RE: Efficacy and safety of de novo or early everolimuswith low cyclosporine in deceased donor kidney trans-plant recipients at specified risk of delayed graft function:12-month results of a randomized, multicenter trial [1].At the present time, important new advances in clinicalkidney transplantation are limited by a number of practicaland ethical constraints that govern transplant practicearound the world. New information is dependent onrandomized controlled trials performed either at singlecenters, at a group of centers in one region, or at multiplesites around the world in which small differences are testedagainst a standard or ‘best local therapy.’ The widerthe accrual, the more applicable will be the results topopulations with demographic variables. Studies that ana-lyze the role of immunosuppressive agents have a numberof additional limitations. Trials are virtually never designedusing a single agent versus another, and must then comparethe impact of an agent as part of a multidrug regimen.Therefore, transplant clinical trials either focus on a measureof efficacy (patient and graft survival, acute rejection rates,and renal function), or safety and tolerability (measured bythe frequencies of certain side effects and/or drug discontin-uations thought to be related to the study drug). In addi-tion, funded transplant clinical trials usually vary from 6 to24 months, are limited by high cost and complexity of fol-low-up, and may miss important differences that emergeafter the study window has closed. For these reasons,10 years after the initial approval of the first in class mam-malian target of rapamycin inhibitor (mTORi) sirolimusand the recent introduction of the mTORi everolimus, weare still asking the question of how to use these agents mosteffectively. We have learned that important advantages ofmTORi class are slowing the degree of fibrosis after inflam-mation, prevention of certain cancers, possibly lower ratesof viral infections, and diminished injury to allograft kid-neys [2,3]. Important side effects attributed to these agentsinclude dyslipidemia, bone marrow suppression, impairedhealing of certain wounds, fluid collections, oral ulcers andskin rashes, pneumonitis, more proteinuria in damaged al-lografts, and hypogonadism [2–5]. In addition, some havesuggested that mTORi prolong the recovery from acutetubular necrosis after organ preservation. These advantagesand disadvantages must be weighed in each patient individ-ually, compared with the use of alternative agents.In this issue of Transplant International, the investiga-tors of the French CALLISTO study provide 1-year datafrom their randomized prospective trial of 139 DeceasedDonor kidney-only transplant recipients at intentionalhigher risk for delayed graft function (DGF). It should benoted that having one or more of the risk factors chosen,donor age >55 years, cold ischemia time range 24–40 h,and prior kidney transplant were quite modest. All patientswere given a nondepleting IL2 receptor induction antibody,cyclosporine, and steroids. The two randomized groups