Journal Article

The Tacrolimus Metabolism Rate Influences Renal Function after Kidney Transplantation

Reuter, Stefan, Pabst, Dirk, Suwelack, Barbara, Pavenstädt, Hermann, Gerth, Hans Ulrich, Hüsing, Anna, Thölking, Gerold, Fortmann, Christian, Koch, Raphael, Kabar, Iyad, Wolters, Heiner

2014

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Analysis / Biology and Life Sciences / Blood levels / Calcineurin / Calcineurin inhibitors / Calcineurin Inhibitors - pharmacokinetics / Cytochrome / Cytomegalovirus / Dosage / Drug dosages / Epidermal growth factor receptors / Female / Glomerular Filtration Rate / Glucocorticoids / Graft Survival / Hospitals / Humans / Immunosuppressive agents / Immunosuppressive Agents - pharmacokinetics / Impact analysis / Infections / Influence / Internal medicine / Kidney - drug effects / Kidney Transplantation / Kidney transplants / Kidneys / Male / Medicine / Medicine and Health Sciences / Metabolism / Middle Aged / Monoclonal antibodies / Mycophenolate mofetil / Mycophenolic acid / Nephrology / Nephropathy / Patients / Physiological aspects / Prednisolone / Prescription drugs / Prospective Studies / Renal function / Renal Insufficiency - surgery / Retrospective Studies / Rheumatology / Risk Factors / Risk management / Tacrolimus / Tacrolimus - pharmacokinetics / Toxicity / Transplantation / Transplants & implants / Treatment Outcome