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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Kidney transplant recipients | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Blood sampling | Procedure | Blood sampling is done for Kidney transplant recipients for evaluation of the polymorphisms and EETs dosage |
|
| 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 |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dominique GUERROT, Pr | University Hospital, Rouen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rouen University Hospital | Rouen | 76031 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33580125 | Result | 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. |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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| flow-mediated distal stimulation of the forearm radial artery by cutaneous heating | Procedure | Flow-mediated distal stimulation of the forearm radial artery by cutaneous heating for Kidney transplant recipients |
|
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 |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |