: Donald E
authors.initials: DE
authors.lastname: Hricik
authors.forename: James A
authors.initials: JA
authors.lastname: Schulak
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D016009:Chi-Square Distribution; D004334:Drug Administration Schedule; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009392:Nephrectomy / Q000009:adverse effects*; D016017:Odds Ratio; D009820:Ohio; D006435:Renal Dialysis; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D001323:Autoantibodies; D006680:HLA Antigens; D007166:Immunosuppressive Agents