Introduction: Tacrolimus (Tac) is an integral part of the immunosuppressive regimen after renal transplantation (RTx). A fast Tac metabolism rate defined as the Tac blood trough concentration (C) divided by the daily dose (D) is associated with the development of renal dysfunction. Thus, we hypothesize that the Tac metabolism rate impacts on survival of patients during a 5 year follow-up.

Patients and methods: RTx recipients treated with an initial Tac based immunosuppressive regimen with mycophenolate mofetil, prednisolone and an induction with basiliximab were included. Patients with a Tac C/D ratio 3 months after RTx <1.05 ng/ml*1/mg were characterized as fast metabolizers, ≥1.05 ng/ml*1/mg as slow metabolizers according to our previous studies.

Results: Fast Tac metabolizers (n=101) had a significantly reduced patient survival rate compared with slow metabolizers (n=187) 5 years after RTx (87.1% vs. 95.2%; P=0.025). Main causes of death were cardiovascular events, followed by infections in both groups. Interestingly, renal function (estimated glomerular filtration rate, eGFR) in fast metabolizers was continuously lower compared with slow metabolizers (eGFR after 4 years: 46.9±17.9 vs. 52.4±18.9 ml/min/1.73m[sup2]; P=0.029).

Conclusion: Fast Tac metabolism is strongly associated with a reduced survival rate of patients during a 5 yr follow-up. Therefore, these patients may profit from alternative immunosuppressive regimen or concepts.

CITATION INFORMATION: Thölking G, Steinke J, Schuette-Nuetgen K, Pavenstädt H, Suwelack B, Reuter S. Influence of Tacrolimus Metabolism Rate on Patients' Survival After Renal Transplantation. Am J Transplant. 2017;17 (suppl 3).

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