Conversion to everolimus in kidney transplant recipients: to believe or not believe?

Abstract

Introduction: Immunosuppression with calcineurin inhibitors (CNI) in renal transplantation is associated with chronic graft dysfunction, increased cardiovascular risk, and malignancies. Everolimus (EVR) appears to permit a CNI-sparing regimen among stable kidney recipients.

Aim: The aim of this study was to analyze the efficacy and safety of conversion from CNI to EVR.

Material and methods: This was a retrospective registry-based study of all kidney transplant recipients converted from CNI to EVR between 2006 and 2010. One hundred fifty-one patients, including 69.5% males and with an overall mean age of 50.2 ± 12.7 years, underwent conversion to EVR at 37.0 ± 49.8 (16) months after transplantation with 33.7% during the first 6 months. Reasons for conversion included: CNI nephrotoxicity prevention (54.3%), chronic graft dysfunction (25.8%), malignant tumors (10.6%), CNI-adverse reactions (6.6%), and biopsy-proven CNI nephrotoxicity (2.6%). During a follow-up of 17.9 ± 9.9 months (range, 6-58.5), 18 patients (11.9%) were reconverted to CNI, 2 died with functioning grafts, and 2 lost kidney function.

Results: We observed a significant (P < .001) increase in estimated glomerular filtration rate-Modification of Diet in Renal Disease (eGFR-MDRD) by 11.3% within 6 months: 56.7 ± 22.1 to 64.1 ± 23.4 mL/min/1.73 m(2). At final evaluation it was 13.7%, namely, to 65.5 ± 23.0 mL/min/1.73 m(2). At the end of follow-up the proportion of patients with >300 mg/d proteinuria increased from 7.9% to 23.3% (P = .001). Dyslipidemia prevalence increased from 69.5% to 77.5% (P = not significant [NS]) and arterial hypertension increased from 49% to 65.9% (P < .001) at the end of follow-up. Other reported side effects included oral ulcers (2.6%), edema (5.3%), interstitial pneumonitis (1.3%), and toxic hepatitis (1.3%), some of them leading to EVR discontinuation.

Conclusion: In our population, renal function improved significantly after conversion from CNI to EVR. Although side effects were common, most were mild, withdrawal of EVR was necessary in a low percentage of cases. EVR appears to be an effective, safe alternative to CNI for maintenance therapy in selected kidney transplant recipients.