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Abstract
Fast metabolism of immediate-release tacrolimus (IR-Tac) is associated with decreased kidney function after renal transplantation (RTx) compared to slow metabolizers. We hypothesized, by analogy, that fast metabolism of extended-release tacrolimus (ER-Tac) is associated with worse renal function. We analyzed data from patients who underwent RTx at three different transplant centers between 2007 and 2016 and received an initial immunosuppressive regimen with ER-Tac, mycophenolate, and a corticosteroid. Three months after RTx, a Tac concentration to dose ratio (C/D ratio) < 1.0 ng/ml · 1/mL defined fast ER-Tac metabolism and ≥ 1.0 ng/ml · 1/mL slow metabolism. Renal function (estimated glomerular filtration rate, eGFR), first acute rejection (AR), conversion from ER-Tac, graft and patient survival were observed up to 60-months. 610 RTx patients were divided into 192 fast and 418 slow ER-Tac metabolizers. Fast metabolizers showed a decreased eGFR at all time points compared to slow metabolizers. The fast metabolizer group included more patients who were switched from ER-Tac (p < 0.001). First AR occurred more frequently (p = 0.008) in fast metabolizers, while graft and patient survival rates did not differ between groups (p = 0.529 and p = 0.366, respectively). Calculation of the ER-Tac C/D ratio early after RTx may facilitate individualization of immunosuppression and help identify patients at risk for an unfavorable outcome.
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1 University Hospital of Münster Marienhospital Steinfurt, Department of Internal Medicine and Nephrology, Steinfurt, Germany (GRID:grid.16149.3b) (ISNI:0000 0004 0551 4246); University Hospital of Münster, Division of General Internal Medicine, Nephrology and Rheumatology, Department of Medicine D, Münster, Germany (GRID:grid.16149.3b) (ISNI:0000 0004 0551 4246)
2 University Hospital of Münster Marienhospital Steinfurt, Department of Internal Medicine and Nephrology, Steinfurt, Germany (GRID:grid.16149.3b) (ISNI:0000 0004 0551 4246)
3 University Hospital of Münster, Division of General Internal Medicine, Nephrology and Rheumatology, Department of Medicine D, Münster, Germany (GRID:grid.16149.3b) (ISNI:0000 0004 0551 4246)
4 University of Münster, Institute of Biostatistics and Clinical Research, Münster, Germany (GRID:grid.5949.1) (ISNI:0000 0001 2172 9288)
5 University Hospital Cologne, Department II of Internal Medicine and Center for Molecular Medicine Cologne, Faculty of Medicine, Cologne, Germany (GRID:grid.411097.a) (ISNI:0000 0000 8852 305X)
6 University Hospitals Leuven, Department of Nephrology and Renal Transplantation, Leuven, Belgium (GRID:grid.410569.f) (ISNI:0000 0004 0626 3338)