title: A randomized exploratory trial of steroid avoidance in renal transplant patients treated with everolimus and low-dose cyclosporine.
abstract: 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.
authors: Nephrology Unit, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, IRCCS, Milan, 20122, Italy. monta@policlinico.mi.it
authors: Giuseppe
authors: G
authors: Montagnino
authors: Silvio
authors: S
authors: Sandrini
authors: Beniamino
authors: B
authors: Iorio
authors: Francesco Paolo
authors: FP
authors: Schena
authors: Mario
authors: M
authors: Carmellini
authors: Paolo
authors: P
authors: Rigotti
authors: Maria
authors: M
authors: Cossu
authors: Paolo
authors: P
authors: Altieri
authors: Maurizio
authors: M
authors: Salvadori
authors: Sergio
authors: S
authors: Stefoni
authors: Giuseppe
authors: G
authors: Corbetta
authors: Claudio
authors: C
authors: Ponticelli
mesh_terms: D000328:Adult; D016572:Cyclosporine / Q000008:administration & dosage*; D000068338:Everolimus; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D011241:Prednisone; D020123:Sirolimus