Skip to Content
MilliporeSigma
  • Safety and efficacy of the early introduction of everolimus with reduced-exposure cyclosporine a in de novo kidney recipients.

Safety and efficacy of the early introduction of everolimus with reduced-exposure cyclosporine a in de novo kidney recipients.

Transplantation (2014-07-02)
Chang-Kwon Oh, Kyu Ha Huh, Jongwon Ha, Yeong Hoon Kim, Yong-Lim Kim, Yu Seun Kim
ABSTRACT

Everolimus and cyclosporine A (CsA) exhibit synergistic immunosuppressive activity when used in combination. We examined the safety and efficacy of the use of everolimus with a cyclosporine-sparing strategy in de novo renal transplant recipients. A comparative, parallel, randomized, open-label 1-year study has been performed in 148 patients from five transplant centers to compare the efficacy and tolerability of everolimus and reduced exposure CsA (the investigational group) or enteric-coated mycophenolate sodium and standard-exposure CsA (the control group) in combination with basiliximab and steroids. The eligible subjects were randomly assigned at 1 month after transplantation. Efficacy failure (biopsy-proven acute rejection, death, graft loss, or loss to follow-up), safety, and renal function were evaluated. One graft loss has been reported in the control group and no patient death were reported in either group. The incidence of biopsy-proven acute rejection until 12 months after transplantation of the investigational group was 7.5%, compared to 11.1% of the control group (P=0.565). The mean estimated glomerular filtration rates of the investigational group at 12 months after transplantation was significantly higher (68.1 ± 16.8 ml/min/1.73 m(2)) than that of the control group (60.6 ± 15.8 ml/min/1.73 m(2); P=0.016). There was no significant difference (P>0.05) in the incidence of discontinuations and serious adverse events between the groups. The results of this study provide the evidences that (1) the calcineurin inhibitor (CNI) minimization by the introduction of everolimus after 1-month posttransplantation keeps the incidences of acute rejection and additional risks as low as the conventional immunosuppression; (2) it allows minimizing CNI exposure, consequently reducing CNI nephrotoxicity and preserving renal function.

MATERIALS
Product Number
Brand
Product Description

Supelco
Sirolimus solution, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®
Supelco
Cyclosporin A, VETRANAL®, analytical standard
Supelco
Mycophenolic acid solution, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
Cyclosporin A, 97.0-101.5% (on dried basis)
Sigma-Aldrich
Cyclosporin A, BioReagent, from Tolypocladium inflatum, for molecular biology, ≥95%
Sigma-Aldrich
Cyclosporin A, from Tolypocladium inflatum, ≥95% (HPLC), solid
Sigma-Aldrich
Mycophenolate mofetil, ≥98% (HPLC)
Mycophenolate mofetil, European Pharmacopoeia (EP) Reference Standard
Supelco
Everolimus solution, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®
USP
Mycophenolate mofetil, United States Pharmacopeia (USP) Reference Standard
Supelco
Cyclosporine, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Rapamycin, VETRANAL®, analytical standard
Sigma-Aldrich
Mycophenolic acid, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Mycophenolic acid, ≥98%
Supelco
Mycophenolic acid, analytical standard
Ciclosporin, European Pharmacopoeia (EP) Reference Standard
Supelco
Cyclosporin A solution, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
Rapamycin from Streptomyces hygroscopicus, ≥95% (HPLC), powder
Mycophenolate mofetil for peak identification, European Pharmacopoeia (EP) Reference Standard