The impact of the tacrolimus concentration/dose ratio on kidney function in heart transplant recipients
Summary
Background. 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.