Background and aims: The reasons for the increased incidence of de novo anti-HLA donor specific antibodies (DSAs) that is observed after kidney allograft nephrectomy (NTx) are not fully unknown. Two mechanisms have been advocated: (i) at graft loss, DSAs are not detected in the serum because they are fixed on the non-functional transplant, and are released after NTx; (ii) NTx itself is responsible for de novo anti-HLA immunization. The aim of the present study was to test these two hypotheses.

Methods: Seventeen patients have undergone NTx, 4 (3-33) months after graft loss. Immunosuppression had been stopped in all patients at least three months before NTx. Anti-HLA antibodies were assessed in the serum before, and 1, 5, 30, and 90 days after NTx. In addition, fragments of the removed kidney allograft were eluted to characterized intra-graft anti-HLA antibodies. Anti-HLA antibodies were analyzed using the Luminex Single antigen assay.

Results: At NTx, anti-HLA antibodies in the serum were detected in 13 patients. At that time, anti-HLA antibodies that were fixed in the kidney allograft were detected in 11 patients (85%) and positive C4d staining was positive in 9 of the last 11 patients. 22% of reactivity found in graft eluates matched with the donor serological HLA typing. However, this percentage increased to 90% when cross-reactivity against donor's HLA was assessed by epitope analysis. After Ntx, de novo DSAs occurred in 70% of patients. All de novo DSAs were detected ≥ 1 month after NTx. Interestingly, these de novo DSAs were not detected previously in kidney allograft eluates.

Conclusion: Our data suggest that anti-HLA sensitization after NTx is related to the NTx itself rather than to a release of fixed anti-HLA antibodies from the failed kidney.

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