1. Within-Patient Variability in Tacrolimus Blood Levels Predicts Kidney Graft Loss and Donor-Specific Antibody Development.
- Author
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Rodrigo E, Segundo DS, Fernández-Fresnedo G, López-Hoyos M, Benito A, Ruiz JC, de Cos MA, and Arias M
- Subjects
- Adult, Aged, Female, Histocompatibility Testing, Humans, Male, Middle Aged, Immunosuppressive Agents blood, Isoantibodies biosynthesis, Kidney Transplantation, Tacrolimus blood, Tissue Donors
- Abstract
Background: Lack of adherence to immunosuppressive drugs is a risk factor for development of de novo donor-specific antibodies (dnDSA) and can contribute to antibody-mediated rejection and graft loss. Moreover, nonadherence is the main determinant of immunosuppressive drug level variability. High intrapatient variability of tacrolimus relates to a worse outcome in transplant recipients through unknown mechanisms. We hypothesized that a high within-patient variability of tacrolimus could increase the rate of dnDSA development and contribute to further death-censored graft loss (DCGL)., Methods: We included 310 adult renal transplants receiving twice-daily tacrolimus throughout their first posttransplant year, with (1) at least 3 blood trough levels available to calculate coefficient of variation (CV) from month 4 to 12, (2) graft survival longer than 1 year, and (3) absence of pretransplant DSA. The dnDSA were analyzed in sera at 1, 3, and 5 years and around 6 month before the last follow-up visit or graft loss by single-antigen beads., Results: During the follow-up, 53 patients lost their graft excluding death. A total of 116 patients (37.4%) had a CV greater than 30% and 39 (12.6%) developed dnDSA. Coefficient of variation greater than 30% (hazards ratio, 2.613; 95% confidence interval, 1.361-5.016; P = 0.004) independently related to DCGL. Acute rejection, re-transplant and CV greater than 30% (hazards ratio, 2.925; 95% confidence interval, 1.473-5.807; P = 0.002) were the only variables related to dnDSA development by Cox regression analysis., Conclusions: Tacrolimus level variability is a strong risk factor for dnDSA development and DCGL. Variability must be added to the current monitoring of kidney transplant recipients due to its relationship with adherence and to graft outcome.
- Published
- 2016
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