Early Epithelial Phenotypic Changes Predict Graft Fibrosis

• Published in: Journal of the American Society of Nephrology Vol. 19; no. 8; pp. 1584 - 1591
• Main Authors: HERTIG, Alexandre, ANGLICHEAU, Dany, LEGENDRE, Christophe, RONDEAU, Eric, XU-DUBOIS, Yi-Chun, VERINE, Jérome, PALLET, Nicolas, TOUZOT, Maxime, ANCEL, Pierre-Yves, MESNARD, Laurent, BROUSSE, Nicole, BAUGEY, Edith, GLOTZ, Denis
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.08.2008; American Society of Nephrology
• Subjects: Adult; Biological and medical sciences; Biopsy; Cell Transdifferentiation; Clinical Research; Epithelial Cells - pathology; Female; Fibrosis; Humans; Kidney - pathology; Kidney Function Tests; Kidney Transplantation - adverse effects; Kidneys; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Nephrosclerosis - pathology; Phenotype; Risk Factors; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the urinary system; Transplants; Urinary system involvement in other diseases. Miscellaneous; Urothelium - pathology; Kidney disease; Human; Nephrology; Urinary system disease; Renal fibrosis; Transplantation; Homotransplantation; Kidney; Urology; Phenotype; Surgery; Graft; Epithelial cell; Complication; Early; Predictive factor
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/asn.2007101160

Chronic allograft nephropathy accounts for the loss of approximately 40% of allografts at 10 yr. Currently, no biomarker is available to detect interstitial fibrosis and tubular atrophy in the renal graft at an early stage, when intervention may be beneficial. Because tubular epithelial cells have been shown to exhibit phenotypic changes suggestive of epithelial-to-mesenchymal transition, we studied whether these changes predict the progression of fibrosis in the allograft. Eighty-three kidney transplant recipients who had undergone a protocol graft biopsy at both 3 and 12 mo after transplantation were enrolled. De novo vimentin expression and translocation of beta-catenin into the cytoplasm of tubular cells were detected on the first biopsy by immunohistochemistry. Patients with expression of these markers in >or=10% of tubules at 3 mo had a higher interstitial fibrosis score at 1 yr and a greater progression of this score between 3 and 12 mo. The intensity of these phenotypic changes positively and significantly correlated with the progression of fibrosis, and multivariate analysis showed that their presence was an independent risk factor for this progression. In addition, the presence of early phenotypic changes was associated with poorer graft function 18 mo after transplantation. In conclusion, early phenotypic changes indicative of epithelial-to-mesenchymal transition predict the progression toward interstitial fibrosis in human renal allografts.