Relationship between 2-Hour Tacrolimus Concentrations and Clinical Outcomes in Long Term Kidney Transplantation.

Jeffrey Yin,Robert Steiner,Linda Awdishu,Tammy Hsu,Janice S Kerr

doi:10.3390/pharmacy8020060

Jeffrey Yin, Robert Steiner + Show 3 more

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https://doi.org/10.3390/pharmacy8020060

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Abstract

Background: Tacrolimus is routinely monitored using trough concentrations, however, recent data have suggested that area under the curve (AUC) provides better correlation with toxicity and efficacy. Area under the curve is cumbersome to measure, but studies have demonstrated that surrogate time points such as 2-hour concentrations are well correlated with AUC. Methods: This is a single center, retrospective study of adult kidney transplant recipients with 2-hour tacrolimus concentrations measured over three years post-transplant. The primary outcome was to determine the difference in serum creatinine (Scr) in those with 2-hour tacrolimus concentrations greater than 20 ng/mL versus those less than or equal to 20 ng/mL. Results: A total of 150 kidney transplant recipients were included. The mean Scr and glomerular filtration rate were 1.49 ± 1.01 mg/dL and 59 ± 23.2 mL/min/1.73 m2, respectively, for the entire cohort. The rate of donor specific antibody formation was 2% and 8% experienced biopsy-proven rejection. The rate of cytomegalovirus viremia was 2% and BK viremia was 13%. There was no significant difference in kidney function over 36 months for the groups specified a priori. Conclusions: Long-term outcomes of maintaining tacrolimus 2-hour concentrations over 20 ng/mL is favorable with minimal opportunistic infections.

Highlights

Tacrolimus (FK) is a calcineurin inhibitor most commonly used in immunosuppressive regimens after kidney transplantation [1]
Studies have demonstrated that while trough concentrations may correlate with toxicity [8,10], area under the curve (AUC) is a stronger predictor of acute rejection [11,12,13]
Patients are stratified into the high risk group as opposed to the low risk group if the patient had any of the following criteria: panel reactive antibodies (PRA) ≥20%, positive donor specific antibodies (DSA), if kidneys are from donors after cardiac death (DCD), if delayed graft function (DGF)

Summary

Introduction

Tacrolimus (FK) is a calcineurin inhibitor most commonly used in immunosuppressive regimens after kidney transplantation [1] It has a narrow therapeutic index with high inter- and intra-individual variability, necessitating the need for therapeutic drug monitoring [2,3]. Studies have demonstrated that while trough concentrations may correlate with toxicity [8,10], area under the curve (AUC) is a stronger predictor of acute rejection [11,12,13]. Tacrolimus is routinely monitored using trough concentrations, recent data have suggested that area under the curve (AUC) provides better correlation with toxicity and efficacy. Area under the curve is cumbersome to measure, but studies have demonstrated that surrogate time points such as 2-hour concentrations are well correlated with AUC. The mean Scr and glomerular filtration rate were 1.49 ± 1.01 mg/dL and

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