The Influence of Tacrolimus Exposure and Metabolism on the Outcomes of Kidney Transplants

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dc.contributor.authorMaslauskiene, Rima
dc.contributor.authorVaiciuniene, Ruta
dc.contributor.authorRadzeviciene, Aurelija
dc.contributor.authorTretjakovs, Pēteris
dc.contributor.authorGersone, Gita
dc.contributor.authorStankevicius, Edgaras
dc.contributor.authorBumblyte, Inga Arune
dc.contributor.institutionDepartment of Human Physiology and Biochemistry
dc.date.accessioned2024-06-21T11:55:01Z
dc.date.available2024-06-21T11:55:01Z
dc.date.issued2024-05
dc.descriptionPublisher Copyright: © 2024 by the authors.
dc.description.abstractTacrolimus (TAC) has a narrow therapeutic window and patient-specific pharmacokinetic variability. In our study, we analyzed the association between TAC exposure, metabolism, and kidney graft outcomes (function, rejection, and histological lesions). TAC trough (C0), coefficient of variation (TAC CV), concentration/dose ratio (C/D), and biomarkers related to kidney injury molecule-1 (KIM-1) and neutrophil gelatinase lipocalin (NGAL) were analyzed. We examined 174 patients who were subjected to a triple immunosuppressive regimen and underwent kidney transplantation between 2017 and 2022. Surveillance biopsies were performed at the time of kidney implantation and at three and twelve months after transplantation. We classified patients based on their Tac C/D ratios, classifying them as fast (C/D ratio < 1.05 ng/mL × 1/mg) or slow (C/D ratio ≥ 1.05 ng/mL × 1/mg) metabolizers. TAC exposure/metabolism did not significantly correlate with interstitial fibrosis/tubular atrophy (IF/TA) progression during the first year after kidney transplantation. TAC CV third tertile was associated with a higher chronicity score at one-year biopsy. TAC C/D ratio at three months and Tac C0 at six months were associated with rejection during the first year after transplantation. A fast TAC metabolism at six months was associated with reduced kidney graft function one year (OR: 2.141, 95% CI: 1.044–4.389, p = 0.038) and two years after transplantation (OR: 4.654, 95% CI: 1.197–18.097, p = 0.026), and TAC CV was associated with reduced eGFR at three years. uNGAL correlated with IF/TA and chronicity scores at three months and negatively correlated with TAC C0 and C/D at three months and one year. Conclusion: Calculating the C/D ratio at three and six months after transplantation may help to identify patients at risk of suffering acute rejection and deterioration of graft function.en
dc.description.statusPeer reviewed
dc.format.extent14
dc.format.extent845757
dc.identifier.citationMaslauskiene, R, Vaiciuniene, R, Radzeviciene, A, Tretjakovs, P, Gersone, G, Stankevicius, E & Bumblyte, I A 2024, 'The Influence of Tacrolimus Exposure and Metabolism on the Outcomes of Kidney Transplants', Biomedicines , vol. 12, no. 5, 1125. https://doi.org/10.3390/biomedicines12051125
dc.identifier.doi10.3390/biomedicines12051125
dc.identifier.issn2227-9059
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/15531
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85194060895&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofBiomedicines
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectC/D ratio
dc.subjectkidney injury molecule-1
dc.subjectkidney transplantation
dc.subjectneutrophil gelatinase-associated lipocalin
dc.subjecttacrolimus coefficient of variation
dc.subjecttacrolimus monitoring
dc.subject3.1 Basic medicine
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.subjectMedicine (miscellaneous)
dc.subjectGeneral Biochemistry,Genetics and Molecular Biology
dc.titleThe Influence of Tacrolimus Exposure and Metabolism on the Outcomes of Kidney Transplantsen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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