title: The tacrolimus metabolism rate influences renal function after kidney transplantation.
abstract: The effective calcineurin inhibitor (CNI) tacrolimus (Tac) is an integral part of the standard immunosuppressive regimen after renal transplantation (RTx). However, as a potent CNI it has nephrotoxic potential leading to impaired renal function in some cases. Therefore, it is of high clinical impact to identify factors which can predict who is endangered to develop CNI toxicity. We hypothesized that the Tac metabolism rate expressed as the blood concentration normalized by the dose (C/D ratio) is such a simple predictor. Therefore, we analyzed the impact of the C/D ratio on kidney function after RTx. Renal function was analyzed 1, 2, 3, 6, 12 and 24 months after RTx in 248 patients with an immunosuppressive regimen including basiliximab, tacrolimus, mycophenolate mofetil and prednisolone. According to keep the approach simple, patients were split into three C/D groups: fast, intermediate and slow metabolizers. Notably, compared with slow metabolizers fast metabolizers of Tac showed significantly lower estimated glomerular filtration rate (eGFR) values at all the time points analyzed. Moreover, fast metabolizers underwent more indication renal biopsies (p = 0.006) which revealed a higher incidence of CNI nephrotoxicity (p = 0.015) and BK nephropathy (p = 0.024) in this group. We herein identified the C/D ratio as an easy calculable risk factor for the development of CNI nephrotoxicity and BK nephropathy after RTx. We propose that the simple C/D ratio should be taken into account early in patient's risk management strategies.
authors.affiliation: Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, Münster, Germany.
authors.forename: Gerold
authors.initials: G
authors.lastname: Thölking
authors.affiliation: Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, Münster, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Fortmann
authors.affiliation: Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany.
authors.forename: Raphael
authors.initials: R
authors.lastname: Koch
authors.affiliation: Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, Münster, Germany.
authors.forename: Hans Ulrich
authors.initials: HU
authors.lastname: Gerth
authors.affiliation: Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, Münster, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Pabst
authors.affiliation: Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, Münster, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Pavenstädt
authors.affiliation: Department of Transplant Medicine, University Hospital of Münster, Münster, Germany.
authors.forename: Iyad
authors.initials: I
authors.lastname: Kabar
authors.affiliation: Department of Transplant Medicine, University Hospital of Münster, Münster, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Hüsing
authors.affiliation: Department of General Surgery, University Hospital of Münster, Münster, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Wolters
authors.affiliation: Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, Münster, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Reuter
authors.affiliation: Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, Münster, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Suwelack
mesh_terms: D000328:Adult; D065095:Calcineurin Inhibitors / Q000493:pharmacokinetics; D005260:Female; D005919:Glomerular Filtration Rate; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics; D007668:Kidney / Q000187:drug effects*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000601:surgery; D012189:Retrospective Studies; D012307:Risk Factors; D016559:Tacrolimus / Q000493:pharmacokinetics*; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016559:Tacrolimus