Fibrosis Progression According to Epithelial‐Mesenchymal Transition Profile: A Randomized Trial of Everolimus Versus CsA

摘要: Markers of epithelial-mesenchymal transition (EMT) may identify patients at high risk graft fibrogenesis who could benefit from early calcineurin inhibitor (CNI) withdrawal. In a randomized, open-label, 12-month trial, de novo kidney transplant received cyclosporine, enteric-coated mycophenolate sodium (EC-MPS) and steroids to month 3. Patients were stratified as EMT+ or EMT- based on 3 biopsy, then randomized start everolimus with half-dose EC-MPS (720 mg/day) cyclosporine withdrawal (CNI-free) continue standard (CNI). The primary endpoint was progression fibrosis (interstitial fibrosis/tubular atrophy [IF/TA] grade increase ≥1 between months 3-12) in patients. 194 (96 CNI-free, 98 CNI); 153 (69 84 CNI) included histological analyses. Fibrosis occurred 46.2% (12/26) CNI-free versus 51.6% (16/31) CNI (p = 0.68). Biopsy-proven acute rejection (BPAR, including subclinical events) 25.0% 5.1% patients, respectively (p < 0.001). conclusion, initiation does not prevent interstitial fibrosis. Using this protocol, which exposure relatively low administered EC-MPS, overwhelmingly under-immunosuppressed experienced an increased BPAR.