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Improved Kidney Allograft Function after Early Conversion of Fast IR-Tac Metabolizers to LCP-Tac

Fast tacrolimus (Tac) metabolism is associated with a more rapid decline of renal function after renal transplantation (RTx). Because the pharmacokinetics of LCP-Tac (LCPT) and immediate-release Tac (IR-Tac) differ, we hypothesized that switching from IR-Tac to LCPT in kidney transplant recipients w...

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Autores principales: Thölking, Gerold, Tosun-Koç, Filiz, Jehn, Ulrich, Koch, Raphael, Pavenstädt, Hermann, Suwelack, Barbara, Reuter, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911319/
https://www.ncbi.nlm.nih.gov/pubmed/35268380
http://dx.doi.org/10.3390/jcm11051290
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author Thölking, Gerold
Tosun-Koç, Filiz
Jehn, Ulrich
Koch, Raphael
Pavenstädt, Hermann
Suwelack, Barbara
Reuter, Stefan
author_facet Thölking, Gerold
Tosun-Koç, Filiz
Jehn, Ulrich
Koch, Raphael
Pavenstädt, Hermann
Suwelack, Barbara
Reuter, Stefan
author_sort Thölking, Gerold
collection PubMed
description Fast tacrolimus (Tac) metabolism is associated with a more rapid decline of renal function after renal transplantation (RTx). Because the pharmacokinetics of LCP-Tac (LCPT) and immediate-release Tac (IR-Tac) differ, we hypothesized that switching from IR-Tac to LCPT in kidney transplant recipients would improve the estimated glomerular filtration rate (eGFR), particularly in fast metabolizers. For proof of concept, we performed a pilot study including RTx patients who received de novo immunosuppression with IR-Tac. A Tac concentration-to-dose ratio (C/D ratio) < 1.05 ng/mL·1/mg defined fast metabolizers and ≥1.05 ng/mL·1/mg slow metabolizers one month after RTx. Patients were switched to LCPT ≥ 1 month after transplantation and followed for 3 years. Fast metabolizers (n = 58) were switched to LCPT earlier than slow metabolizers (n = 22) after RTx (2.0 (1.0–253.1) vs. 13.2 (1.2–172.8) months, p = 0.005). Twelve months after the conversion to LCPT, Tac doses were reduced by about 65% in both groups. The C/D ratios at 12 months had increased from 0.66 (0.24–2.10) to 1.74 (0.42–5.43) in fast and from 1.15 (0.32–3.60) to 2.75 (1.08–5.90) in slow metabolizers. Fast metabolizers showed noticeable recovery of mean eGFR already one month after the conversion (48.5 ± 17.6 vs. 41.5 ± 17.0 mL/min/1.73 m², p = 0.032) and at all subsequent time points, whereas the eGFR in slow metabolizers remained stable. Switching to LCPT increased Tac bioavailability, C/D ratio, and was associated with a noticeable recovery of renal function in fast metabolizers. Conversion to LCPT is safe and beneficial early after RTx.
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spelling pubmed-89113192022-03-11 Improved Kidney Allograft Function after Early Conversion of Fast IR-Tac Metabolizers to LCP-Tac Thölking, Gerold Tosun-Koç, Filiz Jehn, Ulrich Koch, Raphael Pavenstädt, Hermann Suwelack, Barbara Reuter, Stefan J Clin Med Article Fast tacrolimus (Tac) metabolism is associated with a more rapid decline of renal function after renal transplantation (RTx). Because the pharmacokinetics of LCP-Tac (LCPT) and immediate-release Tac (IR-Tac) differ, we hypothesized that switching from IR-Tac to LCPT in kidney transplant recipients would improve the estimated glomerular filtration rate (eGFR), particularly in fast metabolizers. For proof of concept, we performed a pilot study including RTx patients who received de novo immunosuppression with IR-Tac. A Tac concentration-to-dose ratio (C/D ratio) < 1.05 ng/mL·1/mg defined fast metabolizers and ≥1.05 ng/mL·1/mg slow metabolizers one month after RTx. Patients were switched to LCPT ≥ 1 month after transplantation and followed for 3 years. Fast metabolizers (n = 58) were switched to LCPT earlier than slow metabolizers (n = 22) after RTx (2.0 (1.0–253.1) vs. 13.2 (1.2–172.8) months, p = 0.005). Twelve months after the conversion to LCPT, Tac doses were reduced by about 65% in both groups. The C/D ratios at 12 months had increased from 0.66 (0.24–2.10) to 1.74 (0.42–5.43) in fast and from 1.15 (0.32–3.60) to 2.75 (1.08–5.90) in slow metabolizers. Fast metabolizers showed noticeable recovery of mean eGFR already one month after the conversion (48.5 ± 17.6 vs. 41.5 ± 17.0 mL/min/1.73 m², p = 0.032) and at all subsequent time points, whereas the eGFR in slow metabolizers remained stable. Switching to LCPT increased Tac bioavailability, C/D ratio, and was associated with a noticeable recovery of renal function in fast metabolizers. Conversion to LCPT is safe and beneficial early after RTx. MDPI 2022-02-26 /pmc/articles/PMC8911319/ /pubmed/35268380 http://dx.doi.org/10.3390/jcm11051290 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Thölking, Gerold
Tosun-Koç, Filiz
Jehn, Ulrich
Koch, Raphael
Pavenstädt, Hermann
Suwelack, Barbara
Reuter, Stefan
Improved Kidney Allograft Function after Early Conversion of Fast IR-Tac Metabolizers to LCP-Tac
title Improved Kidney Allograft Function after Early Conversion of Fast IR-Tac Metabolizers to LCP-Tac
title_full Improved Kidney Allograft Function after Early Conversion of Fast IR-Tac Metabolizers to LCP-Tac
title_fullStr Improved Kidney Allograft Function after Early Conversion of Fast IR-Tac Metabolizers to LCP-Tac
title_full_unstemmed Improved Kidney Allograft Function after Early Conversion of Fast IR-Tac Metabolizers to LCP-Tac
title_short Improved Kidney Allograft Function after Early Conversion of Fast IR-Tac Metabolizers to LCP-Tac
title_sort improved kidney allograft function after early conversion of fast ir-tac metabolizers to lcp-tac
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911319/
https://www.ncbi.nlm.nih.gov/pubmed/35268380
http://dx.doi.org/10.3390/jcm11051290
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