Conversion from a calcineurin inhibitor to everolimus therapy in maintenance liver transplant recipients: a prospective, randomized, multicenter trial.

Calcineurin inhibitors (CNIs) contribute to renal dysfunction following liver transplantation. This prospective, randomized, multicenter, 6-month study (with an additional 6 months of follow-up) evaluated whether everolimus with CNI reduction or discontinuation would improve renal function in maintenance liver transplant recipients experiencing CNI-related renal impairment. Patients started everolimus therapy with CNI reduction or discontinuation (n = 72) or continued receiving standard-exposure CNI (n = 73). At month 6, 80% of the patients who had converted to everolimus had discontinued the CNI. The mean change in creatinine clearance (CrCl) from baseline to month 6 was similar between groups (everolimus, 1.0 +/- 10.2 mL/minute; controls, 2.3 +/- 7.8 mL/minute; P = 0.46), so the primary study endpoint (8 mL/minute difference in the change in CrCl) was not achieved. Among patients who continued everolimus according to the protocol, the mean increase in CrCl was 2.1 (n = 53) and 3.8 mL/minute (n = 38) at months 6 and 12, respectively, versus 2.4 (n = 68) and 3.5 mL/minute in controls (n = 51). The high frequency of CNI dose reductions in controls (77% of the patients) and the relatively long mean time post-transplant (>3 years) likely contributed to the small difference in CrCl. Biopsy-proven acute rejection occurred in 1.4% of the patients in each group, with no graft losses. Study drug discontinuation was higher in everolimus-treated patients, and adverse events were more frequent. These data demonstrate that everolimus allows for discontinuation or a major reduction of CNI exposure in liver allograft recipients suffering CNI-related renal dysfunction without a loss of efficacy. Trials targeting earlier conversion post-transplantation are required to confirm the efficacy and safety of everolimus for improving renal function after liver transplantation.

De Simone P ，Metselaar HJ ，Fischer L ，Dumortier J ，Boudjema K ，Hardwigsen J ，Rostaing L ，De Carlis L ，Saliba F ，Nevens F ... -  《-》

Everolimus with reduced calcineurin inhibitor in thoracic transplant recipients with renal dysfunction: a multicenter, randomized trial.

Gullestad L ，Iversen M ，Mortensen SA ，Eiskjaer H ，Riise GC ，Mared L ，Bjørtuft O ，Ekmehag B ，Jansson K ，Simonsen S ，Gude E ，Rundqvist B ，Fagertun HE ，Solbu D ，Bergh CH ... -  《-》

Improvement of renal function after the switch from a calcineurin inhibitor to everolimus in liver transplant recipients with chronic renal dysfunction.

Castroagudín JF ，Molina E ，Romero R ，Otero E ，Tomé S ，Varo E ... -  《-》

Long-term results in renal transplant patients with allograft dysfunction after switching from calcineurin inhibitors to sirolimus.

Bumbea V ，Kamar N ，Ribes D ，Esposito L ，Modesto A ，Guitard J ，Nasou G ，Durand D ，Rostaing L ... -  《NEPHROLOGY DIALYSIS TRANSPLANTATION》

Conversion of long-term kidney transplant recipients from calcineurin inhibitor therapy to everolimus: a randomized, multicenter, 24-month study.

Holdaas H ，Rostaing L ，Serón D ，Cole E ，Chapman J ，Fellstrøm B ，Strom EH ，Jardine A ，Midtvedt K ，Machein U ，Ulbricht B ，Karpov A ，O'Connell PJ ，ASCERTAIN Investigators ... -  《-》