A large array of immunosuppressive agents is available for prevention of rejection in recipients of a renal allograft. However, almost every renal transplant patient receives a similar combination of immunosuppressive drugs, which includes induction therapy, a calcineurin inhibitor, predominantly tacrolimus, MMF and frequently steroids. As most acute rejections occur in the first 6 months after renal transplantation, this universal approach can be defended for this period in which the focus should be on maximal effectiveness of the immunosuppressive therapy (42). However, the maintenance regimen that is used beyond the first 6-12 months after transplantation is frequently also a fixed combination of immunosuppressive drugs. This fixed combination usually consists of tacrolimus in combination with MMF and/or steroids depending on the transplant center and irrespective
of the risk of rejection, adverse effects, degree of adherence, original kidney disease, and co-morbidity. A fixed regimen in all patients does not take into account the obvious differences between patients. In a personalized or tailor made approach, the different factors are balanced per individual to optimize the immunosuppressive therapy. We propose to apply this approach beyond the first 6-12 months post transplantation. It might improve the efficacy, reduce the side effects and increase adherence resulting in better long-term outcomes and a better quality of life.
Immunosuppressive drug trials with the treatment guided by pharmacogenetic traits and TDM to individualize immunosuppressive therapy after renal transplantation have been conducted (43-45). However, studies in which the choice for an immunosuppressive regimen in a single patient is explicitly based on a combination of pharmacogenetics, risk of rejection, adverse effects, degree of adherence, original kidney disease, comorbidity, and preference of the patient are lacking thus far. We evaluated the available evidence for choosing a specific immunosuppressive strategy in an individual with a specified set of clinical characteristics. Based on the available data, we developed a preliminary version of a scoring system that can aid in choosing the most appropriate maintenance regimen for a given patient. Our ultimate goal is to perform a clinical trial in which tailor-made immunosuppression according to this scoring system is compared with ‘standard’ therapy. It is a challenge to define the most appropriate endpoints for such a trial, trying to find an optimal balance between classical endpoints, like graft function and survival, and patient reported outcome measures referring to the quality of life. Moreover, motivating renal transplant patients to change an immunosuppressive regimen to which they are accustomed can be a difficult job. Nevertheless, we feel that such studies will be worthwhile to improve long-term outcome of renal transplantation.
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