Intragraft Tubular Vimentin and CD44 Expression Correlate With Long-Term Renal Allograft Function and Interstitial Fibrosis and Tubular Atrophy

Abstract

Development of interstitial fibrosis and tubular atrophy (IF/TA) is the main histologic feature involved in renal allograft deterioration. The aim of this study was to validate whether de novo tubular expression of CD44 (transmembrane glycoprotein) and vimentin (mesenchymal cell marker), both involved in renal fibrosis, can operate as surrogate markers for late IF/TA and renal function. Furthermore, we wanted to establish the interrater reproducibility for the scoring system, which can be a problem in histologic assessments. Six-month protocol renal allograft biopsies (n=30 for matching 12 months estimated glomerular filtration rate (eGFR) from which 20 matched the 12-month protocol biopsy) were immunostained for CD44 and vimentin, semiquantitatively scored by three observers of two centers, and correlated with IF/TA and eGFR at 12 months. The interobserver agreement was excellent for CD44 (Kendall's W-coefficient: 0.69; P<0.001) and vimentin (Kendall's W-coefficient: 0.79; P<0.001). CD44 and vimentin expression at 6 months were significantly correlated with IF/TA (rho=0.481 for CD44 and rho=0.619 for vimentin) and eGFR (rho=-0.569 for CD44 and rho=-0.376 for vimentin) at 12 months. Summarizing, de novo tubular expression of CD44 and vimentin can function as surrogate marker for IF/TA and eGFR at 12 months. Further area under receiver operator characteristic curve analysis has to establish the predictive value for both biomarkers.