Introduction. The incidence of de novo DSA increases post-KTx. DSA is associated to reduced graft survival likely due to chronic antibody mediated rejection (cAMR). However, this relationship needs clarification as post-KTx DSA is much more common than cAMR. We assessed risk factors for de novo DSA and relationships between DSA, 5 year graft histology and cause of graft loss.

Methods. Included are 638 KTx recipients without DSA at transplant, 63% males, age 53+13, 80% living donor recipients. DSA I/II were measured at post-KTx annual visits. Protocol biopsies were done at 1, 2, 5 and 10 years. 75% thymoglobulin induction, 13% anti-C25 and 9% Alemtuzumab/ steroid free. 93% tacrolimus. Follow up: 90+38 months.

Results. The incidence of positive DSA I increased progressively: 4%, 8%, 12% and 23% at 1, 3, 5 and 8 years post-KTx, respectively. The incidence of positive DSA II (same time points) was higher: 5%, 17%, 33% and 72%. At 5 years, the incidence of DSADQ and DSADR were 28% and 19% (p<0.0001). De novo DSA I related to: Alemtuzumab/steroid free (HR=2.93, p<0.0001), lower year 1 prograf levels (HR=0.77, p=0.001), more HLA mismatches (HR=1.22, p=0.001), re-transplantation (HR=2.25, p=0.003) and acute rejection (HR=1.68, p=0.042) (multivariate). De novo DSA II related to Alemtuzumab/steroid free (HR=2.46, p<0.0001), lower year 1 prograf levels (HR=0.83, p<0.0001), females (HR=1.39, p=0.009) and acute rejection (HR=1.01, p=0.05). De novo DSA (time dependent) related to higher alloimmune losses (DSA I: HR=5.74 (2.29-14.4), p<0.0001; DSA II: HR=5.94 (2.31-15.3), p<0.0001). However, the presence of DSA I or II was poorly predictive of cAMR (positive prediction: 12% and 9%). In fact, only 12% / 9% of DSA I/II positive recipients developed cAMR. Alloimmune losses after 5 years related independently to DSA pre-5 years and to histology at 5 years. DSA II was highly prevalent in grafts with cAMR (92%) but it was prevalent in all other biopsies including normal (33-75%). DSA I/II did not relate to graft loss in recipients without cAMR and it did not relate to non-alloimmune graft loss.

Discussion. DSA, particularly class II, often develops post-KTx. Development of DSA relates to several identifiable risk factors. DSA is associated with cAMR and alloimmune graft loss. However, most patients becoming DSA positive first 5 years do not develop cAMR and do not lose their allograft due to alloimmune mechanisms.

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