title: Influence of tacrolimus metabolism rate on renal function after solid organ transplantation.
abstract: The calcineurin inhibitor (CNI) tacrolimus (TAC) is an integral part of the immunosuppressive regimen after solid organ transplantation. Although TAC is very effective in prevention of acute rejection episodes, its highly variable pharmacokinetic and narrow therapeutic window require frequent monitoring of drug levels and dose adjustments. TAC can cause CNI nephrotoxicity even at low blood trough levels (4-6 ng/mL). Thus, other factors besides the TAC trough level might contribute to CNI-related kidney injury. Unfortunately, TAC pharmacokinetic is determined by a whole bunch of parameters. However, for daily clinical routine a simple application strategy is needed. To address this problem, we and others have evaluated a simple calculation method in which the TAC blood trough concentration (C) is divided by the daily dose (D). Fast TAC metabolism (C/D ratio < 1.05) was identified as a potential risk factor for an inferior kidney function after transplantation. In this regard, we recently showed a strong association between fast TAC metabolism and CNI nephrotoxicity as well as BKV infection. Therefore, the TAC C/D ratio may assist transplant clinicians in a simple way to individualize the immunosuppressive regimen.
authors.affiliation: Gerold Thölking, Hans Ulrich Gerth, Katharina Schuette-Nuetgen, Stefan Reuter, Division of General Internal Medicine, Nephrology and Rheumatology, Department of Medicine D, University Hospital of Münster, 48149 Münster, Germany.
authors.forename: Gerold
authors.initials: G
authors.lastname: Thölking
authors.affiliation: Gerold Thölking, Hans Ulrich Gerth, Katharina Schuette-Nuetgen, Stefan Reuter, Division of General Internal Medicine, Nephrology and Rheumatology, Department of Medicine D, University Hospital of Münster, 48149 Münster, Germany.
authors.forename: Hans Ulrich
authors.initials: HU
authors.lastname: Gerth
authors.affiliation: Gerold Thölking, Hans Ulrich Gerth, Katharina Schuette-Nuetgen, Stefan Reuter, Division of General Internal Medicine, Nephrology and Rheumatology, Department of Medicine D, University Hospital of Münster, 48149 Münster, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schuette-Nuetgen
authors.affiliation: Gerold Thölking, Hans Ulrich Gerth, Katharina Schuette-Nuetgen, Stefan Reuter, Division of General Internal Medicine, Nephrology and Rheumatology, Department of Medicine D, University Hospital of Münster, 48149 Münster, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Reuter
keywords: Kidney; Liver; Metabolism; Tacrolimus; Transplantation