Abstract number: 951308

Abstract Number: 951308
Contact/Presenting Author Evaldo Favi, MD , Roma - Italy
Abstract Title: A prospective trial comparing Tacrolimus
with Everolimus and low dose Cyclosporine

Evaldo Favi, MD1, Franco Citterio, MD1, Gionata Spagnoletti, MD1, Vincenzo Tondolo,
MD1, Jacopo Romagnoli, MD1 and Marco Castagneto, MD1. 1Surgery, Catholic University,
Rome, Italy.
Body: Introduction. Reduction or avoidance of calcineurin inhibitors is a major issue in
current immunosuppressive strategy. Aim of this study was to compare a calcineurine based
to a calcineurine sparing immunosuppressive regimen. We performed a prospective,
randomized trial in renal transplantation comparing tacrolimus-MMF-prednisone (TAC) to
everolimus-cyclosporine-prednisone (EVE).
Methods. Sixty cadaveric renal transplant recipients were randomized to TAC (30 pts) or
EVE (30 pts) and followed up to 6 months. Tacrolimus was dosed aiming at a through blood
level of 8-10 ng/ml by months 3 and 5-8 ng/ml thereafter. Everolimus was dosed aiming at a
through blood level of 3 -12 ng/ml and CsA was dosed aiming at a C2 level of 350 - 700
ng/ml.
Results. Demographic characteristics of pts were similar in the two groups (age years
46+10, vs 44+12; male/female ratio 18/12 vs 15/15, time on dialysis months 42+29 vs
44+30; CIT hours 13.3+3.5 vs 12.6+3.2; HLA match 3.2+1 vs 2.9+0.94 p=ns). At 6 months,
patient and graft survival were similar in the two groups (TAC: PTSurv 100%, GSurv
96.7%; EVE: PTSurv 100%, GSurv 93.33%; (p=ns). The incidence of clinical acute
rejection at 1 and 6 months were higher in the EVE group but not significantly different (1
m TAC 10% vs EVE 16.7; 6 m TAC 16.7% vs EVE 26.7% p=ns). No difference in mean
creatinine clearance (calculated Cockroft-Gault) at 6 months was found between TAC and
EVE groups (62±23 mL/min vs. 60±17 mL/min, p=ns). Significantly more patients in the
EVE group had dislipidemia and were receiving statines respect to the TAC group (TAC vs
EVE: total cholesterol 202±39 vs 255±60 p< 0.027; statines use 18% vs 44%, p< 0.05).
Significantly more adjustments of the immunosuppressive dosages were required in the
EVE group (dose adjustments/pt EVE 8.86 vs 5.54 p=0.025).
Conclusions. These short term data show that tacrolimus-MMF-prednisone regimen
produces similar acute rejection rates, graft survival and renal function 6 months after renal
transplantation, compared to everolimus-cyclosporine-prednisone, but has better
cardiovascular profile and requires less dose adjustments.
Abstract Number: 951322
Contact/Presenting Author Jacopo Romagnoli, MD

Abstract Title: Low Everolimus exposure is associated with higher incidence of acute
rejection in renal allograft recipients
Jacopo Romagnoli, MD1, Franco Citterio, MD1, Evaldo Favi, MD1, Gionata Spagnoletti, MD1,
Vincenzo Tondolo, MD1, Maria Paola Salerno, MD1 and Marco Castagneto, MD1. 1Surgery,
Catholic University, Rome, Italy.
Body: Introduction. Everolimus (EVE) has shown a potential for reduction of nephrotoxicity
associated with cyclosporine (CsA), providing the same protection against rejection. We
analyzed the relationship between the incidence of acute rejection (AR) and Everolimus
exposure in 20 cadaveric renal transplant recipients treated with the combination of EVE +
CsA.
Methods. Immunosuppression consisted of basiliximab induction given pre transplant and on
day 4 post-transplant, EVE was given at a starting dose of 1.5 mg/day then concentration
controlled aiming at trough levels of 3-8 ng/ml by day 7, CsA was given at a starting dose of 4
mg/kg/day and then concentration controlled with C2 monitoring (C2 500-700 ng/ml), steroids
were tapered in order to reach a standard dose of 5 mg by day 30. EVE (trough) and CsA (C2)
exposures were measured at day 3 and 7 post-transplantation and related with the incidence of
AR in the first 3 months post-tx. Data were analyzed for pts with or without AR episodes.
Results. Demographic characteristics of pts were similar in the two groups (recipient age;
male/female ratio; donor age, donor creatinine, CIT, HLA match). The overall incidence of
AR was 25% (5/20 pts). On post-op day 7 patients with AR had significantly lower EVE
trough concentrations respect to patients not experiencing AR (No AR) (AR vs no AR: 2.2 2.1
vs 4.8 2.4 ng/ml, p=0.05). No patient experiencing AR had reached the lower target of 3 ng/ml
EVE trough concentration. In AR pts CsA C2 values were also very close to the lower end of
the target range on day 3 (583 334 ng/ml), but all pts were in the range by day 7. All rejecting
grafts were functioning 3 months post-transplantation, but mean serum creatinine was higher
in the AR group (AR vs no AR 2.2 0.7 vs 1.1 0.2 mg/dl, p=0.04).
Conclusions. When Everolimus is used in combination with low dose CsA, in order to protect
kidney transplant patients from the risk of acute rejection, the threshold of 3 ng/ml EVE trough
concentration must be reached in the first week post transplantation. Careful monitoring of
Everolimus exposure and higher Everolimus starting doses are suggested.

Source: http://www.aieconlus.it/chiehtml/chie/Favi%20Evaldo/FaviEvaldo2.pdf