22 March 2016 : Original article
Tacrolimus Concentration/Dose Ratio is Associated with Renal Function After Liver Transplantation
Gerold ThölkingABCE, Lea SiatsBC, Christian FortmannBC, Raphael KochCE, Anna HüsingBD, Vito R. CicinnatiDE, Hans Ulrich GerthBCE, Heiner H. WoltersCD, Christoph AnthoniBD, Hermann PavenstädtDE, Barbara SuwelackCE, Hartmut H. SchmidtDE, Iyad KabarDEFDOI: 10.12659/AOT.895898
Ann Transplant 2016; 21:167-179
Abstract
BACKGROUND: The calcineurin inhibitor (CNI) tacrolimus (Tac) is an effective immunosuppressant used after liver transplantation (LTx), but is often associated with CNI nephrotoxicity. Currently, there is no simple clinical predictor for CNI nephrotoxicity after LTx. We hypothesized that the Tac metabolism rate – defined as the blood concentration normalized by its daily dose (the C/D ratio) – is associated with post-LTx renal impairment.
MATERIAL AND METHODS: We analyzed the relationship between the C/D ratio and post-transplant renal function in 179 patients who underwent LTx between 2000 and 2012 and were initially immunosuppressed with Tac, mycophenolate mofetil, and prednisolone. Six months after LTx, 115 patients were categorized into 1 of 2 groups based on their Tac C/D ratio (<1.09 or ≥1.09): fast (n=58) or slow (n=57) metabolizers. The renal function was determined 36 months after LTx using the estimated glomerular filtration rate (eGFR) as described by Cockcroft and Gault.
RESULTS: At the time of LTx there was no statistically significant difference between the eGFR of fast and slow metabolizers. Six months (P=0.016), 12 months (P=0.001), and 36 months (P=0.018) after LTx, fast Tac metabolizers had significantly more impaired renal function than slow metabolizers. Because of a presumption of CNI nephrotoxicity, 32.8% of fast metabolizers and 14.0% of slow metabolizers were switched from Tac to other immunosuppressants (P=0.027).
CONCLUSIONS: In this study, the Tac metabolism rate appears to influence renal function after LTx, suggesting that a C/D ratio of <1.09 is associated with increased CNI nephrotoxicity in LTx recipients.
Keywords: Liver Transplantation, Metabolism, renal insufficiency, Tacrolimus
In Press
Case report
Pulmonary Embolism Following Living Donor Hepatectomy: A Report of 4 Cases and Literature ReviewAnn Transplant In Press; DOI: 10.12659/AOT.946752
Most Viewed Current Articles
03 Jan 2023 : Original article 6,527
Impact of Autologous Stem Cell Transplantation on Primary Central Nervous System Lymphoma in First-Line and...DOI :10.12659/AOT.938467
Ann Transplant 2023; 28:e938467
15 Aug 2023 : Review article 6,222
Free-Circulating Nucleic Acids as Biomarkers in Patients After Solid Organ TransplantationDOI :10.12659/AOT.939750
Ann Transplant 2023; 28:e939750
16 May 2023 : Original article 6,152
Breaking Antimicrobial Resistance: High-Dose Amoxicillin with Clavulanic Acid for Urinary Tract Infections ...DOI :10.12659/AOT.939258
Ann Transplant 2023; 28:e939258
17 Jan 2023 : Original article 5,279
Non-Cryopreserved Peripheral Blood Stem Cell Graft for Autologous Hematopoietic Stem Cell Transplantation i...DOI :10.12659/AOT.938595
Ann Transplant 2023; 28:e938595