title: Intermediate-term graft loss after renal transplantation is associated with both donor-specific antibody and acute rejection.
abstract: BACKGROUND
  Renal transplant recipients with de novo DSA (dDSA) experience higher rates of rejection and worse graft survival than dDSA-free recipients. This study presents a single-center review of dDSA monitoring in a large, multi-ethnic cohort of renal transplant recipients.
  
  
  METHODS
  The authors performed a nested case-control study of adult kidney and kidney-pancreas recipients from July 2007 through July 2011. Cases were defined as dDSA-positive whereas controls were all DSA-negative transplant recipients. DSA were determined at 1, 3, 6, 9, and 12 months posttransplant, and every 6 months thereafter.
  
  
  RESULTS
  Of 503 recipients in the analysis, 24% developed a dDSA, of whom 73% had dDSA against DQ antigen. Median time to dDSA was 6.1 months (range 0.2-44.6 months). After multivariate analysis, African American race, kidney-pancreas recipient, and increasing numbers of human leukocyte antigen mismatches were independent risk factors for dDSA. Recipients with dDSA were more likely to suffer an acute rejection (AR) (35% vs. 10%, P<0.001), an antibody-mediated AR (16% vs. 0.3%, P<0.001), an AR ascribed to noncompliance (8% vs. 2%, P=0.001), and a recurrent AR (6% vs. 1%, P=0.002) than dDSA-negative recipients. At a median follow-up of 31 months, the death-censored actuarial graft survival of dDSA recipients was worse than the DSA-free cohort (P=0.002). Yet, for AR-free recipients, there was no difference in graft survival between cohorts (P=0.66).
  
  
  CONCLUSIONS
  Development of dDSA was associated with an increased incidence of graft loss, yet the detrimental effect of dDSA was limited in the intermediate term to recipients with AR.
authors.affiliation: 1 Department of Pharmacy, The Methodist Hospital, Houston, TX. 2 Department of Surgery, The Methodist Hospital, Houston, TX. 3 Department of Pathology and Genomic Medicine, The Methodist Hospital Research Institute, Houston, TX. 4 Address correspondence to: Jennifer M. DeVos, Pharm.D, B.C.P.S., Department of Pharmacy, The Methodist Hospital, 6565 Fannin Street DB1-09, Houston, TX 77030.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Devos
authors.forename: Ahmed Osama
authors.initials: AO
authors.lastname: Gaber
authors.forename: Larry D
authors.initials: LD
authors.lastname: Teeter
authors.forename: Edward A
authors.initials: EA
authors.lastname: Graviss
authors.forename: Samir J
authors.initials: SJ
authors.lastname: Patel
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Land
authors.forename: Linda W
authors.initials: LW
authors.lastname: Moore
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Knight
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D044383:Black People; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology* / Q000208:ethnology / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006630:Hispanic or Latino; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016035:Pancreas Transplantation; D012307:Risk Factors; D013997:Time Factors; D014019:Tissue Donors; D014180:Transplantation; D044465:White People; D001741:Black or African American
chemical_list: D000906:Antibodies; D006680:HLA Antigens