Association of graft survival with tacrolimus exposure and late intra-patient tacrolimus variability in pediatric and young adult renal transplant recipients: an international CTS registry analysis

Adolescent and young adult age is a high-risk window with an alarmingly increased likelihood of premature kidney graft loss due to immunological rejection. Using the large database of the Collaborative Transplant Study, we analyzed whether a more intense and less variable exposure to tacrolimus coul...

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Bibliographic Details
Main Authors: Gold, Annika (Author) , Tönshoff, Burkhard (Author) , Döhler, Bernd (Author) , Süsal, Caner (Author)
Format: Article (Journal)
Language:English
Published: 2020
In: Transplant international
Year: 2020, Volume: 33, Issue: 12, Pages: 1681-1692
ISSN:1432-2277
DOI:10.1111/tri.13726
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1111/tri.13726
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/tri.13726
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Author Notes:Annika Gold, Burkhard Tönshoff, Bernd Döhler & Caner Süsal
Description
Summary:Adolescent and young adult age is a high-risk window with an alarmingly increased likelihood of premature kidney graft loss due to immunological rejection. Using the large database of the Collaborative Transplant Study, we analyzed whether a more intense and less variable exposure to tacrolimus could counteract this young age-related enhanced immunoreactivity. Kidney graft recipients aged 12-23 years (n = 964) with a 1-year tacrolimus trough level between 4.0 and 10.9 ng/ml had a 5-year graft survival rate of 85.1%, significantly better than the poor 66.1% rate in patients with a trough level below 4.0 ng/ml who showed a 2.38-fold increased risk of graft loss in the multivariable analysis (P < 0.001). This association was not apparent in young children aged 0-11 years (n = 455) and less pronounced in adults aged 24-34 years (n = 1466). However, an intra-patient variability of tacrolimus (IPV) trough level ≥1.5 at post-transplant years 1 and 2 was associated with an increased graft loss risk in both 12- to 23-year-old and 0- to 11-year-old recipients (P < 0.001 and P = 0.045). Patients with high IPV made up as many as 30% of kidney graft recipients, indicating that a more intense and less variable exposure to tacrolimus could improve graft survival strongly in this high-risk group.
Item Description:First published: 02 September 2020
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Physical Description:Online Resource
ISSN:1432-2277
DOI:10.1111/tri.13726