Optimal blood levels of (extended-release) tacrolimus in living donor kidney transplantation to prevent de novo donor-specific antibody production: A retrospective cohort study

Hiramitsu, Takahisa; Tomosugi, Toshihide; Futamura, Kenta; Okada, Manabu; Nishihira, Morikuni; Goto, Norihiko; Ichimori, Toshihiro; Narumi, Shunji; Kobayashi, Takahiro; Uchida, Kazuharu; Watarai, Yoshihiko

doi:10.1016/j.intimp.2020.107038

Cited by 3 publications

(2 citation statements)

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“…Hiramitsu et al, who evaluated the impact of TAC C 0 on prevention of dnDSA production in adult living-related kidney transplant recipients, reported that mean TAC C 0 concentration was significantly higher in the dnDSA negative than in the dnDSA positive patients receiving triple-drug immunosuppressive protocol (4.60 ng/mL, interquartile 4.05–5.14 vs. 3.85 ng/mL, interquartile 3.53–4.18; p = 0.001. The authors also compared the trough concentration of MPA (mycophenolic acid), and found no difference between two groups, which suggested the major role of TAC in preventing the dnDSA production [ 17 ]. Davis et al have evaluated the impact of mean TAC C 0 on the risk of dnDSA in a cohort of 538 adult patients during the first year after kidney transplantation, and found that mean TAC C 0 < 8 ng/mL was associated with dnDSA generation at 6 months (odds ratio [OR] 2.51, 95% CI, 1.32–4.79, p = 0.005) and 12 months (OR 2.32, 95% CI.…”

Section: Discussionmentioning

confidence: 99%

“…The suboptimal range of C 0 TAC blood concentration in long-term follow-up has been identified as one of risk factors relevant for dnDSA production. Data from studies in living-related adult transplant patients treated with the extended-releas e tacrolimus (combined with various drugs in a triple maintenance protocol) demonstrated significant difference between mean C 0 TAC values in the dnDSA-positive and -negative patients (4.88 vs. 3.69; p = 0.023) [ 17 ]. Blood concentration of the regular immunosuppressive drugs has been reported as an important risk factor also in pediatric transplant patients [ 12 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Cumulative Effect of Standard Triple Immunosuppression on Prevention of De Novo Donor Specific Antibodies (dnDSA) Production in Children after Kidney Transplantation—A Retrospective and Prospective Study

et al. 2021

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De novo Donor Specific Antibodies (dnDSA) are associated with inferior graft outcomes. Standard immunosuppression is expected to prevent dnDSA production in low-risk patients. We have evaluated a cumulative effect of a triple immunosuppression (CNI/MMF/Pred), as well as TAC concentration and coefficient of variation on the incidence of dnDSA production. Overall, 67 transplanted patients were evaluated in retrospective (dnDSA for-cause; n = 29) and prospective (dnDSA by protocol; n = 38) groups. In the retrospective group, the eGFR value at first dnDSA detection (median interval—4.0 years post-transplant) was 41 mL/min/1.73 m2; 55% of patients presented biopsy-proven cAMR, and 41% lost the graft within next 2.4 years. Patients from the prospective group presented 97% graft survival and eGFR of 76 mL/min/1.73 m2 at 2 years follow-up, an overall incidence of 21% of dnDSA and 18% of acute (T cell) rejection. None of the patients from the prospective group developed cAMR. Median value of Vasudev score within 2 years of follow-up was not significantly higher in dsDSA negative patients, while median value of TAC C0 > 1–24 months post-transplant was 7.9 in dnDSA negative vs. 7.1 ng/mL in dnDSA positive patients (p = 0.008). Conclusion: dnDSA-negative patients presented a higher exposure to tacrolimus, while not to the combined immunosuppression.

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Section: Discussionmentioning

confidence: 99%