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Increasing Time in Therapeutic Range of Tacrolimus in the First Year Predicts Better Outcomes in Living-Donor Kidney Transplantation.

ABSTRACT: Background: The aim of the present study was to investigate the impact of time in therapeutic range TTR on long-term outcomes of living kidney transplants. Methods: We included 1,241 living kidney transplants and randomized them into development and validation cohorts with a ratio of 2:1. The tacrolimus TTR percentage was calculated by linear interpolation with a target range (5-10 ng/ml months 0-3, 4-8 ng/ml months 4-12). The optimal TTR cutoff was estimated by the receiver operating characteristic curve analysis on the basis of acute rejection (AR) within 12 months in the development cohort. Outcomes were analyzed between patients with high TTR and low TTR in the development and validation cohorts, respectively. The TTR was also compared with other tacrolimus measures. Results: The optimal TTR cutoff value was 78%. In the development cohort, patients with TTR > 78% had significantly higher rejection- and infection-free survival. TTR < 78% was an independent risk factor for AR (OR: 2.97, 95%CI: 1.82-4.84) and infection (OR: 1.55, 95%CI: 1.08-2.22). Patient and graft survival were significantly higher in those with TTR>78%, and TTR<78% was associated with graft loss (OR: 3.2, 95%CI: 1.38-7.42) and patient death (OR: 6.54, 95%CI: 1.34-31.77). These findings were confirmed in the validation cohort. Furthermore, we divided all included patients into a high and low TTR group. TTR was more strongly associated with patient and graft survival than mean level, standard deviation, and intrapatient variability (IPV). Conclusions: Increasing the TTR of tacrolimus in the first year was associated with improved long-term outcomes in living kidney transplants, and TTR may be a novel valuable strategy to monitor tacrolimus exposure.

SUBMITTER: Song T

PROVIDER: S-EPMC6933438 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Increasing Time in Therapeutic Range of Tacrolimus in the First Year Predicts Better Outcomes in Living-Donor Kidney Transplantation.

Song Turun T Yin Saifu S Jiang Yamei Y Huang Zhongli Z Liu Jinpeng J Wang Zhiling Z Li Linde L Zeng Jun J Fan Yu Y Wang Xianding X Li Xingxing X Lin Tao T

Frontiers in immunology 20191220

<b>Background:</b> The aim of the present study was to investigate the impact of time in therapeutic range TTR on long-term outcomes of living kidney transplants. <b>Methods:</b> We included 1,241 living kidney transplants and randomized them into development and validation cohorts with a ratio of 2:1. The tacrolimus TTR percentage was calculated by linear interpolation with a target range (5-10 ng/ml months 0-3, 4-8 ng/ml months 4-12). The optimal TTR cutoff was estimated by the receiver operat ...[more]

PMID: 31921171

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Project description:Acute kidney injury (AKI) is a frequent complication after living donor liver transplantation (LDLT), and is associated with increased mortality. However, the association between intraoperative oliguria and the risk of AKI remains uncertain for LDLT. We sought to determine the association between intraoperative oliguria alone and oliguria coupled with hemodynamic derangement and the risk of AKI after LDLT. We evaluated the hemodynamic variables, including mean arterial pressure, cardiac index, and mixed venous oxygen saturation (SvO₂). We reviewed 583 adult patients without baseline renal dysfunction and who did not receive hydroxyethyl starch during surgery. AKI was defined using the Kidney Disease Improving Global Outcomes criteria according to the serum creatinine criteria. Multivariable logistic regression analysis was performed with and without oliguria and oliguria coupled with a decrease in SvO₂. The performance was compared with respect to the area under the receiver operating characteristic curve (AUC). Intraoperative oliguria <0.5 and <0.3 mL/kg/h were significantly associated with the risk of AKI; however, their performance in predicting AKI was poor. The AUC of single predictors increased significantly when oliguria was combined with decreased SvO₂ (AUC 0.72; 95% confidence interval (CI) 0.68⁻0.75 vs. AUC of oliguria alone 0.61; 95% CI 0.56⁻0.61; p < 0.0001; vs. AUC of SvO₂ alone 0.66; 95% CI 0.61⁻0.70; p < 0.0001). Addition of oliguria coupled with SvO₂ reduction also increased the AUC of multivariable prediction (AUC 0.87; 95% CI 0.84⁻0.90 vs. AUC with oliguria 0.73; 95% CI 0.69⁻0.77; p < 0.0001; vs. AUC with neither oliguria nor SvO₂ reduction 0.68; 95% CI 0.64⁻0.72; p < 0.0001). Intraoperative oliguria coupled with a decrease in SvO₂ may suggest the risk of AKI after LDLT more reliably than oliguria alone or decrease in SvO₂ alone. Intraoperative oliguria should be interpreted in conjunction with SvO₂ to predict AKI in patients with normal preoperative renal function and who did not receive hydroxyethyl starch during surgery.

Dataset Information

Increasing Time in Therapeutic Range of Tacrolimus in the First Year Predicts Better Outcomes in Living-Donor Kidney Transplantation.

Publications

Increasing Time in Therapeutic Range of Tacrolimus in the First Year Predicts Better Outcomes in Living-Donor Kidney Transplantation.

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