Introduction: Adolescent and young adult age is a high-risk window with an 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.
Materials and Methods: This is a retrospective study of 1,419 0–23-year-old pediatric and young adult renal transplant recipients on whom we had the 1-year tacrolimus trough level information and who were transplanted with a deceased donor kidney between January 1, 2001 and December 31 2017. Patients with multi-organ transplantations, missing follow-up data, graft loss within the first year post-transplant as well as patients on mammalian target of rapamycin-inhibitors were excluded. The patients were followed-up to end of year 5 post-transplant. The upper age limit of 23 years was chosen as previous studies had suggested that renal graft survival in young adults is comparable to those of adolescent recipients. 1,466 24–34-year-old adult renal transplant recipients served as controls. Intra-patient variability (IPV) of tacrolimus trough levels was defined as the largest ratio of the values at year 1 and 2 after transplantation. Mantel Cox log‐rank (with trend) test was used for analysis of the impact of both tacrolimus trough levels as well as IPV of tacrolimus trough levels on graft survival. Multivariable Cox regression was performed to account for the possible influence of confounders.
Results and Discussion: Kidney graft recipients aged 12–23 years (n=964) with a 1-year tacrolimus trough level between 4.0–10.9 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 adult controls aged 24–34 years (n=1,466). 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 12–23- as well as 0–11-year-old recipients (hazard ratio=2.47; P<0.001 and hazard ratio=3.86; P=0.045, respectively). Patients with high IPV made up as many as 30% of kidney graft recipients in all age groups.
Conclusion: Our results indicate that a more intense and less variable exposure to tacrolimus could improve graft survival strongly, especially in adolescents and young adults.