There is evidence showing the importance of reaching immunosuppressant target concentrations as soon as possible. The aim of this study was to evaluate the relationship between tacrolimus trough concentrations within the first week after transplantation and the rate of acute rejection. In this descriptive-analytic study, we included 57 renal transplant patients receiving tacrolimus as the primary immunosuppressive drug. After univariate analysis, donor age, duration of hospital stay, and creatinine clearance (third month) showed significant differences between rejecters and nonrejecters. In addition, mean tacrolimus trough concentrations on day 5, day 7, mean of days 1-7, and mean of days 5-7 were found to be significantly lower in rejecters (P = 0.009, P = 0.012, P = 0.006, and P = 0.035, respectively). Receiver operating characteristic curve analysis with tacrolimus trough concentrations measured on days 5 and 7 was able to discriminate between patients with and without acute rejection (P = 0.028 and P = 0.048 after Bonferroni correction). The tacrolimus trough concentration with the best sensitivity-specificity balance was 9.3 ng/mL on day 5 and 8.7 ng/mL on day 7. In the Kaplan-Meier analysis, patients with tacrolimus trough concentrations below 9.3 mg/mL on day 5 showed a lower survival time without acute rejection (P = 0.048 after correction) in comparison with patients with tacrolimus trough concentrations above this concentration. After logistic regression, we obtained a model relating rejection with sex, donor age, and tacrolimus trough concentrations on day 5 (P = 0.004). No significant relationship between tacrolimus trough concentrations and delta creatinine clearance from week 1 to month 3 was obtained. These results confirm that tacrolimus trough concentrations during the first week are an important predictor of acute rejection. Therefore, it is critical to reach target blood concentrations of tacrolimus as soon as possible to improve allograft survival.
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http://dx.doi.org/10.1097/FTD.0b013e3181a8f02a | DOI Listing |
PeerJ
December 2024
Department of Pharmacy, Nanjing Drum Tower Hospital the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.
Background: Microbiota-derived toxins indoxyl sulfate and hippuric acid were previously reported to be associated with altered pharmacokinetics of the immunosuppressant tacrolimus in liver transplant recipients, and ABC transporter proteins are likely to be involved in the transport of such substances, but the role has not been elucidated. The aim of this study was to assess the retention of indoxyl sulfate and hippuric acid in the plasma of liver transplantation subjects carrying different genotypes of and (changes in transporter activity due to genetic variation), and to explore whether genetic variation is involved in altering the relationship between microbe-derived toxins and tacrolimus pharmacokinetics.
Methods: Liver transplantation subjects treated with the immunosuppressive regimen tacrolimus, corticosteroids, and mycophyolate mofetil were included and divided into normal renal function group and chronic kidney disease group.
J Med Case Rep
December 2024
Department of Kidney and Transplant Services, Princess Alexandra Hospital, Brisbane, Australia.
Background: Kidney transplant recipients with severe acute respiratory syndrome-coronavirus-2 infection have an increased risk of severe disease and mortality. Nirmaltrevir/ritonavir (Paxlovid) is an effective oral disease-modifying therapy that has been shown to reduce risk of progression to severe disease in high-risk, nonhospitalized adults. However, owing to the potential for serious drug-drug interactions owing to ritonavir-induced inhibition of the CYP3A enzyme, this drug is not suitable option for transplant recipients with mild-moderate severe acute respiratory syndrome-coronavirus-2 infection.
View Article and Find Full Text PDFDrug Metab Pers Ther
December 2024
Department of Clinical Pharmacology, National Centre Chalbi Belkahia of Pharmacovigilance, Tunis, Tunisia.
Objectives: While the existing literature extensively covers the topic of tacrolimus variability, it remains crucial to gather data that are tailored to the Tunisian population. Our primary goal was to assess the variability in tacrolimus bioavailability using the Cp(0)/weight dosage ratio in Tunisian kidney transplant patients. We also aimed to determine the correlations between blood trough level (Cp(0)) and the area under the concentration-time curve (AUC0-12 h) in this cohort.
View Article and Find Full Text PDFNefrologia (Engl Ed)
December 2024
Department of Nephrology, Puerta del Mar University Hospital, Cádiz, Spain.
Introduction: In kidney transplant (KT) recipients diabetes mellitus (DM) are associated with an increased mortality and a poorer graft survival. Glucagon-like peptide 1 receptor agonists (GLP1-RA) have demonstrated cardiovascular and renal benefits in the general population. However, there is lacking evidence in KT recipients.
View Article and Find Full Text PDFTransplant Proc
December 2024
From the Senior Department of Hepatology, the Fifth Medical Center, Chinese PLA General Hospital, Beijing, China. Electronic address:
Background: Tacrolimus is a substrate of CYP 3A5; to reduce the rate of liver injury and rejection in liver transplant (LT) recipients, it is feasible to optimize the administration of tacrolimus by adding CYP gene polymorphism.
Methods: We divided 151 LT recipients randomly into an optimization group and a control group. All were tested routinely for clinical indicators such as FK506 trough concentration and biochemistry, and their complications and survival were observed.
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