Monitoring Tacrolimus Trough Concentrations During the First Year After Kidney Transplantation: A National Retrospective Cohort Study

Abstract

Background: There is a lack of data in the literature on the evaluation of tacrolimus (TAC) dosage regimen and monitoring after kidney transplantation (KT) in Kuwait. The aim of the present study was to evaluate TAC dosing in relation to the hospital protocol, the achievement of target TAC trough concentration (C0), the prevalence of TAC side effects (SEs), namely, posttransplant diabetes mellitus (PTDM), denovo hypertension (HTN), and dyslipidemia, and factors associated with the occurrence of these SEs among KT recipients.Methods: A retrospective study was conducted among 298 KT recipients receiving TAC during the first year of PT. Descriptive and multivariate logistic regression analyses were used.Results: The initial TAC dosing as per the local hospital protocol was prescribed for 28.2% of patients. The proportion of patients who had C0 levels within the target range increased from 31.5 to 60.3% during week 1 through week 52. Among patients who did not have HTN, DM, or dyslipidemia before using TAC, 78.6, 35.2, and 51.9% of them were prescribed antihypertensive, antidiabetic, and antilipidemic medications during the follow-up period. Age of ≥40 years was significantly associated with the development of de novo HTN, dyslipidemia, and PTDM (p < 0.05). High TAC trough concentration/daily dose (C0/D) ratio was significantly associated with the development of PTDM (p < 0.05).Conclusion: Less than two-fifths of patients achieved target TAC C0 levels during the first month of PT. Side effects were more common in older patients. These findings warrant efforts to implement targeted multifaceted interventions to improve TAC prescribing and monitoring after KT.

Analysis of risk factors and establishment of a risk prediction model for post-transplant diabetes mellitus after kidney transplantation

“…Tacrolimus-induced PTDM may involve various changes through different mechanisms, including decreased insulin secretion, increased insulin resistance and increased insulin resistance β changes in cell function and peripheral insulin resistance ( Dai et al, 2020 ). A previous study indicated that higher tacrolimus concentration was closely associated with PTDM ( Alghanem et al, 2020 ). It has been reported that tacrolimus concentration > 15–20 ng/mL within the first month post-transplantation was an important risk factor for PTDM ( Ajabnoor et al, 2020 ).…”

Miliary Histoplasmosis in a Renal Transplant Patient

“…Itraconazole inhibits CYP3A4 and P-glycoprotein, resulting in increased tacrolimus concentrations, which increases the potential for adverse effects because of excessive immunosuppression and toxicity (e.g., nephrotoxicity and neurotoxicity) [ 13 , 14 ]. Tacrolimus trough concentrations should be assessed upon the initiation of itraconazole and subsequent dose adjustments to ensure that concentrations are within the narrow therapeutic window [ 15 , 16 ]. Notably, itraconazole oral formulations (e.g., solution, capsule, and tablet) have inherent PK differences and should not be used interchangeably [ 13 ].…”

Analytical and Clinical Validation of Assays for Volumetric Absorptive Microsampling (VAMS) of Drugs in Different Blood Matrices: A Literature Review

“…Table 3 shows the detailed validation results and the missing parameter data of other neutral drugs. Most neutral drugs that underwent a validation study have an LLOQ concentration below the plasma/serum concentration range of their drugs, except for everolimus, perampanel, and sirolimus [ 16 , 53 , 61 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 ]. Everolimus has an LLOQ of 0.02 µg/mL [ 61 ], whereas its concentration range is 0.003–0.008 µg/mL [ 100 ].…”