Thirty-four recipients 1 to 4 years after HT and with 25 to 60 ml/min of creatinine clearance (CrCl) were randomized to everolimus with a very low dose (C0: 50 to 90 ng/ml, n = 17) or MMF with low dose of cyclosporine (C0: 100 to 150 ng/ml, n = 17). Follow-up was prolonged up to 3 years, and calculated CrCl was the main efficacy measure.
Cyclosporine was maintained at 70 % and 30 % lower than baseline in the everolimus and MMF arms, respectively, throughout the 3-year study period. CrCl remained stable in the everolimus patients (+7 % from baseline; p = 0.7), but improved in the MMF patients (+20 % from baseline; p < 0.01), with a trend toward improved values compared with everolimus patients (46 ¡À 12 vs 56 ¡À 15 ml/min; p = 0.06). Subgroup analysis revealed that baseline proteinuria markedly influenced the renal function response to everolimus: whereas in patients with baseline proteinuria CrCl significantly worsened (?0 % ; p = 0.04), it improved in those without (+15 % ; p = 0.03). Safety was comparable between the two study arms.
Cyclosporine nephrotoxicity improved after a prolonged dose reduction in patients receiving MMF. The everolimus-based strategy provided a similar benefit only to patients without baseline proteinuria. While raising caution against the universal use of everolimus for kidney protection, our long-term results support the need for customized approaches in the management of drug toxicities in maintenance HT recipients.