Abstract
High intra-patient variability (IPV) of tacrolimus trough concentrations is increasingly recognized as a predictor of poor long-term outcomes in kidney transplant. However, there is a lack of information regarding the association between tacrolimus IPV and graft outcomes according to immunological risk. We analyzed tacrolimus IPV using the coefficient of variability from months 6–12 after transplantation in 1080 kidney transplant recipients. Patients were divided into two immunological risk groups based on pre-transplant panel reactive antibodies and donor-specific antibodies. High immunological risk was defined as panel reactive antibodies ≥ 20% or the presence of donor-specific antibodies. The effects of tacrolimus IPV on graft outcomes were significantly different between low and high immunological risk patients. A multivariable Cox regression model confirmed that high tacrolimus IPV was an independent risk factor for graft failure in the high risk group (HR, 2.90; 95% CI, 1.42–5.95, P = 0.004). In the high risk group, high tacrolimus IPV was also significantly associated with increased risk of antibody-mediated rejection (P = 0.006). In contrast, death-censored graft survival and antibody-mediated rejection in the low immunological risk group was not significantly different by tacrolimus IPV. High tacrolimus IPV significantly increases the risk of graft failure and antibody-mediated rejection in patients with high immunological risk.
Highlights
High intra-patient variability (IPV) of tacrolimus trough concentrations is increasingly recognized as a predictor of poor long-term outcomes in kidney transplant
We evaluate the association between tacrolimus IPV and graft outcomes and rejection in low- and high immunological risk patients
Patients were divided into low- and high immunological risk groups according to peak panel reactive antibodies (PRA) and presence of donor-specific anti-human leukocyte antigens (HLA) antibodies (DSA; high immunological risk was defined as PRA ≥ 20% or the presence of DSA)
Summary
High intra-patient variability (IPV) of tacrolimus trough concentrations is increasingly recognized as a predictor of poor long-term outcomes in kidney transplant. Patients were divided into two immunological risk groups based on pre-transplant panel reactive antibodies and donor-specific antibodies. The effects of tacrolimus IPV on graft outcomes were significantly different between low and high immunological risk patients. In the high risk group, high tacrolimus IPV was significantly associated with increased risk of antibody-mediated rejection (P = 0.006). Death-censored graft survival and antibody-mediated rejection in the low immunological risk group was not significantly different by tacrolimus IPV. High tacrolimus IPV significantly increases the risk of graft failure and antibodymediated rejection in patients with high immunological risk. Immunological risk of individual patients is a key determinant for tailored immunosuppressive treatment[16] Variables Female, n (%) Age, years Body mass index, kg/m2 Mismatch HLA-A, B, DR 1–2 3–4 5–6 Peak %PRA, median (IQR) Re-transplant, n (%) Dialysis vintage, months Deceased donor, n (%) Female donor, n (%) Donor age, years Induction agent, n (%) No Basiliximab Anti-thymocyte globulin Mean TAC IPV, CV% High TAC IPV, n (%) Mean TAC concentration, ng/mL Dose of TAC, mg/day TAC concentration to dose ratio TAC formulation Twice daily TACOnce daily TACCo-medication HMG CoA reductase inhibitor Proton pump inhibitor Diuretics Anticoagulants or antiplatelet drugs
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