Comparative effects of sirolimus and cyclosporin on conduit arteries endothelial function in kidney recipients.
This study attempted to establish whether a calcineurin inhibitor (CNI)-free immunosuppressant regimen based on sirolimus (SRL) is associated with a preservation of conduit arteries endothelial function in kidney recipients or not. Twenty-nine kidney recipients were randomized to receive since transplantation SRL (n=15) or cyclosporin A (CsA, n=14) associated with mycophenolate mofetil (MMF) and steroids (6months) in a parallel prospective study. Systolic, diastolic blood pressures, glomerular filtration rate (GFR) and radial artery flow-mediated dilatation (FMD) induced by postischaemic hyperaemia were assessed in a blind manner at one (M1) and 7months (M7) after transplantation. Endothelium-independent dilatation was assessed by glyceryl trinitrate spray. There was no difference between the groups for all vascular parameters at M1. At M7, systolic blood pressure was lower (SRL: 119±3 vs. CsA: 138±4mmHg, P<0.05) and FMD was higher in SRL compared with CsA (SRL: 13.1±0.9 vs. CsA: 9.9±0.9%, P<0.05) without any difference for hyperaemia, endothelium-independent dilatation and GFR (SRL: 66.7±1.05 vs. CsA: 67.5±1.22ml/min). Our results demonstrate that a CNI-free regimen based on SRL and MMF prevents conduit artery endothelial dysfunction compared with CsA and MMF in kidney recipients suggesting a beneficial arterial wall effect that may also contribute to the decrease in systolic blood pressure.
Joannides
Robinson
R
Department of Pharmacology, Rouen University Hospital & INSERM U644, Institute for Biomedical Research, University of Rouen, Rouen, France. robinson.joannides@chu-rouen.fr
Etienne
Isabelle
I
Iacob
Michele
M
Hurault de Ligny
Bruno
B
Barbier
Stephane
S
Bellien
Jeremy
J
Lebranchu
Yvon
Y
Thuillez
Christian
C
Godin
Michel
M
D000328:Adult; D001158:Arteries / Q000187:drug effects; D001794:Blood Pressure; D016572:Cyclosporine / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007511:Ischemia / Q000473:pathology; D007668:Kidney / Q000187:drug effects; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020123:Sirolimus / Q000627:therapeutic use*; D013997:Time Factors
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus