*Purpose: The HLA-incompatible (HLAi) barrier has been traversed using desensitization therapies with IVIg, rituximab and/or plasmapheresis, although antibody-mediated rejection (ABMR) continues to be observed in 25-42% cases and constitutes the primary cause of early graft loss. Imlifidase (IdeS) is an IgG endopeptidase which cleaves human IgG into Fc and F(ab)’2 fragments. Previous data (N Engl J Med 2017) demonstrated efficacy in rapidly desensitizing HLA sensitized patients, allowing successful kidney transplantation. Here, we report follow up data up to 3 years on patients transplanted after IdeS desensitization.

*Methods: Sixteen highly-sensitized kidney transplant recipients were desensitized with IdeS 0.24 mg/kg at transplant and alemtuzumab on post-operative day 4, IVIG 2 g/kg on day 7, and rituximab 375 mg/m² on day 14. Follow up data on de novo and rebound DSA generation, death, graft loss, and eGFR were examined.

*Results: Twelve of 16 recipients had a positive flow crossmatch and 14/16 (88%) had DSA at the time of transplant (median sum MFI 8750, IQR: 3750-16250). No patients had DSA immediately following IdeS administration and DSA rebound out to 30 months was generally mild (fig 1). There were seven episodes of ABMR and 8 episodes of cell-mediated rejection (fig 2a). Two graft losses were observed over 31.9 person-years of follow-up, conferring an incidence rate of 6.3 graft losses/100 patient-years. Both graft losses were unrelated to IdeS and developed at 2.6 and 3.2 years after transplant. One death occurred ten months after transplant. The estimated GFR was 60.8 ml/min/1.73 m² (95% CI: 44.2-77.4) at 1 year and 47.5 ml/min/1.73 m² (30.3-64.8) at 3 years (fig 2b).

*Conclusions: IdeS given for desensitization facilitated deceased donor kidney transplantation in highly-sensitized, HLA-incompatible kidney recipients with excellent graft survival out to 3 years.

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