Published online Sep 18, 2026. doi: 10.5500/wjt.122485
Revised: June 27, 2026
Accepted: July 13, 2026
Published online: September 18, 2026
Processing time: 132 Days and 22.1 Hours
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 un
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.
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.
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.
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.
Core Tip: In this large single-center study from the Middle East, pretransplant donor-specific antibodies (DSA) were frequently observed but were not independently associated with rejection or survival after accounting for other factors. Instead, a higher human leukocyte antigen mismatch burden (≥ 7) and poorer early graft function were more closely associated with adverse outcomes. These findings suggest that with current induction strategies, particularly the widespread use of antithymocyte globulin (ATG), the effect of preformed DSA may be less pronounced than traditionally expected. In everyday practice, this highlights the importance of looking beyond antibody status alone and paying closer attention to donor-recipient matching and early graft performance when assessing risk after transplantation. However, the high use of ATG and the relatively short follow-up may have attenuated or delayed the detectable impact of DSA on graft outcomes, particularly late rejection or chronic antibody-mediated injury.