Transplant outcomes after de novo donor specific antibody (DSA) development correlate with persistence of DSA

This is the authors' abstract. We don't add key points for this paper.

BACKGROUND: The OuTSMART trial confirmed de novo DSAs were associated with an increased risk of graft loss and rejection. In this post-hoc analysis, outcomes were analysed in 132 patients who had a DSA at the point of randomisation and compared between patients who had persistent DSA (DSA+/+) with those in whom the DSA was not detected on subsequent samples (DSA+/-). METHODS: Serial serum samples were collected post-enrolment until 2016. Those who had their final visit after 2018, had repeat HLA antibody testing ≥32 months post-randomisation. 115 of the 132 DSA+ patients had 2 or more samples available for analysis. 39/115 patients were persistently DSA+ and in 76/115 the DSA became undetectable at 12-32 months post enrolment. RESULTS: Both groups were well matched in sex, ethnicity, immunosuppression, and DSA status at transplant. The total Mean Fluorescence Intensity (MFI) of baseline DSA was significantly higher in the DSA+/+ vs DSA+/- (11,568 v 6518, P < 0.01) with a predominance of class II HLA. Significantly higher rates of antibody mediated rejection (ABMR) and death censored graft failure (GF) were seen in DSA+/+ vs in DSA+/- (15.4 % v 2.6 %, P = 0.02 and 20.5 % v 6.6 %, P = 0.03 respectively). In Cox regression analysis, persistent DSA and having both HLA classes were associated with increased risk of ABMR (HR 6.05, CI 1.2-30.0, P = 0.03 and HR 14.7, CI 1.33-162, P = 0.03 respectively). Additionally, persistent DSA was associated with higher GF rates (HR 3.4, 1.1-10.4, P = 0.03). CONCLUSIONS: Persistent de novo DSA, after kidney transplantation, is associated with higher MFI and increased risk of ABMR and GF.