Clinical trial NCT04963673: Evaluation of Interaction Between Immunosuppressive Drugs and Protein-bound Uremic Toxins in Renal Transplant Patients
Official title: Evaluation of Interaction Between Immunosuppressive Drugs and Protein-bound Uremic Toxins in Renal Transplant Patients
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Kidney Transplant
Immunosuppression
Uremic; Toxemia
Keywords: Kidney Transplant
Immunosuppression
Uremic; Toxemia
Lead sponsor: Centre Hospitalier Universitaire, Amiens
Sponsor class: OTHER
First posted: 2021-07-15
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Kidney transplant population followed at CHU Amiens (group 1 ⇾ DFG\> 40 ml / min, group 2 ⇾ DFG \< 40 ml / min).

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* renal transplant patient followed at the University Hospital of Amiens and transplanted for over a year
* patient treated with a calcineurin inhibitor
* patient having a blood test for evaluation of calcineurin inhibitor concentrations by the toxicology pharmacology laboratory of the Amiens-Picardie University Hospital,
* patient affiliated with social security.

Exclusion Criteria:

* patient in phase of acute rejection of the graft,
* patient having opposed his participation,
* patient under guardianship or curatorship or deprived of public right

Primary outcomes:
measure: plasma tacrolimus concentration without plasma uremic toxin adjustment
timeFrame: at day 0
measure: plasma tacrolimus concentration with plasma uremic toxin adjustment
timeFrame: at day 0
Secondary outcomes:
measure: plasma ciclosporin concentration without plasma uremic toxin adjustment
timeFrame: at day 0
measure: plasma ciclosporin concentration with plasma uremic toxin adjustment
timeFrame: at day 0
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens
Study officials:
affiliation: CHU Amiens
name: Youssef Bennis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Amiens
name: Sandra Bodeau, MD
role: PRINCIPAL_INVESTIGATOR
References: