title: Re-Examining Risk of Repeated HLA Mismatch in Kidney Transplantation.
abstract: Kidney retransplantation is a risk factor for decreased allograft survival. Repeated mismatched HLA antigens between first and second transplant may be a stimulus for immune memory responses and increased risk of alloimmune damage to the second allograft. Historical data identified a role of repeated HLA mismatches in allograft loss. However, evolution of HLA testing methods and a modern transplant era necessitate re-examination of this role to more accurately risk-stratify recipients. We conducted a contemporary registry analysis of data from 13,789 patients who received a second kidney transplant from 1995 to 2011, of which 3868 had one or more repeated mismatches. Multivariable Cox proportional hazards modeling revealed no effect of repeated mismatches on all-cause or death-censored graft loss. Analysis of predefined subgroups, however, showed that any class 2 repeated mismatch increased the hazard of death-censored graft loss, particularly in patients with detectable panel-reactive antibody before second transplant (hazard ratio [HR], 1.15; 95% confidence interval [95% CI], 1.02 to 1.29). Furthermore, in those who had nephrectomy of the first allograft, class 2 repeated mismatches specifically associated with all-cause (HR, 1.30; 95% CI, 1.07 to 1.58) and death-censored graft loss (HR, 1.41; 95% CI, 1.12 to 1.78). These updated data redefine the effect of repeated mismatches in retransplantation and challenge the paradigm that repeated mismatches in isolation confer increased immunologic risk. We also defined clear recipient categories for which repeated mismatches may be of greater concern in a contemporary cohort. Additional studies are needed to determine appropriate interventions for these recipients.
authors.affiliation: Division of Nephrology and Multiorgan Transplant Program, Department of Medicine and HLA Laboratory, Laboratory Medicine Program, University Health Network, University of Toronto, Toronto, Ontario, Canada;
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Tinckam
authors.affiliation: Division of Nephrology, Department of Medicine, St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada; and.
authors.forename: Caren
authors.initials: C
authors.lastname: Rose
authors.affiliation: Department of Medicine and Surgery, Thomas E. Starzl Transplant Institute, University of Pittsburgh Medical Center and Kidney Transplant Program, Pittsburgh, Pennsylvania.
authors.forename: Sundaram
authors.initials: S
authors.lastname: Hariharan
authors.affiliation: Division of Nephrology, Department of Medicine, St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada; and jgill@providencehealth.bc.ca.
authors.forename: John
authors.initials: J
authors.lastname: Gill
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000601:surgery; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D012086:Reoperation; D012189:Retrospective Studies; D018570:Risk Assessment; D014181:Transplantation Immunology; D055815:Young Adult
chemical_list: D006680:HLA Antigens
keywords: chronic allograft failure; kidney transplantation; renal transplantation; transplant nephrectomy; transplant outcomes; transplantation