Conversion from sirolimus to everolimus in maintenance renal transplant recipients within a calcineurin inhibitor-free regimen: results of a 6-month pilot study.

Aim: To provide data on conversion of kidney transplant patients from sirolimus to everolimus.
Materials and Methods: In this 6-month prospective, open-label pilot study, maintenance renal transplant patients receiving sirolimus, mycophenolic acid and corticosteroids without concomitant calcineurin inhibitor (CNI) therapy were converted to everolimus 8 mg/day (8 - 15 ng/ml), and followed for 6 months. Mycophenolic acid and corticosteroid therapy were continued unchanged. Patients with acute rejection within the previous 3 months were excluded.
Results: 11 patients were recruited and completed the study (mean 5.1 +/- 1.8 years post transplant). Mean everolimus trough level remained within target throughout the study. Mean GFR remained stable (Day 0, 48.4 +/- 8.4 ml/min/1.73 m2, Month 6, 49.5 +/- 17.3 ml/ min/1.73 m2 (p = 0.966), as did mean renal phosphate threshold (TmPO4/GFR) (Day 0, 0.41 +/- 0.15 mmol/l, Month 6, 0.40 +/- 0.17 mmol/l (p = 0.966)). Serum phosphates increased significantly from 0.71 to 0.77 mmol/l (p = 0.01), but tubular reabsorption of phosphates and 24-h phosphaturia remained unchanged and mean PTH concentration tended to decrease. No patient died, lost their graft or experienced biopsy-proven acute rejection after conversion. There were no cases of CMV infection. Tolerability remained similar post conversion. Hematological and lipid parameters remained stable. Liver enzymes and sex hormones remained within normal ranges.
Conclusion: This pilot study suggests that converting kidney transplant patients receiving CNI-free maintenance immunosuppression from sirolimus to everolimus, at relatively high exposure levels, is safe and easily manageable. There was no consistent evidence for a change in GFR or proximal tubular function.