title: Fibrosis and evidence for epithelial-mesenchymal transition in the kidneys of patients with staghorn calculi.
abstract: OBJECTIVE
  • 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.
  
  
  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 [α-smooth muscle actin (αSMA) and vimentin] in renal tubular cells was detected by dual immunofluorescence staining. • Expression of fibronectin, transforming growth factor β₁ (TGF-β₁) 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 αSMA and vimentin were found in nephrolithiatic renal tubular cells, and these cells strongly expressed fibronectin and TGF-β₁. • 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-β₁ triggers EMT, which at least in part contributes to large stone-induced renal fibrosis.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Chanchai
authors.initials: C
authors.lastname: Boonla
authors.forename: Kerstin
authors.initials: K
authors.lastname: Krieglstein
authors.forename: Sombat
authors.initials: S
authors.lastname: Bovornpadungkitti
authors.forename: Frank
authors.initials: F
authors.lastname: Strutz
authors.forename: Björn
authors.initials: B
authors.lastname: Spittau
authors.forename: Chagkrapan
authors.initials: C
authors.lastname: Predanon
authors.forename: Piyaratana
authors.initials: P
authors.lastname: Tosukhowong
mesh_terms: D000199:Actins / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D016022:Case-Control Studies; D003404:Creatinine / Q000378:metabolism; D003430:Cross-Sectional Studies; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D007633:Keratins / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D053040:Nephrolithiasis / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D003404:Creatinine; D005353:Fibronectins; D007633:Keratins; D053773:Transforming Growth Factor beta1; D014746:Vimentin; C067980:CD68 antigen, human; D000097382:CD68 Molecule