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Cardiovascular (CV) pathologies are the leading cause of death in kidney transplant patients.Arterial stiffness is a prognostic factor for CV mortality in kidney transplantation. Despite a reduced CV risk in transplant kidney patients in comparison to patients in dialysis, CV mortality among kidney transplant patients is much higher than the general population.
After renal transplantation, the cardiac and vascular anomalies observed in chronic end-stage renal disease are partially improved because of restored normal kidney function and withdrawal from dialysis.
However, patients are exposed to immunosuppressive drugs, in particular calcineurin inhibitors, which can be associated with vascular toxicity, either directly or by promoting the appearance of hypertension, diabetes, or dyslipidemia.The pathophysiology of arterial stiffness in kidney transplantation is complex and multifactorial.
Calcineurin inhibitors are likely to play an important role in the persistence of increased arterial stiffness in transplant patients in whom renal function has been restored. Indeed, the discontinuation of anti-calcineurins in favour of other molecules .is associated with a decrease of arterial stiffness.
Preclinical work has shown that the vascular toxicity of cyclosporine is mediated by activation of the mineralocorticoid receptor in smooth muscle cells. The involvement of the mineralocorticoid receptor in the onset of arterial stiffness is also well demonstrated in non-transplanted subjects.
Blocking the mineralocorticoid receptor in patients under cyclosporine may reduce their arterial stiffness and in and consequently improve their CV prognosis.
Studies have show a good safety in kidney transplant patients. This pilot study proposes to examine, for the first time, the impact of treatment with a mineralocorticoid receptor antagonist on the evolution of arterial stiffness in renal transplant patients on calcineurin inhibitors.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Eplerenone group A (cross over design) | Active Comparator | Patient will receive eplerenone 50mg/day taken orally for 6 months, followed by a 8 to 10 weeks wash-out period, then a 6-month period without eplerenone, until the end of the study. |
|
| Eplerenone group B (cross over design) | Active Comparator | Eplerenone-free for 6 months, followed by a 8 to 10 weeks wash-out period, then a 6-month period in which patients will receive eplerenone 50 mg/day as a single dose taken orally. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Eplerenone 50mg/day (cross over design) | Drug | Eplerenone 50mg/day for 6 months followed |
|
| Measure | Description | Time Frame |
|---|---|---|
| Evolution of pulse wave velocity (PWV in m/s) adjusted to the blood pressure | After 6 months of treatment with eplerenone |
| Measure | Description | Time Frame |
|---|---|---|
| Evolution of Central Systolic Blood Pressure (CSPc) | After 6 months of treatment with eplerenone | |
| Evolution of central Diastolic Blood Pressure (CDAb) | After 6 months of treatment with eplerenone |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sophie GIRERD, MD-phD | Contact | (0) 3 83 15 73 22 | +33 | s.girerd@chru-nancy.fr |
| Nicolas GIRERD, MD-PhD | Contact | (0) 3 83 15 73 22 | +33 | n.girerd@chru-nancy.fr |
| Name | Affiliation | Role |
|---|---|---|
| Nicolas GIRERD, MD-Phd | Central Hospital, Nancy, France | Study Chair |
| Sophie GIRERD, MD-PhD | Central Hospital, Nancy, France | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHRU de Nancy | Recruiting | Vandœuvre-lès-Nancy | 54500 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41204172 | Derived | Simon A, Girerd N, Jaisser F, Bozec E, Lepage X, Merckle L, Rossignol P, Frimat L, Girerd S. EVATRAN (The Effect of Eplerenone on the Evolution of Vasculopathy in Renal Transplant Patients): study protocol for a cross-over randomized controlled trial. Trials. 2025 Nov 7;26(1):479. doi: 10.1186/s13063-025-09187-w. | |
| 39082471 | Derived |
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| Period without eplerenone (cross over design) | Other | 6-month period without eplerenone |
|
| Evolution of Central Pulsed Pressure (CPp) | After 6 months of treatment with eplerenone |
| Evolution of Augmentation index (Aix in %) | After 6 months of treatment with eplerenone |
| Evolution peripheral systolic blood pressure (PASp in mmHg) | After 6 months of treatment with eplerenone |
| Evolution of peripheral diastolic blood pressure (PADp in mmHg) | After 6 months of treatment with eplerenone |
| Evolution of peripheral pulse pressure (PPp in mmHg) | After 6 months of treatment with eplerenone |
| Evolution of Intima-media thickness (in mm) | After 6 months of treatment with eplerenone |
| Evolution of left ventricular mass (LVM in g/m2) | After 6 months of treatment with eplerenone |
| Evolution of biological markers of oxidative stress (plasma Isoprostane) | After 6 months of treatment with eplerenone |
| Evolution of biological markers of oxidative stress (Malondialdehyde) | After 6 months of treatment with eplerenone |
| Evolution of Biological markers of endothelial dysfunction (endothelin) | After 6 months of treatment with eplerenone |
| Evolution of biological markers of endothelial dysfunction (soluble endothelium selectin (sE-selectin)) | After 6 months of treatment with eplerenone |
| Evolution of biological markers of endothelial dysfunction (von Willebrand factor) | After 6 months of treatment with eplerenone |
| Evolution of graft function | measured by creatinine (in micromol/L) with estimation of glomerular filtration rate (eGFR in mL/min/1.73m2 ) according to the CKD-EPI formula. | After 6 months of treatment with eplerenone |
| Evolution of proteinuria | measured by the ratio proteinuria/creatinuria (in mg/g) | After 6 months of treatment with eplerenone |
| Percentage of patients with DFG ≥ 90, 60-89, 45-59, 30-44, 15-29 <15ml/min/1,73m2 | After 6 months of treatment with eplerenone |
| Percentage of patient with ratio proteinuria/creatinuria (en mg/g) <500 ; 500-1000, 1000-2000, 2000-3000, >3000 | After 6 months of treatment with eplerenone |
| hyperkalemia occurence ≥ 5.5 mmol/L | during 6 month of treatment with eplerenone |
| Number of hyperkalemia | number of hyperkalemias during hyperkalemia follow-up between 5 - 5.49; 5.5 - 6; >6mmol/L | during 6 month of treatment with eplerenone |
| increase of creatinine of more than 50% | Evaluation of risk of acute renal failure defined as an increase in creatinine of more than 50% | during 6 month of treatment with eplerenone |
| Natale P, Mooi PK, Palmer SC, Cross NB, Cooper TE, Webster AC, Masson P, Craig JC, Strippoli GF. Antihypertensive treatment for kidney transplant recipients. Cochrane Database Syst Rev. 2024 Jul 31;7(7):CD003598. doi: 10.1002/14651858.CD003598.pub3. |
| ID | Term |
|---|---|
| D000077545 | Eplerenone |
| D018592 | Cross-Over Studies |
| ID | Term |
|---|---|
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D015340 | Epidemiologic Research Design |
| D004812 | Epidemiologic Methods |
| D008919 | Investigative Techniques |
| D017531 | Health Care Evaluation Mechanisms |
| D011787 | Quality of Health Care |
| D017530 | Health Care Quality, Access, and Evaluation |
| D011634 | Public Health |
| D004778 | Environment and Public Health |
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