NDT Advance Access published online on September 21, 2007
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfm621
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A randomized exploratory trial of steroid avoidance in renal transplant patients treated with everolimus and low-dose cyclosporine
1Nephrology Unit, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, IRCCS, Milan, 20122, 2Nephrology Unit, Spedali Civili, Brescia, 25123, 3Medicine Faculty, University of Tor Vergata, Rome, 00133, 4Nephrology Unit, University of Bari, 70124, 5Nephrology Unit, Policlinico Le Scotte, Siena, 53100, 6Medical Sciences Department, University of Padua, 35100, 7Nephrology Unit, Ospedale Civile, Sassari, 07100, 8Nephrology Unit, Ospedale Brotzu, Cagliari, 09134, 9Nephrology Unit, Policlinico Careggi, Florence, 50139, 10Nephrology Unit, S. Orsola University Hospital, Bologna, Italy, 40138, 11Medical Department, Novartis Pharma S.p.A., Origgio, 20140 and 12Medical Consultant, IRCCS, Istituto Auxologico, Milan, 20145, Italy
Correspondence and offprint requests to: Giuseppe Montagnino, Divisione di Nefrologia, IRCCS Ospedale Maggiore, Via della Commenda 15, 20122 Milano, Italy. Email: monta{at}policlinico.mi.it
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Abstract |
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Background. Everolimus and cyclosporine exhibit synergistic immunosuppressive activity when given in combination. In this randomized trial, we explored whether the use of everolimus associated with low-dose cyclosporine could allow an early avoidance of steroids in de novo renal transplant recipients.
Methods. In this exploratory multicenter trial, 65 out of 133 patients treated with basiliximab (days 0 and 4), everolimus 3 mg/day and cyclosporine were randomized to stop steroids on the seventh post-transplant day (group A), whereas the remaining 68 continued low-dose steroid treatment (group B).
Results. During the follow-up, 30 patients of group A (46%) resumed steroids. According to the intention-to-treat analysis, the 3-year graft survival rate was 95% in group A and 87% in group B (P = ns). There were more biopsy-proven rejections in group A, the difference being of borderline significance (32% vs 18%; P = 0.059). After 3 years, mean creatinine clearance was 52.3 ± 17.1 ml/min in group A and 52.2 ± 21.5 ml/min in group B. It was similar in the group A patients who experienced rejection (49.8 ± 14.7 ml/min) and those who did not (53.6 ± 18.3 ml/min; P = 0.319). Mean serum cholesterol and triglyceride levels were, respectively, less than 250 mg/dl and less than 200 mg/dl in both groups, without any significant difference. Vascular thrombosis (0 vs 11.7%; P = 0.0043) was more frequent in group B.
Conclusions. Treatment based on everolimus and low-dose cyclosporine allowed excellent renal graft survival and stable graft function at 3 years. An early discontinuation of steroids increased the risk of acute rejection, but was associated with a better graft survival in the long-term. However, it was well tolerated only by 54% of patients.
Keywords: basiliximab everolimus and cyclosporine immunosuppression: cyclosporine; early steroid withdrawal; everolimus; kidney transplant; steroid free
Received for publication: 14. 5.07
Accepted in revised form: 16. 8.07