title: Immunosuppressant regimen based on sirolimus decreases aortic stiffness in renal transplant recipients in comparison to cyclosporine.
abstract: Whether or not a cyclosporine A (CsA)-free immunosuppressant regimen based on sirolimus (SRL) prevents aortic stiffening and improves central hemodynamics in renal recipients remains unknown. Forty-four patients (48 ± 2 years) enrolled in the CONCEPT trial were randomized at week 12 (W12) to continue CsA or switch to SRL, both associated with mycophenolate mofetil. Carotid systolic blood pressure (cSBP), pulse pressure (cPP), central pressure wave reflection (augmentation index, AIx) and carotid-to-femoral pulse-wave velocity (PWV: aortic stiffness) were blindly assessed at W12, W26 and W52 together with plasma endothelin-1 (ET-1), thiobarbituric acid-reactive substances (TBARS) and superoxide dismutase (SOD) and catalase erythrocyte activities. At W12, there was no difference between groups. At follow-up, PWV, cSBP, cPP and AIx were lower in the SRL group. The difference in PWV remained significant after adjustment for blood pressure and eGFR. In parallel, ET-1 decreased in the SRL group, while TBARS, SOD and catalase erythrocyte activities increased in both groups but to a lesser extent in the SRL group. Our results demonstrate that a CsA-free regimen based on SRL reduces aortic stiffness, plasma endothelin-1 and oxidative stress in renal recipients suggesting a protective effect on the arterial wall that may be translated into cardiovascular risk reduction.
authors.affiliation: Department of Pharmacology, Rouen University Hospital, University of Rouen, Rouen, France. robinson.joannides@chu-rouen.fr
authors.forename: R
authors.initials: R
authors.lastname: Joannidès
authors.forename: C
authors.initials: C
authors.lastname: Monteil
authors.forename: B H
authors.initials: BH
authors.lastname: de Ligny
authors.forename: P F
authors.initials: PF
authors.lastname: Westeel
authors.forename: M
authors.initials: M
authors.lastname: Iacob
authors.forename: E
authors.initials: E
authors.lastname: Thervet
authors.forename: S
authors.initials: S
authors.lastname: Barbier
authors.forename: J
authors.initials: J
authors.lastname: Bellien
authors.forename: Y
authors.initials: Y
authors.lastname: Lebranchu
authors.forename: S G
authors.initials: SG
authors.lastname: Seguin
authors.forename: C
authors.initials: C
authors.lastname: Thuillez
authors.forename: M
authors.initials: M
authors.lastname: Godin
authors.forename: I
authors.initials: I
authors.lastname: Etienne
mesh_terms: D000328:Adult; D000368:Aged; D001011:Aorta; D001794:Blood Pressure / Q000187:drug effects; D016572:Cyclosporine / Q000009:adverse effects; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D020123:Sirolimus / Q000627:therapeutic use*; D059289:Vascular Stiffness / Q000187:drug effects*
chemical_list: D019332:Endothelin-1; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D020123:Sirolimus