Influence of a low-dose tacrolimus protocol on the appearance of de novo donor-specific antibodies during 7 years of follow-up after renal transplantation

Abstract

Background Tacrolimus (TAC) is a key immunosuppressant drug for kidney transplantation (KTx). However, the optimal serum trough level of TAC for good long-term outcomes remains unclear. This study aimed to investigate the relationship between the maintenance TAC trough level and the appearance of de novo donor-specific anti-human leukocyte antigen (HLA) antibodies (dnDSAs). Methods A total of 584 KTx recipients were enrolled in this study, of whom 164 developed dnDSAs during the follow-up period and 420 did not. Results We found no significant relationship between TAC trough level during the follow-up period and dnDSA incidence. Patients who developed dnDSAs had a significantly greater number of HLA-A/B/DR mismatches (3.4 ± 1.3 versus 2.8 ± 1.5; P < 0.001), were more likely to have preformed DSAs (48.2% versus 27.1%; P < 0.001) and showed poor allograft outcome. Conclusions There was no clear relationship between TAC trough level and dnDSA incidence for KTx recipients whose TAC trough levels were kept within the narrow range of 4–6 ng/mL during the immunosuppression maintenance period.

Virtual crossmatching and epitope analysis in kidney transplantation: What the physician involved in kidney transplantation should know?

“…33,34 De novo DSA could impact rejection rate and graft survival more strongly than preformed DSA, and the impact of anti-HLA-A, -B, -DR, and -DQ antibodies are well recognized, like those that are performed. 35 Similar to a preformed antibody, de novo non-DSA did not affect graft outcome. [36][37][38] Despite limited HLA-C data, Willicombe reported that de novo DSA against HLA-C loci were associated with antibody-mediated rejection and transplant glomerulopathy, but not graft loss.…”

“…Anti‐HLA‐DQ antibodies are among the most frequent anti‐HLA antibodies that emerge after transplantation 33,34 . De novo DSA could impact rejection rate and graft survival more strongly than preformed DSA, and the impact of anti‐HLA‐A, ‐B, ‐DR, and ‐DQ antibodies are well recognized, like those that are performed 35 . Similar to a preformed antibody, de novo non‐DSA did not affect graft outcome 36–38 .…”

A 39-year-old male who received living kidney from his 62-year-old father, blood group matched and CDC cross match all negative, having acute cell mediated rejection 5 hours after transplant due to low Tacrolimus Trough level: A case report

“…However, there was no clear relationship between Tacrolimus trough level and dnDSA incidence for kidney transplant recipients whose Tacrolimus trough levels were kept within the narrow range of 4-6 ng/mL during the immunosuppression maintenance period. (Unagami et al, 2021) Tacrolimus has large intrapatient variation (IPV) due to many factors affecting the pharmacokinetics of Tac such as food intake, liver function, renal function, time after transplantation, co-medication,etc. It was reported as poor sign; high intrapatient variability in Tacrolimus concentrations was strongly associated with an increased frequency of deviation from the suggested therapeutic range and an increased number of infection (E. Kim et al, 2020).…”

Lowering maintenance immune suppression in elderly kidney transplant recipients; connecting the immunological and clinical dots

“…Most of the studies have shown a cumulative increase in the percentage of transplant patients who develop de novo DSA in the initial years after transplantation. The cumulative incidence appears to plateau after 5–10 years, along with the risk for ABMR due to de novo DSA ( 89 , 90 ). This corresponds with the clinical data that, long after transplantation (>10–15 years), recipients rarely have a newly diagnosed ABMR.…”