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. (21st September 2020)

• Record Type: Journal Article
• Authors: Gold, Annika; Tönshoff, Burkhard; Döhler, Bernd; Süsal, Caner
• Is Part Of: Transplant international. Volume 33:Number 12(2020)
• Page Start: 1681
• Page End: 1692
• Publication Date: 2020-09-21
• Subjects: late intra‐patient tacrolimus variability -- pediatrics -- renal allograft survival -- tacrolimus exposure -- young adults; Transplantation of organs, tissues, etc -- Periodicals; 617.95405
• DOI: 10.1111/tri.13726
• Languages: English
• ISSNs: 0934-0874

Abstract

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.