Impact of pretransplant donor-specific antibodies and human leukocyte antigen mismatches on graft and patient outcomes: A cohort from Saudi Arabia.

Abstract

Background: Pretransplant donor-specific antibodies (DSA) are frequently encountered in kidney transplant recipients, but their combined effect with human leukocyte antigen (HLA) mismatches on post-transplant outcomes is as yet not fully understood, particularly in Middle Eastern populations.

Aim: To evaluate the effect of pretransplant DSA, HLA mismatches, and early graft function on acute rejection, graft loss, and patient survival, using detailed immunologic profiling and longitudinal follow-up to inform transplant management strategies.

Methods: We conducted a retrospective study of 260 kidney transplant recipients with available pretransplant HLA typing and DSA assessment. Patients were followed for graft function, acute rejection, graft loss, and mortality. Multivariable logistic regression was used to identify predictors of preformed DSA and acute rejection, and Cox proportional hazards models were applied to evaluate factors associated with a composite outcome of acute rejection, graft loss, or death. Event-free survival was assessed using Kaplan-Meier analysis.

Results: Acute rejection occurred in 10 patients (3.8%). In exploratory multivariable analyses, a higher HLA mismatch burden and suboptimal early graft function at 4 months post-transplant were associated with acute rejection; however, these findings should be interpreted cautiously because of the limited number of events. Pretransplant DSA was present in a subset of patients but was not independently associated with outcomes after adjustment for HLA mismatch and early graft function. A mismatch burden ≥ 7, reduced early graft function, and a history of sensitizing events were associated with a higher risk of the composite outcome. Kaplan-Meier analysis showed significantly lower event-free survival among patients with ≥ 7 HLA mismatches, while reduced early graft function further improved risk discrimination over time.

Conclusion: Pretransplant DSA and HLA mismatch burden were both associated with post-transplant outcomes; however, the prognostic signal was largely driven by HLA mismatch and early graft function rather than DSA alone. A mismatch burden ≥ 7 was associated with reduced event-free survival, and early graft function further stratified risk. Induction therapy with antithymocyte globulin may have reduced the clinical impact of preformed DSA in sensitized recipients.