The Impact of Withdrawal of Maintenance Immunosuppression and Graft Nephrectomy on HLA Sensitization and Calculated Chance of Future Transplant

Abstract

BackgroundThe development of HLA antibodies towards a failing renal allograft is a barrier to retransplantation. This study aimed to compare the formation of HLA donor-specific antibodies (DSA) in patients undergoing graft nephrectomy and in those with a failed graft left in situ who had maintenance immunosuppression (IS) stopped, and assess the relative impact of IS cessation and graft nephrectomy on future relative chance of transplant (R-CoT).MethodsA single-center retrospective study of patients with failed grafts between 2005 and 2015 was performed. Samples were tested for DSA pre-IS wean, post-IS wean, and post-IS cessation. Nephrectomy patients additionally had samples tested for DSA before and after nephrectomy. Calculated reaction frequency (cRF) was determined at each timepoint and entered into the UK Organ Donation and Transplant R-CoT calculator.ResultsForty-one patients were included in the study: 24 with nephrectomy and 17 with a failed graft in situ. Patient demographics and duration of IS wean were similar between groups. There was a higher rate of blood transfusion (54% vs 24%) in nephrectomy patients. In patients whose graft remained in situ, cRF rose from 13% pre-IS wean to 40% post-IS wean and 62% after IS cessation. This equated to a reduction in mean R-CoT from 54% to 46% at 5 years. In patients undergoing nephrectomy mean cRF rose from 31% pre-IS wean to 69% post-IS wean and 89% post-IS cessation. Mean R-CoT fell from 54% to 42% at 5 years.ConclusionsA stepwise increase in cRF with reduced chance of transplant was observed in both groups as IS was withdrawn, with a similar pattern irrespective of graft nephrectomy. Calculated reaction frequency was higher in the nephrectomy group. The risks and benefits of stopping IS need to be carefully considered on an individual basis to maximize chance of future transplant.

Immunosuppression with Calcineurin Inhibitor after Renal Transplant Failure Inhibits Allosensitization

“…DSAs were also measured before and after graft nephrectomy in those in which it was performed. An increase in antibody titer was observed in those patients with IS withdrawal, and this titer was higher in patients with graft nephrectomy [32].…”

The omission of the “wet” pre‐transplant crossmatch in renal transplant centres in Scotland

“…In cases of previous transplant, whether the graft is in situ or not, the Luminex SAB testing is always performed on a day of transplant sample before kidney implantation. This is because HLA antibody profiles of patients with previous donor material still present can change rapidly as immunosuppression is tapered or stopped . For all sensitised patients a wet XM is performed retrospectively. Sensitised patients where analysis of recent or historic Luminex SAB data indicates the presence of a potential HLA‐DSA.…”

“…The recommendation is to perform a final “wet” pre‐transplant XM within 14 days prior to the transplant date. If the patient is sensitised or their antibody profile changes during the period between the vXM and final XM, for example due to changes in immunosuppression, an intermediate “wet” crossmatch may take place. The patient has antibodies reactive with donor mismatches with cumulative MFI <5000 (+/−) or that may represent reactivity against denatured antigen and the vXM is positive. The recommendation will be to perform a full “wet” XM to assess compatibility further.…”

“…This is because HLA antibody profiles of patients with previous donor material still present can change rapidly as immunosuppression is tapered or stopped. 26 For all sensitised patients a wet XM is performed retrospectively.…”

“…The recommendation is to perform a final "wet" pre-transplant XM within 14 days prior to the transplant date. If the patient is sensitised or their antibody profile changes during the period between the vXM and final XM, for example due to changes in immunosuppression, 26 an intermediate "wet" crossmatch may take place. 2.…”