De novo use of everolimus with elimination or minimization of cyclosporine in renal transplant recipients.

BACKGROUND: The purpose of two similarly designed multicenter, prospective, parallel-group, open-label studies was to evaluate early cyclosporine (CsA) elimination versus minimization from an everolimus-CsA-steroid regimen in de novo renal transplant patients. METHODS: Within 24 hours after transplantation, 170 renal transplant patients received everolimus (trough levels 3-8 ng/mL), CsA, and steroids. Those eligible (n = 114) were randomized (1:1) at 3 months to have CsA elimination by month 4 to 6 (±1 week) with everolimus trough levels maintained at 6 to 12 ng/mL or CsA minimization, until 12 months. The randomized population excluded those who discontinued the study prior to randomization due to adverse events, acute rejection episodes of Banff grade IIb/III, or worsening renal function during the month prior to randomization. RESULTS: At 12 months, the estimated glomerular filtration rate (Nankivell) with CsA elimination was noninferior versus CsA minimization (P < .0001, α-level 0.05; 90% confidence interval 0.6-8.5) by 7 mL/min/1.73 m(2) (noninferiority margin). Composite efficacy failure was comparable with CsA elimination and CsA minimization (18.9% and 17.5%, respectively, P = 1.000) and no graft loss or death was reported after randomization. Cytomegalovirus infections were rare under everolimus treatment, and no pneumonitis episode was reported. CONCLUSION: In our selected randomized study population, immediate initiation of everolimus allowed CsA elimination. Renal function was stable on everolimus-based, CsA-free maintenance regimen without compromising efficacy.

Preemptive kidney transplantation: experience in two centers.

INTRODUCTION: End-stage renal disease (ESRD) is a prevalent, important cause of death. Transplantation increases survival and improves the quality of life of patients with ESRD while long-term dialysis is related to poor outcomes even among patients who undergo subsequent transplantations. OBJECTIVES: To compare the advantages of preemptive procedures with kidney transplants among patients on renal replacement therapy. METHODS: This retrospective study was performed in two Córdoba city transplantation centers. Patients were divided into three groups: preemptive kidney transplant (PKT), patients on hemodialysis who received living donor kidney transplants (LDT), and subjects who received grafts from deceased donors (DDT). Serum creatinine, delayed graft function (DGF), subclinical rejection, and interstitial fibrosis/tubular atrophy (IF/TA) were evaluated at 6 months. RESULTS: Eighty patients were included: PKT (n = 28), LDT (n = 27), DDT (n = 25) mean age 29, 30, and 35 years, respectively. Women predominated among PKT and men in the other groups. In all groups, cyclosporine was the calcineurin inhibitor mostly used. Creatinine at 6 months was lower in the living donor groups (1.26 mg/dL PKT and 1.32 mg/dL LDT; P = NS) in relation to the deceased donor group (1.96 mg/dL; P < .05). DDT had the highest rate of DGF: 44% DDT versus 11.5% LDT vs 0% PKT (P < .05). Subclinical rejection was significantly lower among preemptive transplantations: PKT 7.6% versus LDT 18.5% versus DDT 24% (P < .05). IF/TA was higher in transplants from deceased donors: PKT 11.1%; LDT 11.5%; DDT 32%. CONCLUSIONS: Preemptive kidney transplantation offered the advantages of a lower creatinine, no DGF, as well as a reduced incidence of subclinical rejection and chronic allograft nephropathy at 6 months posttransplantation.