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The Effect of Eplerenone on the Evolution of Vasculopathy in Renal Transplant Patients.

Sponsor: Central Hospital, Nancy, France

Summary

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.

Official title: A Randomized Crossover Clinical Trial Regarding the Blockage of the Mineralocorticoid Receptor Using Eplerenone on the Evolution of Arterial Stiffness in Kidney Patients One Year After Transplant

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