This analysis aims to identify appropriate de novo DSA (dnDSA) screening points and delineate the post-transplant (txp) scenarios preceding dnDSA development to aid in clinical understanding and therapeutic decision making.

Methods: All pre-txp DSA negative, HLA-mismatched primary renal txp patients transplanted between 3/99 and 12/10 (n=341) were included if they developed dnDSA post-txp (n=107). Serum was collected pre-txp and post-txp at 1, 3, 6, 9, 12 months and bi-annually, thereafter. The sera were retrospectively tested for HLA IgG antibodies via LABScreen single antigen bead assay.

Results: 107 patients (31%) were found to develop dnDSA over the 3 -14 years of post-txp follow-up. dnDSA development was highest early post-txp (first 24 months post-txp) compared to late post-transplant (>24 months post-txp) (Figs A&B). Specifically, dnDSA was highest in the first 6 months post-txp and rates declining thereafter. When investigating post-txp events that preceded dnDSA, we determined that 37% of dnDSA had a pre-dnDSA history for infection (especially polyoma or cytomegalovirus (BKV or CMV) infection). dnDSA preceeded by BKV or CMV was 3-fold higher in the first 24 months post-txp. Non-adherence (documented and suspected) was found in 17% of dnDSA cases overall with rates 2-fold higher later (>24 months) post-txp (Figs C&D). Overall, 39% of total dnDSA cases had no significant events prior to dnDSA. Actual 3-year post-dnDSA survival (n=99) in those with pre-dnDSA BKV, CMV, or non-adherence was significantly poorer (Fig, p=0.04).

Conclusion: Overall these findings indicate that (1) most dnDSA occur in the first 6-months post-txp, (2) Early dnDSA is related to infection especially BKV and CMV, (3) late dnDSA is more commonly related to non-adherence and (4) dnDSA following non-adherence or BKV/CMV results in significantly poorer outcomes.

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