Impact of preformed donor specific antibodies on rejection, allograft survival and mortality in kidney transplant recipients: An Australian registry study

Introduction: Preformed donor-specific antibodies (DSA) increase the risk of antibody-mediated rejection (AMR) and allograft loss following kidney transplantation, with risk associated with DSA strength (mean fluorescence intensity (MFI)). Australian outcomes have not been evaluated in an allocation system favouring MFI <4,000 DSA deceased donor transplantation.
Methods: Retrospective cohort study of adult kidney transplant recipients in Australia (2014-2023) using linked ANZDATA and OrganMatch data. DSA status was defined by Luminex single antigen bead testing, characterised by Human Leukocyte Antigen class, MFI, and presence in current versus peak sera. Outcomes were time to first rejection, allograft and patient survival, analysed using adjusted Cox proportional hazards models.
Results: Of 9471 recipients, 1814 (19.1%) were DSA positive. DSA positive recipients more commonly had prior transplantation, deceased donor kidneys, and longer dialysis duration (Table 1). DSA were 42.6% class I only, 35.0% class II only, and 22.4% both; 87.3% had MFI <4000 and 53.5% were current.

Rejection was more common in DSA positive recipients (24.2% vs 19.8% DSA negative, p<0.001), occurred earlier (median 24 vs 38 days, p=0.028) and was more frequently AMR (46.0% vs 39.4%, p=0.014). DSA positivity was associated with early rejection risk: aHR 1.85 (95% CI 1.50–2.30) at one month, 1.46 (1.26–1.68) at three months, 1.28 (1.11–1.47) at six months, and 1.06 (0.90–1.25) at one year, with no significant association beyond one year. T-cell depleting induction was associated with reduced rejection risk (aHR 0.65, 95% CI 0.50–0.84).
AMR was the dominant driver of allograft loss irrespective of DSA status (DSA+/AMR+ 68.6% vs DSA−/AMR+ 77.7%) (Figure 1). 

On univariable analysis, DSA positivity was associated with allograft loss (HR 1.34, 95% CI 1.19–1.50); this was attenuated in the adjusted model (aHR 1.09, 95% CI 0.97–1.23) but re-emerged on exclusion of dialysis duration (aHR 1.17, 95% CI 1.04–1.32). Among DSA positive recipients, allograft loss risk was associated only with strong peak MFI (≥4,000; aHR 1.59, 95% CI 1.09–2.32).
DSA positivity was not associated with mortality after adjustment (aHR 1.07, 95% CI 0.92-1.23).
Conclusion: Kidney transplantation outcomes were comparable between DSA positive and DSA negative recipients, supporting transplantation with low-level DSA within current allocation parameters over deferral. T-cell depleting induction was associated with reduced rejection risk in DSA positive recipients. AMR was strongly associated with allograft loss, with peak immunodominant MFI ≥4,000 a subgroup at high risk. These findings support prospective evaluation of MFI-stratified risk assessment and earlier transplantation to minimise comorbidity accrual.