Everolimus in clinical practice--renal transplantation.
Everolimus is a proliferation signal inhibitor (PSI)/mammalian target of rapamycin inhibitor that is structurally similar to sirolimus, but with a number of important pharmacokinetic differences, including a shorter half-life and time to steady state. In clinical trials, the efficacy of everolimus 1.5 mg/day and 3.0 mg/day combined with ciclosporin (CsA) and steroids in de novo renal transplant recipients is similar to that of mycophenolate mofetil, with one study showing a significantly lower risk of antibody-treated acute rejection with everolimus. When combined with reduced-dose CsA, everolimus is associated with improved renal function compared with full-dose CsA, with no decrease in efficacy. Thus, everolimus may play an important role in calcineurin inhibitor (CNI)-sparing regimens for renal transplant recipients. Studies with sirolimus have shown that CNI withdrawal is associated with a significant improvement in renal function, although there may be an increase in the risk of acute rejection. however, patient and graft survival are not adversely affected by CNI withdrawal. Notably, proteinuria <800 mg/day before conversion is a strong predictor of successful response to sirolimus treatment, and hypertensive therapy and serum lactate dehydrogenase levels may also predict response. Adverse events commonly associated with the PSIs include dyslipidaemia, proteinuria and anaemia, although these can usually be managed without difficulty. Data are also available to suggest that the PSIs are associated with a lower risk of malignancy than other immunosuppressive agents. In conclusion, everolimus may permit reduced exposure to CNIs in renal transplant recipients, with the potential to improve tolerability and renal function.
Pascual
Julio
J
Servicio de Nefrologia, Hospital Ramón y Cajal, Carretera de Colmenar, Km9.100, 28034 Madrid, Spain. jpascual.hrc@salud.madrid.org
D000208:Acute Disease; D019703:Calcineurin / Q000502:physiology; D065095:Calcineurin Inhibitors; D049109:Cell Proliferation / Q000187:drug effects; D002986:Clinical Trials as Topic; D016572:Cyclosporine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D000068338:Everolimus; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016030:Kidney Transplantation; D011183:Postoperative Complications / Q000517:prevention & control; D017410:Practice Guidelines as Topic; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D019703:Calcineurin; D020123:Sirolimus