Overview

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.

Eligibility

Inclusion Criteria:

• Men or women ≥ 50 years of age;
• Patient who had a kidney transplant at least one year prior to inclusion;
• Patient on cyclosporine;
• Patient whose clinical-biological state has been stable for at least 3 months: no change in treatment with an impact on blood pressure (excluding immunosuppressive drug) for 3 months, no acute rejection diagnosed within 3 months;
• Patient with a glomerular filtration rate estimated according to the formula CKD-EPI ≥30mL/min/1.73m2;
• Patient with a peripheral PAS≥110mmHg, irrespective of the presence or not of an antihypertensive therapy (including ACE inhibitors or sartan) ;
• Patient with signed informed consent;
• Patient affiliated with or beneficiary of a social security system.

Exclusion Criteria:

• Patient with documented kalemia ≥ 5mmol/L in the last 15 days;
• Patient undergoing mineralocorticoid receptor antagonism or with a formal indication to receive this treatment;
• Bicarbonate blood level <20mmol/L with or without documented supplementation in the last 15 days.
• Indication for a combination of ACE inhibitor and sartan (each of which is authorized separately);
• Patient under another potassium sparing diuretics;
• Patient under digoxine;
• Sodium polystyrene sulfonate contraindication;
• Known hypersensitivity or allergy to eplerenone and its excipients;
• Patient with severe hepatic impairment (Child-Pugh Class C);
• Patient under CYP3A4 inhibitor;
• know intolerance to Galactose, a Lapp lactase deficiency or galactose malabsorption syndrome;
• Patient participating in other interventional research;
• Woman with a desire of pregnancy within 15 months;
• Woman of childbearing age without effective contraception;
• Persons referred to in Articles L. 1121-5, L. 1121-7 and L1121-8 of the Public Health Code :
• Pregnant women, parturient women or nursing mothers ;
• Adult person subject to a legal protection measure (guardianship, curator, judicial safeguard);
• Adults person who is unable to give consent and who is not subject to a legal protection measure;
• Persons deprived of their liberty by a judicial or administrative decision;
• Persons subject to psychiatric care pursuant to articles L. 3212-1 and L. 3213-1.