Role of Epoxyeicosatrienoic Acids in Chronic Allograft Nephropathy - The TRANSPLANT-EETs Study

Role of Epoxyeicosatrienoic Acids in Chronic Allograft Nephropathy

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.

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