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Clinical Trial
. 2020 Oct;42(5):702-709.
doi: 10.1097/FTD.0000000000000772.

No Apparent Influence of Nonadherence on Tacrolimus Intrapatient Variability in Stable Kidney Transplant Recipients

Sumit R M Gokoel  1 , Tom C Zwart  2 , Dirk Jan A R Moes  2 , Paul J M van der Boog  1 , Johan W de Fijter  1
Affiliations
Clinical Trial

No Apparent Influence of Nonadherence on Tacrolimus Intrapatient Variability in Stable Kidney Transplant Recipients

Sumit R M Gokoel et al. Ther Drug Monit. 2020 Oct.

Abstract

Background: High intrapatient variability (IPV) in tacrolimus exposure has been associated with an increased risk of graft rejection and graft loss. It has been suggested that medication nonadherence has high impact on IPV. The objective of this study is to assess the relationship between tacrolimus IPV and medication nonadherence in stable kidney transplant recipients.

Methods: This study was conducted within the Reducing Renal Function Deterioration trial (Netherlands Trial Register: NTR7256), which included stable kidney transplant recipients. Nonadherence was assessed quantitatively by electronic monitoring (EM) and qualitatively using the composite adherence score (CAS) consisting of patient self-reporting (Immunosuppressant Therapy Adherence Scale), a physician report, and the tacrolimus trough concentrations (C0). IPV in tacrolimus C0 and area under the concentration-time curves (AUCs) was evaluated at 5 and 3 sampling instances, respectively.

Results: Data of 64 kidney transplant recipients (43 males, 21 females; mean age 53.6 years), mean time post-transplantation 5.4 years, were collected. Mean missed tacrolimus intake was 7% (0.3%-13.4%) based on EM, missing one intake every 2 weeks. Based on the CAS, 68.9% of the patients were categorized as nonadherent. The mean IPV was 17.9% (4.4%-65.3%) and 20.2% (2.5%-51.6%) for tacrolimus C0 and AUCs, respectively. The nonadherence data displayed a nonparametric distribution, with nonadherence scores mostly in the lower ranges. There was no significant difference in the mean IPV between adherent and nonadherent patients. There were no differences in EM, CAS, physician report, or time-in-therapeutic range, but patients with a low AUC IPV showed a slightly higher Immunosuppressant Therapy Adherence Scale score than those with a high AUC IPV (P = 0.035).

Conclusions: There was no apparent relationship between IPV and nonadherence in this motivated kidney transplant recipient population, with one missed tacrolimus dose every 2 weeks.

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References

    1. Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transpl. 2009;9(suppl 3):S1–S155.
    1. Shuker N, van Gelder T, Hesselink DA. Intra-patient variability in tacrolimus exposure: causes, consequences for clinical management. Transpl Rev. 2015;29:78–84.
    1. Kuypers DRJ. Intrapatient variability of tacrolimus exposure in solid organ transplantation: a novel marker for clinical outcome. Clin Pharmacol Ther. 2020;107:347–358.
    1. van Gelder T. Within-patient variability in immunosuppressive drug exposure as a predictor for poor outcome after transplantation. Kidney Int. 2014;85:1267–1268.
    1. Goodall DL, Willicombe M, McLean AG, et al. High intrapatient variability of tacrolimus levels and outpatient clinic nonattendance are associated with inferior outcomes in renal transplant patients. Transpl Direct. 2017;3:e192.

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