Kidney Transplant Recipients
Conditions
Brief summary
Endothelial lesions within the transplanted kidney are a major determinant of chronic allograft nephropathy. Epoxyeicosatrienoic acids (EETs) are endothelium-derived hyperpolarizing factors with anti-inflammatory, antiproliferative and vasodilator properties. The main goal of the investigators' study is to evaluate whether genetic polymorphisms of specific enzymes responsible for the bioavailability of EETs are associated with post-transplant kidney function. To this end, 80 kidney transplant recipients will be included. Prespecified genetic polymorphisms of CYP 2J2, CYP 2C8, CYP 2C9, CYP 2C9, CYP 2C19 and EPHX2 will be determined. Kidney function will be recorded 3, 6, 12 and 36 months after transplantation. Flow-mediated dilatation, EETs and circulating biomarkers of endothelial function will be measured in the radial artery. The expected results of this study to provide preliminary evidence supporting a beneficial role of an increase in the bioavailability of EETs in kidney transplant recipients.
Interventions
PROCEDUREBlood sampling
Blood sampling is done for Kidney transplant recipients for evaluation of the polymorphisms and EETs dosage
PROCEDUREflow-mediated distal stimulation of the forearm radial artery by cutaneous heating
Flow-mediated distal stimulation of the forearm radial artery by cutaneous heating for Kidney transplant recipients
Sponsors
University Hospital, Rouen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patient aged 18 to 75 yo * Caucasian (because of different CYP epoxygenase polymorphisms) * First kidney transplantation performed in Rouen University Hospital after 2000, and at least 12 months before inclusion * Patient having read, understood and approved the informed consent * Efficient contraception in child-bearing aged women * Regular health insurance
Exclusion criteria
* Primary non-function, or allograft loss before 1 year * Previous kidney transplantation * History of psychiatric, psychologic or sensorial disorder preventing the patient from correctly understanding the protocol * History of bilateral arm or forearm arteriovenous fistula * Counter-indication to trinitrin * Insufficient understanding of written or spoken French language * Liberty-deprived patient * Pregnancy or absence of contraception in child-bearing aged women * Patient enrolled in another research protocol within 2 weeks before inclusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference between patients with the EPHX2 Lys55Arg polymorphism and patients without in estimated Glomerular Filtration Rate (eGFR) | 12 Months after transplantation | eGFR Scores range from 0 \[kidney failure\] to \>90 \[normal function\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference between patients with the EPHX2 Lys55Arg polymorphism and patients without in estimated Glomerular Filtration Rate (eGFR) | 3 Months after transplantation | eGFR Scores range from 0 \[kidney failure\] to \>90 \[normal function\] |
| Difference between patients with specified polymorphisms and patients without in estimated Glomerular Filtration Rate (eGFR) | 3 Months after transplantation | eGFR Scores range from 0 \[kidney failure\] to \>90 \[normal function\] |
| Difference between blood EETs concentration at baseline and after distal cutaneous heating for patients with the specified polymorphisms. | Day 1 | EEts plasma concentration is measured using liquid chromatography coupled to tandem mass spectrometry before and after distal cutaneous heating. Unit is ng per mL |
| Difference between blood EETs concentration at baseline and after distal cutaneous heating for patients without the specified polymorphisms. | Day 1 | EEts plasma concentration is measured using liquid chromatography coupled to tandem mass spectrometry before and after distal cutaneous heating. Unit is ng per mL |
| Difference between variation of diameter of the forearm radial artery after distal cutaneous heating for patients with the specified polymorphisms. | Day 1 | Variation of diameter of the radial artery is measured in millimeter. |
| Difference between variation of diameter of the forearm radial artery after distal cutaneous heating for patients without the specified polymorphisms. | Day 1 | Variation of diameter of the radial artery is measured in millimeter. |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORDominique GUERROT, Pr
University Hospital, Rouen
Outcome results
None listed