Benefit of early conversion from CNI-based to everolimus-based immunosuppression in heart transplantation

Gude, Einar; Gullestad, Lars; Arora, Satish; Simonsen, Svein; Hoel, Ina; Hartmann, Anders; Holdaas, Hallvard; Fiane, Arnt E.; Geiran, Odd R.; Andreassen, Arne K.

doi:10.1016/j.healun.2010.01.005

« Previous Next »The Journal of Heart and Lung Transplantation
Volume 29, Issue 6 , Pages 641-647, June 2010

Benefit of early conversion from CNI-based to everolimus-based immunosuppression in heart transplantation

Einar Gude, MD
- Department of Cardiology, Oslo University Hospital, Oslo, Norway
- Reprint requests: Einar Gude, MD, Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo 0027, Norway. Telephone: +47-23-07-00-00. Fax: +47-23-07-19-50
Lars Gullestad, MD, PhD
- Department of Cardiology, Oslo University Hospital, Oslo, Norway
- Rikshospitalet and Faculty Division, University of Oslo, Oslo, Norway
Satish Arora, MD
- Rikshospitalet and Faculty Division, University of Oslo, Oslo, Norway
Svein Simonsen, MD, PhD
- Department of Cardiology, Oslo University Hospital, Oslo, Norway
Ina Hoel, RN
- Department of Cardiology, Oslo University Hospital, Oslo, Norway
Anders Hartmann, MD, PhD
- Rikshospitalet and Faculty Division, University of Oslo, Oslo, Norway
- Department of Internal Medicine, Oslo University Hospital, Oslo, Norway
Hallvard Holdaas, MD, PhD
- Department of Internal Medicine, Oslo University Hospital, Oslo, Norway
Arnt E. Fiane, MD, PhD
- Rikshospitalet and Faculty Division, University of Oslo, Oslo, Norway
- Department of Thoracic and Cardiovascular Surgery, Oslo University Hospital, Oslo, Norway
Odd R. Geiran, MD, PhD
- Rikshospitalet and Faculty Division, University of Oslo, Oslo, Norway
- Department of Thoracic and Cardiovascular Surgery, Oslo University Hospital, Oslo, Norway
Arne K. Andreassen, MD, PhD
- Department of Cardiology, Oslo University Hospital, Oslo, Norway

published online 22 March 2010.

Background

Calcineurin inhibitor (CNI)-induced nephrotoxicity is a feared adverse effect after heart transplantation (HTx). In patients with advanced renal failure we performed an overnight conversion from cyclosporine (CsA) to everolimus within the first year after HTx and compared changes in renal function to a similar switch performed in a group of long-term HTx survivors with 24-month follow up.

Methods

Sixteen HTx recipients (Group 1), including 5 patients undergoing dialysis, were switched overnight from CsA to everolimus at 5.5 (range 1.3 to 8.5) months post-operatively, whereas 15 patients completed 24 months of follow-up. Fifteen long-term survivors (Group 2) were recruited at 96 (58 to 148) months post-HTx. Due to 3 withdrawals and 2 deaths, 10 of these 15 patients remained available for follow-up assessment.

Results

In Group 1 patients, creatinine level improved from 211 (186 to 263) to 112 (98 to 140) μmol/liter and estimated glomerular filtration rate (eGFR) from 29 (20 to 35) to 62 (43 to 69) ml/min/1.73 m² (p < 0.001). In Group 2, creatinine decreased from 227 (188 to 255) to 193 (150 to 250) μmol/liter (p = 0.299), and eGFR increased from 26 (21 to 31) to 28 (22 to 35) ml/min/1.73 m² (p = 0.225). Four cellular rejections were treated successfully in Group 1. All together, 24 adverse events occurred.

Conclusions

These preliminary data are the first to suggest that the improvement in renal function after switching to CNI-free everolimus treatment has the greatest potential within the first year post-HTx. While we await randomized, controlled trials, it appears that conversion can be performed with acceptable safety in selected patients.

Keywords: heart transplantation, immunosuppression, renal failure, everolimus, rejections