title: Preformed donor-specific antibodies and risk of antibody-mediated rejection in repeat renal transplantation.
abstract: BACKGROUND
  Allograft outcomes in patients undergoing repeat renal transplantation are inferior compared to first-time transplant recipient outcomes. Donor-specific antibodies detected by solid-phase assays (DSA-SPA) may contribute to the worse prognosis. The influence of DSA-SPA on repeat renal transplantation outcomes has not been previously studied in detail.
  
  
  METHODS
  This study reports the findings in 174 patients who underwent repeat renal transplantation between years 2007 and 2012. These included 62 patients with preformed DSA-SPA detected by Luminex at the time of transplantation. Patients received standard and consistent immunosuppression and were monitored closely for evidence of rejection. Recipients who underwent desensitization were excluded from this analysis. Endpoints included development of biopsy-proven acute rejection and analysis of graft survival and function.
  
  
  RESULTS
  Patients in the DSA-SPA-positive and DSA-SPA-negative groups received similar immunosuppression, and a similar proportion of recipients had a peak panel reactive antibody greater than 20%; the two groups differed with respect to human leukocyte antigen mismatches (4.7 ± 1.1 vs. 4.1 ± 1.7, P=0.024). Recipients with preformed DSA-SPA had higher rejection rates (54.8% vs. 34.8%, P=0.01), including higher rates of antibody-mediated rejection (AMR) (32.3% vs. 7.1%, P<0.001). Recipients who were DSA-SPA-positive and flow cytometry crossmatch (FCXM)-positive had a higher incidence of both AMR (OR 4.6, P=0.009) and of acute rejection (OR 3.57, P=0.02) as compared to those who were DSA-SPA-positive and FCXM-negative. Overall allograft survival was similar in the DSA-SPA-positive and DSA-SPA-negative groups (log-rank test=0.63, P=0.428). Differences in allograft function were detectable after 2 years (32.8 ± 13.1 vs. 47 ± 20.2 mL/min/1.73 m(2), P=0.023) and may be reflective of more AMR among DSA-SPA-positive patients.
  
  
  CONCLUSIONS
  This analysis suggests that DSA-SPA increases the overall risk of acute rejection but does not appear to adversely impact allograft survival during the early follow-up period. Close monitoring of renal function and early biopsy for AMR detection appear to allow for satisfactory short-term allograft outcomes in repeat transplant recipients.
authors.affiliation: 1 Department of Pharmacy, NewYork-Presbyterian Hospital, Columbia University Medical Center, New York, NY. 2 Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY. 3 Division of Nephrology, Department of Medicine, Columbia University Medical Center, College of Physicians and Surgeons, New York, NY. 4 Department of Quality, NewYork-Presbyterian Hospital, Columbia University Medical Center, New York, NY. 5 Division of Transplantation, Department of Surgery, Columbia University Medical Center, College of Physicians and Surgeons, New York, NY. 6 Address correspondence to: Demetra S. Tsapepas, Pharm.D., B.C.P.S., Department of Pharmacy, NewYork-Presbyterian Hospital, Columbia University Medical Center, 622 West 168th Street, Room VCB, New York, NY.
authors.forename: Demetra S
authors.initials: DS
authors.lastname: Tsapepas
authors.forename: Rodica
authors.initials: R
authors.lastname: Vasilescu
authors.forename: Bekir
authors.initials: B
authors.lastname: Tanriover
authors.forename: Yael
authors.initials: Y
authors.lastname: Coppleson
authors.forename: Yelena
authors.initials: Y
authors.lastname: Rekhtman
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hardy
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Dube
authors.forename: R John
authors.initials: RJ
authors.lastname: Crew
authors.forename: Lloyd E
authors.initials: LE
authors.lastname: Ratner
authors.forename: David J
authors.initials: DJ
authors.lastname: Cohen
authors.forename: Sumit
authors.initials: S
authors.lastname: Mohan
mesh_terms: D000208:Acute Disease; D000328:Adult; D001706:Biopsy; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D007518:Isoantibodies / Q000097:blood*; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009519:New York City / Q000453:epidemiology; D016017:Odds Ratio; D016016:Proportional Hazards Models; D012086:Reoperation; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D007518:Isoantibodies