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dc.rights.licenseCC-BY-NC-ND
dc.contributor.advisorBinkhorst, L.
dc.contributor.authorSeijkens, Boris
dc.date.accessioned2023-08-25T00:00:56Z
dc.date.available2023-08-25T00:00:56Z
dc.date.issued2023
dc.identifier.urihttps://studenttheses.uu.nl/handle/20.500.12932/44778
dc.description.abstractBackground. Tacrolimus is the backbone of immunosuppression after heart transplantation (HTx). Although being highly effective, nephrotoxicity is a frequent complication. Tacrolimus-induced nephrotoxicity is considered to be an important cause of kidney disease after HTx. The tacrolimus concentration/dose ratio (C0/D-ratio) is a reflection of the metabolic rate of a patient for tacrolimus. Recent studies demonstrated a relationship between the tacrolimus C0/D-ratio and adverse clinical outcomes, including nephrotoxicity in solid organ transplantation, mainly kidney transplants. We investigated the impact of the tacrolimus C0/D-ratio on kidney function, assessed with the estimated glomerular filtration rate (eGFR), in HTx-recipients. Methods. This was a retrospective study in HTx-recipients who were treated with tacrolimus as initial immunosuppression for at least six months after transplantation. Data on C0/D-ratio and eGFR were collected at three and six months, and at one, three and five years post-HTx. Patients were categorized into four tacrolimus metabolism groups based on the median C0/D-ratio of the population. A linear mixed model was performed to assess the correlation between time-varying C0/D-ratio and time-varying eGFR. Additionally, multivariate analyses were carried out to assess the relationship between the C0/D-ratio and eGFR at the different time points. Furthermore, a survival analysis between the four groups was carried out. Results. Two-hundred and nine HTx-recipients were included. No relationship between time-varying logarithmically-transformed (Log) C0/D-ratio and time-varying eGFR was found in the linear mixed model (p = 0.71). However, the Log tacrolimus C0/D-ratio was positively associated with eGFR at three months, six months and one year after HTx in multivariate analyses (p = 0.02, p<0.001, and p = 0.009, respectively). Finally, no noticeable difference in survival rate was found between the four groups (p = 0.25). Conclusions. The Log tacrolimus C0/D-ratio was positively associated with kidney function up to one year after HTx in multivariate analyses, but no association was found between time-varying Log C0/D-ratio and eGFR in a linear mixed model. So, the question remains whether a real association is present.
dc.description.sponsorshipUtrecht University
dc.language.isoEN
dc.subjectDe tacrolimus concentratie/dosis ratio (C/D-ratio) is een reflectie van de metabolische capaciteit van een persoon voor tacrolimus. Eerdere studies hebben een verband aangetoond tussen de tacrolimus C/D-ratio en negatieve uitkomsten na orgaantransplantatie, met name in niertransplantatiepatiënten. In deze studie is de associatie tussen de tacrolimus C/D-ratio en nierfunctie in harttransplantatiepatiënten onderzocht.
dc.titleThe impact of the tacrolimus concentration/dose ratio on kidney function in heart transplant recipients
dc.type.contentMaster Thesis
dc.rights.accessrightsOpen Access
dc.subject.keywordstacrolimus, heart transplantation, concentration/dose ratio, kidney function
dc.subject.courseuuFarmacie
dc.thesis.id22660


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