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

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+/-).

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.

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).

Persistent de novo DSA, after kidney transplantation, is associated with higher MFI and increased risk of ABMR and GF.