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

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.

Study Overview

• Status: Completed
• Conditions: Kidney Transplant Recipients
• Intervention / Treatment: Procedure: Blood sampling; Procedure: flow-mediated distal stimulation of the forearm radial artery by cutaneous heating

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Rouen, France, 76031
    • Rouen University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Kidney transplant recipients; blood sampling is done for determination of EPHX Lys55Arg and other polymorphisms status in Kidney transplant recipients. flow-mediated distal stimulation of the forearm radial artery by cutaneous heating is assessed for evaluation of EEts level in Kidney transplant recipients.	Procedure: Blood sampling; Blood sampling is done for Kidney transplant recipients for evaluation of the polymorphisms and EETs dosage; Procedure: flow-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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference between patients with the EPHX2 Lys55Arg polymorphism and patients without in estimated Glomerular Filtration Rate (eGFR)	eGFR Scores range from 0 [kidney failure] to >90 [normal function]	12 Months after transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference between patients with the EPHX2 Lys55Arg polymorphism and patients without in estimated Glomerular Filtration Rate (eGFR)	eGFR Scores range from 0 [kidney failure] to >90 [normal function]	3 Months after transplantation
Difference between patients with the EPHX2 Lys55Arg polymorphism and patients without in estimated Glomerular Filtration Rate (eGFR)	eGFR Scores range from 0 [kidney failure] to >90 [normal function]	6 Months after transplantation
Difference between patients with the EPHX2 Lys55Arg polymorphism and patients without in estimated Glomerular Filtration Rate (eGFR)	eGFR Scores range from 0 [kidney failure] to >90 [normal function]	36 Months after transplantation
Difference between patients with specified polymorphisms and patients without in estimated Glomerular Filtration Rate (eGFR)	eGFR Scores range from 0 [kidney failure] to >90 [normal function]	3 Months after transplantation
Difference between patients with specified polymorphisms and patients without in estimated Glomerular Filtration Rate (eGFR)	eGFR Scores range from 0 [kidney failure] to >90 [normal function]	6 Months after transplantation
Difference between patients with specified polymorphisms and patients without in estimated Glomerular Filtration Rate (eGFR)	eGFR Scores range from 0 [kidney failure] to >90 [normal function]	12 Months after transplantation
Difference between patients with specified polymorphisms and patients without in estimated Glomerular Filtration Rate (eGFR)	eGFR Scores range from 0 [kidney failure] to >90 [normal function]	36 Months after transplantation
Difference between blood EETs concentration at baseline and after distal cutaneous heating for patients with the specified polymorphisms.	EEts plasma concentration is measured using liquid chromatography coupled to tandem mass spectrometry before and after distal cutaneous heating. Unit is ng per mL	Day 1
Difference between blood EETs concentration at baseline and after distal cutaneous heating for patients without the specified polymorphisms.	EEts plasma concentration is measured using liquid chromatography coupled to tandem mass spectrometry before and after distal cutaneous heating. Unit is ng per mL	Day 1
Difference between variation of diameter of the forearm radial artery after distal cutaneous heating for patients with the specified polymorphisms.	Variation of diameter of the radial artery is measured in millimeter.	Day 1
Difference between variation of diameter of the forearm radial artery after distal cutaneous heating for patients without the specified polymorphisms.	Variation of diameter of the radial artery is measured in millimeter.	Day 1

Collaborators and Investigators

• Sponsor: University Hospital, Rouen
• Investigators: Principal Investigator: Dominique GUERROT, Pr, University Hospital, Rouen

Publications and helpful links

General Publications

• Duflot T, Laurent C, Soudey A, Fonrose X, Hamzaoui M, Iacob M, Bertrand D, Favre J, Etienne I, Roche C, Coquerel D, Le Besnerais M, Louhichi S, Tarlet T, Li D, Brunel V, Morisseau C, Richard V, Joannides R, Stanke-Labesque F, Lamoureux F, Guerrot D, Bellien J. Preservation of epoxyeicosatrienoic acid bioavailability prevents renal allograft dysfunction and cardiovascular alterations in kidney transplant recipients. Sci Rep. 2021 Feb 12;11(1):3739. doi: 10.1038/s41598-021-83274-1.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: September 17, 2015
• First Submitted That Met QC Criteria: September 17, 2015
• First Posted (Estimated): September 21, 2015

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: 2013/150/HP