Switch of immunosuppression from cyclosporine A to everolimus: impact on pulse wave velocity in stable de-novo renal allograft recipients.
BACKGROUND
Cardiovascular mortality is extraordinarily high in renal allograft recipients and accounts for almost half of all allograft losses. Whereas the immunosuppression with calcineurin inhibitors is associated with an increased cardiovascular risk, beneficial effects of mammalian target of rapamycin inhibitors on the vascular system are suspected.


METHODS
In a randomized clinical trial, we evaluated the impact on pulse wave velocity (PWV) of a switch from cyclosporine A (CsA) to everolimus (EVR), 6 months after transplantation, in 27 stable de-novo renal allograft recipients. PWV was assessed before and after randomization to the different immunosuppressive protocols at 6 and 15 months post-transplantation, respectively. Seventeen out of 27 patients included in the analysis were switched to EVR; 10 out of 27 were kept on CsA.


RESULTS
The switch of immunosuppressive therapy from CsA to EVR resulted in stable PWV (9.50+/-1.92 vs. 9.13+/-1.62 m/s, DeltaPWV= -0.37+/-1.14 m/s, P=0.16), whereas a significant increase of PWV (9.93+/-1.94 vs. 10.8+/-2.24 m/s, DeltaPWV=0.89+/-1.47 m/s, P=0.03) was observed in patients on continued CsA therapy.


CONCLUSIONS
In renal allograft recipients, the prolonged treatment with CsA was associated with a significant increase of PWV whereas no further deterioration of large vessel compliance was observed in patients that were switched to EVR 6 months post transplantation. The cardiovascular risk profile in stable de-novo renal allograft recipients might therefore be positively impacted by an early switch of the primary immunosuppressive therapy from CsA to EVR.
Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany. joerg.seckinger@med.uni-heidelberg.de
Joerg
J
Seckinger
Claudia
C
Sommerer
Ulrich-Paul
UP
Hinkel
Oskar
O
Hoffmann
Martin
M
Zeier
Vedat
V
Schwenger
D001158:Arteries / Q000187:drug effects* / Q000503:physiopathology; D001783:Blood Flow Velocity / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D000068338:Everolimus; D005260:Female; D006801:Humans; D016867:Immunocompromised Host / Q000502:physiology; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011673:Pulsatile Flow / Q000187:drug effects*; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D020123:Sirolimus