Time-Varying Determinants of Graft Failure in Pediatric Kidney Transplantation in Europe
Ferran Coens, Noël Knops, Ineke Tieken, Serge Vogelaar, Andreas Bender, Jon Jin Kim, Kai Krupka, Lars Pape, Ann Raes, Burkhard Tönshoff, Agnieszka Prytula,- Transplantation
- Nephrology
- Critical Care and Intensive Care Medicine
- Epidemiology
Background:
Little is known about the time-varying determinants of kidney graft failure in children.
Methods:
We performed a retrospective study of primary pediatric kidney transplant recipients (<18 years) from the Eurotransplant registry (1990-2020). Piece-wise exponential additive mixed models were applied to analyze time-varying recipient, donor, and transplant risk factors. Primary outcome was death-censored graft failure.
Results:
We report on 4528 kidney transplantations, of which 68% with deceased and 32% with living donor. 1638 recipients experienced graft failure, and 168 died with a functioning graft. Between 2011-2020, the 5-year graft failure risk was 10% for deceased donor and 4% for living donor kidney transplant recipients. Risk of graft failure decreased 5-fold from 1990 to 2020. The association between living donor transplantation and the lower risk of graft failure was strongest in the first month posttransplant (aHR:0.58, 95%CI:0.46-0.73) and remained statistically significant until 12 years posttransplant. Risk factors for graft failure in the first 2 years were deceased donor age <12 or >46 years, potentially recurrent kidney disease, and PRA>0%. Other determinants of graft failure included dialysis prior to transplantation (until 5 years posttransplant), HLA-mismatch 2-4 (0-15 years posttransplant), HLA-mismatch 5-6 (2-12 years posttransplant), and hemodialysis (8-14 years posttransplant). Recipients >11 years at transplantation had a higher risk of graft failure 1-8 years posttransplant compared to other age groups, whereas young recipients had a lower risk throughout follow-up. Analysis of the combined effect of posttransplant time and recipient age showed a higher rate of graft failure during the first 5 years posttransplant in adolescents compared with young transplant recipients. In contrast to deceased donors <12 years, deceased donor age >46 years was consistently associated with a higher graft failure risk.
Conclusions:
We report a long-term inverse association between living donor kidney transplantation and the risk of graft failure. The determinants of graft failure varied with time. There was a significant cumulative effect of adolescence and time posttransplant. The “ideal donor age window” was dependent on time posttransplant.