Evaluation of Interaction Between Immunosuppressive Drugs and Protein-bound Uremic Toxins in Renal Transplant Patients

Overview

The majority of studies conducted on uremic toxins involve patients before end stage renal failure or dialysis patients. Only a few studies have focused on transplant patients. In addition, the relationship between serum concentrations of uremic toxins and immunosuppressive drug concentrations has never been studied to date. The investigator research hypothesis is that, due to the strong plasma protein binding of calcineurin inhibitors, an interaction with protein-bound uremic toxins could alter drug concentrations that explain difficulties in reaching therapeutic targets.

In France, the national prevalence of end-stage kidney disease (including dialysis and renal transplantation) is 1,232 per million inhabitants. As in all transplants, renal transplantation needs immunosuppressive therapy. This treatment may be difficult to adjust in some patients. However, achieving the therapeutic target is essential to have an efficiency synonymous with graft survival and better tolerance to the drug. The immunosuppressive class drug of interest in the present project is the class of calcineurin inhibitors (tacrolimus and ciclosporin) that are widely used in both initial and maintenance immunosuppression. These drugs have the pharmacological specificities to be highly bound to plasma proteins and requiring pharmacological therapeutic monitoring. With the progression of chronic kidney disease, many molecules accumulate as a result of decreased kidney excretion capacity, such as compounds called uremic toxins. The investigators research is part of the European network for the study of these toxins (Eutox group) and has largely contributed to the better knowledge of these toxins. In particular, they are defined by their dose-dependent deleterious effects. These molecules are classified, according to their molecular weight, into small molecules, medium molecules and molecules strongly bound to plasma proteins (p-cresyl sulphate \[pCS\], indoxyl sulphate \[IS\] and indol acetic acid \[IAA\]). This last group of protein will be evaluated in this project. The majority of studies conducted on uremic toxins involve patients before end stage renal failure or dialysis patients. Only a few studies have focused on transplant patients. In addition, the relationship between serum concentrations of uremic toxins and immunosuppressive drug concentrations has never been studied to date. the investigator research hypothesis is that, due to the strong plasma protein binding of calcineurin inhibitors, an interaction with protein-bound uremic toxins could alter drug concentrations that explain difficulties in reaching therapeutic targets.

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