A multicenter prospective cohort study evaluating impact of an active delisting strategy to enable kidney transplantation in waitlisted candidates with cPRA >= 99.9%
In a multicenter Spanish cohort, a careful HLA-antigen delisting strategy enabled kidney transplantation for highly sensitized candidates with cPRA >= 99.9%, granting access to transplant at the cost of a substantial early antibody-mediated rejection risk but reasonable short-term graft survival.
Background
Kidney transplant candidates with a calculated panel reactive antibody (cPRA) of 99.9% or higher have little realistic access to a fully HLA-compatible donor and can remain on dialysis for many years. Because preformed donor-specific antibody (DSA) does not always cause antibody-mediated rejection, delisting selected lower-risk HLA antigens has been proposed to widen the donor pool while accepting some immunologic risk.
Study design
This was a prospective cohort across four Spanish transplant centers (May 2022 to August 2023). HLA antigens were delisted in steps based on mean fluorescence intensity (MFI < 5,000, then < 10,000, with special handling of anti-HLA-DP and DRB3/4/5), serum dilution response, and complement-binding activity, aiming to lower cPRA to 99.0% or below while avoiding the most deleterious specificities.
Key findings
Among 48 patients delisted after a median 5.6 years on the waiting list, cPRA fell to a median 98.3%, and 30 (62.5%) received an acceptable donor offer a median of 98 days after delisting. Eighteen patients with negative crossmatches were transplanted directly without imlifidase desensitization; 16 of these had at least one preformed DSA. At one year, antibody-mediated rejection occurred in 7 of 16 cases (43.7%), with graft survival of 87.5%.
Clinical implications
Delisting can meaningfully expand transplant access for the most highly sensitized candidates without requiring novel desensitization agents. However, the high rate of acute antibody-mediated rejection means the approach demands careful antigen selection, informed patient consent, and close post-transplant immunologic monitoring.
Category
Transplant
Source
Kidney International
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