Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Gashi, A.
Comparison of Tacrolimus Formulations in Kidney Transplant Recipients
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2024. pp. 74
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Eller Kathrin
- Kirsch Alexander
- Altmetrics:
- Abstract:
- Introduction: The calcineurin-inhibitor tacrolimus is a standard immunosuppressive agent in kidney transplantation. It is currently available in different formulations, each with a distinct pharmacokinetic profile. Our aim was to evaluate any differences in outcome depending on the tacrolimus formulation, which was prescribed de novo after kidney transplantation. Methods: For this study fifty-six kidney transplant recipients who received Prograf® and thirty-two kidney transplant recipients who received Envarsus® for induction were included. Study-visits were predefined to take place at one week, two months and twelve months post-transplantation. Routine follow-up checks over the first three months post-transplantation provided additional data. Graft rejections were diagnosed following indication biopsy. Cytomegalovirus and BK polyomavirus infections were identified using blood PCR tests. Tacrolimus intra-patient variability and time in target range were calculated in four-week intervals for the first three months post-transplantation. Furthermore, tacrolimus fast metabolizers were identified using concentration-to-dose ratio. Results: Two and twelve months post-transplantation median creatinine was lower (1.35 ± 0.51; p = 0.02 and 1.36 ± 0.55, p = 0.046, respectively) and mean eGFR was higher (54.93 ± 17.05; p = 0.07 and 55.53 ± 16.38; p = 0.06) in the Envarsus® treatment group.A total of 18 acute graft rejections occurred during follow-up, 3 of them were borderline rejections. A trend wise lower rate of graft rejection and higher rate of BK polyomavirus viremia was noticed in the Envarsus® group. This difference was not statistically significant. Fast metabolizers showed a significantly higher risk of acute graft rejection regardless of treatment group (HR 4.5; CI 95% 1.4 – 14.4; p = 0.01). Fast metabolizers in the Prograf® group showed a significantly higher risk of acute graft rejection (HR 5.0; 1.3 – 20.3; p = 0.02), this effect was blunted in the Envarsus® treatment group (HR 2.72; CI 95% 0.1 – 28.5; p = 0.45).Treatment groups did not differ regarding intra-patient variability. Patients in the Envarsus® group demonstrated a significantly higher time in target range at month two post-transplantation. Conclusion: Induction with de novo Envarsus® decreased rejection risk in fast-metabolizer phenotypes potentially due to improved pharmacokinetic profile. The observation of trend wise lower rejection rate and higher BK polyomavirus viremia incidence may reflect a stronger immunosuppressive effect despite targeting similar trough levels with de novo Envarsus®. Further biological effect analysis is needed to identify markers potentially guiding immunosuppression.