A 36-year-old female presented for a third renal transplant after two previous cadaveric transplants (2000, 2006). She had been on maintenance dialysis since 2019. Pre-transplant workup with a live-related donor showed a positive CDC crossmatch. Single Antigen Bead (SAB) testing revealed no Class I DSA but high MFI Class II DSA: • DQA1: 01:03/01:02/02:01/01:04/02:01/01:04/01:01 (MFI=18,705-14,423) • DQB1: 06:01/06:03/06:04/06:02 (MFI=18,705-13,092) She underwent rituximab, plasmapheresis, and IVIG, but Class II DSA remained high. Further desensitization included: • Daratumumab (16 mg/kg IV, weekly) + Plerixafor (0.16 mg/kg SC, 11 hrs prior) (4 doses) • Four sessions of immunoadsorption Her CDC crossmatch became negative, and Class II MFI decreased: • DQA1: 14,506-7,781 • DQB1: 14,506-8,466 Despite persistent Class II DSA, the transplant was conducted following patient's informed consent. Pre-transplant immunosuppression included tacrolimus, MMF, and prednisolone, with ATG induction (3 mg/kg). Postoperatively, she had immediate graft function. Unexpectedly, Class II DSA became undetectable, possibly due to the prolonged effect of Daratumumab. Two-year follow-up showed stable graft function. BK viremia was managed with immunosuppression reduction, leflunomide, and IVIG. This case highlights Daratumumab’s potential in HLA desensitization, warranting larger studies to validate its use.