Early conversion to prednisolone/everolimus as an alternative weaning regimen associates with beneficial renal transplant histology and function: the randomized-controlled MECANO trial.
Bemelman FJ, de Fijter JW, Kers J, Meyer C, Peters-Sengers H, de Maar EF, van der Pant KA, de Vries AP, Sanders JS, Zwinderman A, Idu MM, Berger S, Reinders ME, Krikke C, Bajema IM, van Dijk MC, Ten Berge IJ, Ringers J, Lardy J, Roelen D, Moes DJ, Florquin S, Homan van der Heide JJ.
Am J Transplant. 2016 Sep 17. doi: 10.1111/ajt.14048. [Epub ahead of print]
In renal transplantation, use of calcineurin inhibitors (CNIs) is associated with nephrotoxicity and immunosuppression with malignancies and infections. This trial aimed to minimize CNI exposure and total immunosuppression while maintaining efficacy. We performed a randomized controlled, open-label multicenter trial with early cyclosporine A (CsA) elimination. Patients started with basiliximab, prednisolone (P), mycophenolate sodium (MPS) and CsA. At 6 months immunosuppression was tapered to P/CsA, P/MPS or P/EVL Primary outcomes were renal fibrosis and inflammation. Secondary outcomes were estimated glomerular filtration rate (eGFR) and incidence of rejection at 24 months. The P/MPS arm was prematurely halted. The trial continued with P/CsA (N = 89) and P/EVL (N = 96). Interstitial fibrosis and inflammation were significantly decreased and the eGFR was significantly higher in the P/EVL arm. Cumulative rejection rates were 13% (P/EVL) and 19% (P/CsA), (P = 0.08). A post hoc analysis of HLA and Donor Specific Antibodies at one year after transplantation revealed no differences. An individualized immunosuppressive strategy of early CNI-elimination to dual therapy with everolimus associated with decreased allograft fibrosis, preserved allograft function and good efficacy, but also with more SAEs and discontinuation. This can be a valuable alternative regimen in patients suffering from CNI toxicity.