The use of everolimus in renal-transplant patients

Abstract

Despite advances in immunosuppressive therapy, long-term renal-transplantation outcomes have not significantly improved over the last decade. The nephrotoxicity of calcineurin inhibitors (CNIs) is an important cause of chronic allograft nephropathy (CAN), the major driver of long-term graft loss. Everolimus is a proliferation signal inhibitor with a mechanism of action that is distinct from CNIs. The efficacy and tolerability of everolimus in renal-transplant recipients have been established in a wide range of clinical trials. Importantly, synergism between everolimus and the CNI cyclosporine (CsA) permits CsA dose reduction, enabling nephrotoxicity to be minimized without compromising efficacy. Currently, everolimus is being investigated in regimens where reduced exposure CNIs are used from the initial post-transplant period to improve renal function and prevent CAN. By inhibiting the proliferation of smooth muscle cells, everolimus may itself delay the progression or development of CAN. Although everolimus is associated with specific side effects, these can generally be managed. By targeting the main causes of short- and long-term graft loss, everolimus has a key role to play in renal transplantation, which is being explored further in a number of ongoing Phase III–IV trials.

Long-term outcome of everolimus treatment in transplant patients

“…However, biopsy-proven acute rejection occurred more frequently with everolimus 1.5 mg/day in study A2306 (25%) than in study A2307 (13.7%), suggesting that anti-IL-2 receptor induction therapy is probably beneficial for reducing the risk of early biopsy-proven acute rejection when used with a lower dose of everolimus. 32 The strength of these studies was the documentation that concentration-controlled everolimus in combination with low-exposure cyclosporine results in effective protection against rejection with good renal function (Figure 8). Later on, two further studies compared a high-dose everolimus therapy, very low-dose cyclosporine, and steroid combination with an enteric-coated mycophenolic acid, standard-dose cyclosporine, and steroid combination.…”

The Use of Everolimus for Renal-Transplant Patients with Nephrotoxicity by Calcineurin Inhibitors in our Center: Case Report

“…The lymphocyte incidence is reportedly increased if EVL use begins immediately after renal transplantation. Because EVL produces its effect by arresting the cell cycle, it is frequently used in place of a metabolic inhibitor [5,8]. In 2011, Budde et al reported that they reduced the CNI dose to diminish CNI nephrotoxicity in renal transplantation cases and switched to EVL -based immunosuppressive therapy, which proved effective [9].…”

Replacement of Mycophenolate Acid With Everolimus in Patients Who Became Neutropenic After Renal Transplant

“…Moreover, with its possible antineoplastic and antiviral properties, along with cardiovascular protection properties, it aims at improving overall patient survival. 26 In an attempt to maintain a sufficient triple immunosuppressive regimen, EVE was introduced to replace MPA, as MPA was considered responsible for resistant neutropenia. Patients in our study were relative young (range, 15-58 y), 5 of them had received 1 or 2 kidney transplants in the past and had an increased cytotoxic antibody titers, while 70% of the donors were donors with expanded criteria.…”