Fibrosis and evidence for epithelial-mesenchymal transition in the kidneys of patients with staghorn calculi

OBJECTIVES To quantify fibrotic lesions in renal tissues obtained from patients with large calculi and to evaluate association with renal function. Presence of epithelial-mesenchymal transition (EMT) in stone-containing renal tissues was investigated. PATIENTS, SUBJECTS AND METHODS In all, 50 patients with nephrolithiasis with large calculi and matched healthy controls (37) were recruited. Plasma creatinine (Cr) and corrected Cr clearance (CCr) were determined in all subjects. Of the 50 patients, 38 had renal tissue available for histological analysis. Fibrosis was assessed by Masson's trichrome staining. Co-expression of epithelial cytokeratins and mesenchymal markers [a smooth muscle actin (alpha SMA) and vimentin] in renal tubular cells was detected by dual immunofluorescence staining. Expression of fibronectin, transforming growth factor beta(1) (TGF-beta(1)) and CD68 were investigated. RESULTS Overall, the kidney function of the patients was significantly reduced, indicated by increased plasma Cr and decreased corrected CCr compared with healthy controls. Inflammation grading in renal tissues of the patients was correlated with the percentage of the fibrotic area. Renal fibrosis was inversely correlated with renal function. Cytokeratins co-expressed with alpha SMA and vimentin were found in nephrolithiatic renal tubular cells, and these cells strongly expressed fibronectin and TGF-beta(1). Infiltration of CD68-positive cells was a common finding in the inflamed renal sections. CONCLUSIONS Kidneys of large stone-forming patients had robust signs of inflammation and fibrosis, and there was a close correlation of renal fibrosis with renal dysfunction. This is the first study to show evidence for renal tubular cells showing signs of EMT in large stone-containing kidneys. Plausibly, TGF-beta(1) triggers EMT, which at least in part contributes to large stone-induced renal fibrosis.