Early Determination of Tacrolimus Concentration–Dose Ratio Identifies Risk of Allograft Loss in Kidney Transplantation
Introduction: Fast tacrolimus–metabolizing kidney transplant recipients (KTRs) (i.e., tacrolimus trough-level/total daily dose [C0/D < 1.05]) have poorer allograft function; however, their identification in a real-life setting is challenging. We investigated the reproducibility of tacrolimus meta...
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Elsevier
2025-05-01
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| Series: | Kidney International Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024925001032 |
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| author | Christophe Masset Marine Lorent Clarisse Kerleau Claire Garandeau Aurélie Houzet Simon Ville Diego Cantarovich Gilles Blancho Magali Giral Jacques Dantal Gilles Blancho Julien Branchereau Diego Cantarovich Agnès Chapelet Jacques Dantal Florent Delbos Clément Deltombe Lucile Figueres Charles Ronsin Thibault Letellier Clémence Petit Claire Garandeau Magali Giral Caroline Gourraud-Vercel Laurent Nicolet Christine Kandel-Aznar Ismaël Chelghaf Clarisse Kerleau Christophe Masset Aurélie Meurette Karine Renaudin Simon Ville Alexandre Walencik |
| author_facet | Christophe Masset Marine Lorent Clarisse Kerleau Claire Garandeau Aurélie Houzet Simon Ville Diego Cantarovich Gilles Blancho Magali Giral Jacques Dantal Gilles Blancho Julien Branchereau Diego Cantarovich Agnès Chapelet Jacques Dantal Florent Delbos Clément Deltombe Lucile Figueres Charles Ronsin Thibault Letellier Clémence Petit Claire Garandeau Magali Giral Caroline Gourraud-Vercel Laurent Nicolet Christine Kandel-Aznar Ismaël Chelghaf Clarisse Kerleau Christophe Masset Aurélie Meurette Karine Renaudin Simon Ville Alexandre Walencik |
| author_sort | Christophe Masset |
| collection | DOAJ |
| description | Introduction: Fast tacrolimus–metabolizing kidney transplant recipients (KTRs) (i.e., tacrolimus trough-level/total daily dose [C0/D < 1.05]) have poorer allograft function; however, their identification in a real-life setting is challenging. We investigated the reproducibility of tacrolimus metabolic status during the first months after transplantation and its association with long-term allograft outcomes. Methods: All KTRs between 2000 and 2019 with a functional allograft at 1 month and receiving tacrolimus in our center were included. Fast or slow tacrolimus metabolizers were classified according to the time spent with a C0/D < 1.05 (> 75% = High, < 25% = Low) at various time points posttransplantation. We first determined the earliest accurate time for patient categorization by investigating C0/D variability during the first months. Second, a multivariate cause-specific Cox model studying allograft outcomes was performed in groups identified by their status determined from the earliest accurate timepoint after transplantation. Results: Among 1979 patients included in the analysis, 2 months was the earliest accurate timepoint to determine High patients (85% of High patients identified at 2 months remained High long-term, Brier score = 0.06). Multivariate analysis revealed that High patients determined at 2 months (n = 499) had a significantly higher risk of allograft loss (cause-specific hazard ratio [CS-HR] = 2.00, 95% confidence interval [CI] = 1.48–2.69) and allograft rejection (CS-HR = 1.71, 95% CI = 1.15–2.54) than Low patients after adjustment for confounding factors. Moreover, allograft function was lower in High patients (46.7 vs. 52.9 ml/min, at 3 years, P < 0.0001) with a higher proportion of chronic vascular lesions at 1 year. Conclusion: C0/D is a simple and pragmatic tool capable of identifying patients at risk of rejection and allograft failure as early as the second month posttransplantation. |
| format | Article |
| id | doaj-art-d7ad8b6aff5146ac8c660156683dc1d9 |
| institution | Kabale University |
| issn | 2468-0249 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
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| series | Kidney International Reports |
| spelling | doaj-art-d7ad8b6aff5146ac8c660156683dc1d92025-08-20T03:47:10ZengElsevierKidney International Reports2468-02492025-05-011051428144010.1016/j.ekir.2025.02.014Early Determination of Tacrolimus Concentration–Dose Ratio Identifies Risk of Allograft Loss in Kidney TransplantationChristophe Masset0Marine Lorent1Clarisse Kerleau2Claire Garandeau3Aurélie Houzet4Simon Ville5Diego Cantarovich6Gilles Blancho7Magali Giral8Jacques Dantal9Gilles BlanchoJulien BranchereauDiego CantarovichAgnès ChapeletJacques DantalFlorent DelbosClément DeltombeLucile FigueresCharles RonsinThibault LetellierClémence PetitClaire GarandeauMagali GiralCaroline Gourraud-VercelLaurent NicoletChristine Kandel-AznarIsmaël ChelghafClarisse KerleauChristophe MassetAurélie MeuretteKarine RenaudinSimon VilleAlexandre WalencikService de Néphrologie et Immunologie Clinique, Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France; Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes Université, INSERM, Institute of Transplantation Urology and Nephrology, CHU Nantes, Nantes, France; Correspondence: Christophe Masset, Center for Research in Transplantation and Translational Immunology, 30 boulevard Jean-Monnet, Nantes Cedex, France.Service de Néphrologie et Immunologie Clinique, Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, FranceService de Néphrologie et Immunologie Clinique, Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, FranceService de Néphrologie et Immunologie Clinique, Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, FranceService de Néphrologie et Immunologie Clinique, Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, FranceService de Néphrologie et Immunologie Clinique, Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France; Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes Université, INSERM, Institute of Transplantation Urology and Nephrology, CHU Nantes, Nantes, FranceService de Néphrologie et Immunologie Clinique, Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, FranceService de Néphrologie et Immunologie Clinique, Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France; Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes Université, INSERM, Institute of Transplantation Urology and Nephrology, CHU Nantes, Nantes, FranceService de Néphrologie et Immunologie Clinique, Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France; Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes Université, INSERM, Institute of Transplantation Urology and Nephrology, CHU Nantes, Nantes, FranceService de Néphrologie et Immunologie Clinique, Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France; Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes Université, INSERM, Institute of Transplantation Urology and Nephrology, CHU Nantes, Nantes, FranceIntroduction: Fast tacrolimus–metabolizing kidney transplant recipients (KTRs) (i.e., tacrolimus trough-level/total daily dose [C0/D < 1.05]) have poorer allograft function; however, their identification in a real-life setting is challenging. We investigated the reproducibility of tacrolimus metabolic status during the first months after transplantation and its association with long-term allograft outcomes. Methods: All KTRs between 2000 and 2019 with a functional allograft at 1 month and receiving tacrolimus in our center were included. Fast or slow tacrolimus metabolizers were classified according to the time spent with a C0/D < 1.05 (> 75% = High, < 25% = Low) at various time points posttransplantation. We first determined the earliest accurate time for patient categorization by investigating C0/D variability during the first months. Second, a multivariate cause-specific Cox model studying allograft outcomes was performed in groups identified by their status determined from the earliest accurate timepoint after transplantation. Results: Among 1979 patients included in the analysis, 2 months was the earliest accurate timepoint to determine High patients (85% of High patients identified at 2 months remained High long-term, Brier score = 0.06). Multivariate analysis revealed that High patients determined at 2 months (n = 499) had a significantly higher risk of allograft loss (cause-specific hazard ratio [CS-HR] = 2.00, 95% confidence interval [CI] = 1.48–2.69) and allograft rejection (CS-HR = 1.71, 95% CI = 1.15–2.54) than Low patients after adjustment for confounding factors. Moreover, allograft function was lower in High patients (46.7 vs. 52.9 ml/min, at 3 years, P < 0.0001) with a higher proportion of chronic vascular lesions at 1 year. Conclusion: C0/D is a simple and pragmatic tool capable of identifying patients at risk of rejection and allograft failure as early as the second month posttransplantation.http://www.sciencedirect.com/science/article/pii/S2468024925001032allograft survivalkidney transplantationtacrolimus toxicity |
| spellingShingle | Christophe Masset Marine Lorent Clarisse Kerleau Claire Garandeau Aurélie Houzet Simon Ville Diego Cantarovich Gilles Blancho Magali Giral Jacques Dantal Gilles Blancho Julien Branchereau Diego Cantarovich Agnès Chapelet Jacques Dantal Florent Delbos Clément Deltombe Lucile Figueres Charles Ronsin Thibault Letellier Clémence Petit Claire Garandeau Magali Giral Caroline Gourraud-Vercel Laurent Nicolet Christine Kandel-Aznar Ismaël Chelghaf Clarisse Kerleau Christophe Masset Aurélie Meurette Karine Renaudin Simon Ville Alexandre Walencik Early Determination of Tacrolimus Concentration–Dose Ratio Identifies Risk of Allograft Loss in Kidney Transplantation Kidney International Reports allograft survival kidney transplantation tacrolimus toxicity |
| title | Early Determination of Tacrolimus Concentration–Dose Ratio Identifies Risk of Allograft Loss in Kidney Transplantation |
| title_full | Early Determination of Tacrolimus Concentration–Dose Ratio Identifies Risk of Allograft Loss in Kidney Transplantation |
| title_fullStr | Early Determination of Tacrolimus Concentration–Dose Ratio Identifies Risk of Allograft Loss in Kidney Transplantation |
| title_full_unstemmed | Early Determination of Tacrolimus Concentration–Dose Ratio Identifies Risk of Allograft Loss in Kidney Transplantation |
| title_short | Early Determination of Tacrolimus Concentration–Dose Ratio Identifies Risk of Allograft Loss in Kidney Transplantation |
| title_sort | early determination of tacrolimus concentration dose ratio identifies risk of allograft loss in kidney transplantation |
| topic | allograft survival kidney transplantation tacrolimus toxicity |
| url | http://www.sciencedirect.com/science/article/pii/S2468024925001032 |
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