Histological Progression of Interstitial Fibrosis/Tubular Atrophy (IF/TA) According to Epithelial-Mesenchymal Transition (EMT) Profile: The CERTITEM Trial

作者：Lionel Rostaing, Alexandre Hertig, Luisa Albano, Dany Anglicheau, Antoine Dürrbach, Olivier Toupance, Bruno Moulin, Pierre Merville, Marc Hazzan, Puyi Lang, Guy Touchard, Bruno Hurault de Ligny, Stéphane Quéré, F. Di Giambattista, Yaëlle Dubois, Eric Rondeau · 发表于：Transplantation · 年份：2012 · DOI：10.1097/00007890-201211271-00001 · 被引用次数：4 · 研究领域：Oral and gingival health research、Renal Transplantation Outcomes and Treatments、Organ and Tissue Transplantation Research

Introduction: Tubular expression of vimentin and cytoplasmic translocation of β-catenin, consistent with epithelial to mesenchymal transition (EMT), may predict IF/TA and thus help identify patients at increased risk for calcineurin inhibitor (CNI)-related nephrotoxicity who could benefit from conversion to the mTOR inhibitor everolimus. Methods: CERTITEM was a prospective, multicenter, randomized, open-label trial of de novo kidney transplant recipients. Key exclusion criteria were (a) at transplant: PRA >20%, positivity for class I or II anti-HLA donor specific antibodies (DSA), cold ischemia time >30h and proteinuria >0.8g/24h (b) at randomization: biopsy-proven acute rejection (BPAR) or subclinical acute rejection on protocol biopsies, DSA-positivity, calculated eGFR (MDRD4) < 30mL/min and proteinuria >0.8g/24h. All patients received CsA with enteric-coated mycophenolic acid (EC-MPS), IL-2RA induction and oral steroids. Patients were stratified by centrally-analyzed EMT status on month 3 protocol biopsy, then randomized from month 4 to continue their current regimen (CsA) or start everolimus (C0 6-10ng/mL) with EC-MPS. EMT+ was defined as ≥10% tubular cells showing de novo expression of vimentin (or translocation of β-catenin if inconclusive) into the cytoplasm (EMT score ≥2). Primary endpoint is progression of centrally-analyzed IF/TA (score increase ≥1) during months 3-12 in patients EMT+ at month 3. Characteristics of randomized patients at month 3 will be described, a...