Allosensitization after transplant failure: the role of graft nephrectomy and immunosuppression – a retrospective study

Abstract

There are conflicting data about the role of transplant nephrectomy and immunosuppression withdrawal on the development of allosensitization and the impact on re-transplantation. We divided 109 first graft recipients into two groups according to whether they underwent nephrectomy (NX+, n = 61) or their graft was left in situ (NXÀ, n = 48). Sera were assessed for HLA-A/B/Cw/DR/DQ antibodies at the time of NX/transplant failure and after 3, 6, 12, 24 months. The NX+ group showed a higher rate of donor specific antibody (DSA) and non-DSA human leukocyte antigen (HLA) antibody production at all the time points. Multivariable analysis showed that nephrectomy was a strong, independent risk factor for the development of DSAs after 12 and 24 months (P = 0.005 and 0.008). In the NXÀ group, low tacrolimus levels correlated with DSA formation (AUC 0.817, P = 0.002; best cut-off level 2.9 ng/ml). Analysis with a standardized pool of UK donors showed a more difficult grade of HLA matchability following nephrectomy compared with the NXÀ group. Nephrectomy is followed by the long-term production of DSA and non-DSA HLA antibodies and negatively impacts on the chances of finding a HLA-compatible kidney. Tacrolimus levels ≥3 ng/ml are protective against the development of allosensitization and could facilitate re-transplantation in the NXÀ group. Transplant International 2019; 32: 949-959

Donor-specific antibodies detected by single antigen beads alone can help risk stratify patients undergoing retransplantation across a repeat HLA mismatch

“…29 Besides the presence of an RMM, retransplantation outcomes have also been shown to be related to other clinical characteristics related to primary transplant failure; namely rejection as the cause of failure, longevity of graft and time to retransplantation. [31][32][33] In this study, we have now demonstrated that it is the development of donor specific sensitization to subsequent allografts rather than broadness of sensitization per se which will impact on future outcomes. However, we and others have previously shown that time to retransplantation is likely to affect outcomes due to the development of broad HLA sensitization following allograft failure over time.…”

“…However, we and others have previously shown that time to retransplantation is likely to affect outcomes due to the development of broad HLA sensitization following allograft failure over time. [31][32][33] In this study, we have now demonstrated that it is the development of donor specific sensitization to subsequent allografts rather than broadness of sensitization per se which will impact on future outcomes. This has been shown in other studies analyzing the overall risk of sensitization on allograft outcomes.…”

Memory T‐cell exhaustion and tolerance in transplantation

“…8,9 Lucisano et al describe a single-center retrospective study of patients who underwent nephrectomy before retransplant. 8,9 Lucisano et al describe a single-center retrospective study of patients who underwent nephrectomy before retransplant.…”

“…Retrospective analyses have been done to test whether nephrectomy after failed graft can improve or impede the tolerance of a subsequent renal transplant. 8,9 Lucisano et al describe a single-center retrospective study of patients who underwent nephrectomy before retransplant. Their study revealed that removal of the initial graft leads to an increase in circulating HLA-specific antibodies, an increase in cross-reactivity to other potential donors, and overall decreased chance of finding a future match.…”

“…While patients who kept the original failed graft in situ needed to remain on immunosuppression, these patients did have more success finding subsequent matching allografts and minimizing future rejection. 8 The authors indicate that perhaps the presence of previously grafted tissue could contribute to tolerization of the patient and improve the likelihood of a successful subsequent graft. However, in this study all of the patients who received a nephrectomy were weaned off of immunosuppression after the removal of the graft, while patients who kept the original graft in situ remained immunosuppressed.…”