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

NCT ID: NCT04963673

Last Updated: 2023-09-14

Basic Information

• Recruitment Status: WITHDRAWN
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-07-06
• Study Completion Date: 2023-09-12

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.

Conditions

Kidney Transplant; Immunosuppression; Uremic; Toxemia

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

DFG> 40 ml / min

Kidney transplant population followed at CHU Amiens (group 1 ⇾ DFG\> 40 ml / min).

calcineurin inhibitor dosage

Intervention Type: OTHER

The dosage of calcineurin inhibitors will be done as usual by the toxicology pharmacology laboratory of the CHU Amiens-Picardie. If the patient does not object, the determination of protein-bound uremic toxins from the rest of the collected blood tube will be performed using high performance liquid chromatography.

DFG < 40 ml / min

Kidney transplant population followed at CHU Amiens (group 2 ⇾ DFG \< 40 ml / min).

calcineurin inhibitor dosage

Intervention Type: OTHER

The dosage of calcineurin inhibitors will be done as usual by the toxicology pharmacology laboratory of the CHU Amiens-Picardie. If the patient does not object, the determination of protein-bound uremic toxins from the rest of the collected blood tube will be performed using high performance liquid chromatography.

Interventions

calcineurin inhibitor dosage

The dosage of calcineurin inhibitors will be done as usual by the toxicology pharmacology laboratory of the CHU Amiens-Picardie. If the patient does not object, the determination of protein-bound uremic toxins from the rest of the collected blood tube will be performed using high performance liquid chromatography.

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire, Amiens

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Youssef Bennis, MD

Role: PRINCIPAL_INVESTIGATOR

CHU Amiens

Sandra Bodeau, MD

Role: PRINCIPAL_INVESTIGATOR

CHU Amiens

Locations

CHU Amiens

Amiens, , France

Countries

France

Other Identifiers

PI2019_843_0060

Identifier Type: -

Identifier Source: org_study_id