Kidney transplant recipients usually lose their graft by rejection or by immunosuppressive drugs toxicity. In kidney transplantation, calcineurin-inhibitors (including cyclosporine A) are widely used. Their renal toxicity could be divided between an acute toxicity (toxic arteriolopathy and toxic tubulopathy) and a chronic toxicity (hyaline arteriolopathy, interstitial fibrosis, tubular atrophy and glomerulosclerosis). Several animal models have shown the implication of the mineralocorticoid receptor (MR) activation in those toxic phenomenons. The use of a mineralocorticoid receptor antagonist is useful regarding to the renal function and kidney histological damages.

Several antagonists are available in France but none is indicated in kidney transplantation. Eplerenone appears to be the most selective molecule of the mineralocorticoid receptor and to have less adverse anti-androgenic effects than others molecules. Its principal adverse events are hyperkalemia and orthostatic hypotension. Mineralocorticoid receptor antagonists, especially eplerenone, could be very useful in the prevention of the nephrotoxicity induced by calcineurin-inhibitors.

Classically, eplerenone is contra-indicated in patients presenting with an impaired renal function, determined by a creatinine clearance under 50mL/min. Moreover, in France, a warning is especially notified for the association with cyclosporine A due to the fact that no study have been done in this context.

The investigators study first the safety of the use of eplerenone in association with cyclosporine A in kidney transplant recipients. Then, if it is safe, the investigators will study its efficiency in a large randomized controlled trial.

Inclusion Criteria:

All the patients that will be included in this trial have to fulfil all the following conditions:

• more than 18-years old at the date of inclusion
• a full legal capacity
• belonging to a health care system
• give their written consent
• a functional kidney allograft for at least 1 year from the date of inclusion
• be under cyclosporine A-treatment
• impaired renal function estimated by the MDRD formula between 30 to 50mL/min/1.73m²

Exclusion Criteria:

All the patients that will be included in this trial have to fulfil no one of the following conditions:

• serum potassium higher than or equal to 5mmol/L at the date of inclusion
• one or more history of severe hyperkalemia (serum potassium higher than or equal to 6mmol/L) whatever the reason
• currently under potassium exchange resin treatment like KAYEXALATE®
• an acute rejection of the graft within the 6 months before the date of inclusion
• an ongoing pregnancy or a lack of effective contraception during all the study
• an uncontrolled high arterial blood pressure
• an orthostatic hypotension
• a systolic arterial blood pressure under or equal to 110mmHg
• a heart failure within the past 3 months before the date of inclusion or a chronic heart failure (stages III or IV of the NYHA classification)
• a severe hepatic failure (stage C of the Child-Pugh classification)
• an allergy to one or more of the components of the speciality eplerenone - INSPRA®
• an ongoing treatment with spironolactone - ALDACTONE® or eplerenone - INSPRA®
• a contra-indicated association whose treatment could not be suspended during the study: potassium sparing diuretics, potassium salts, enzymatic inhibitors of CYP3A4 (like itraconazole, ketoconazole, ritonavir, nelfinavir, clarithromycine, telithromycine, nefazodone)
• a malabsorption syndrome, an abnormality of galactose metabolism or a deficiency in galactase
• an ongoing treatment with nonsteroidal anti-inflammatory or with lithium or another nephrotoxic agent
• an ongoing treatment with a double-blockade of the Renin-Angiotensin-Aldosterone System by the association ACE-I (Angiotensin-Converting Enzyme Inhibitor) and ARB (Angiotensin Receptor Blocker)