title: Novel evidence demonstrates that epithelial-mesenchymal transition contributes to nephrolithiasis-induced renal fibrosis.
abstract: OBJECTIVE
  To investigate fibrotic lesions in renal tissues obtained from patients with large calculi, and to selectively evaluate the expression and clinical significance of Twist and E-cadherin in nephrolithiasis patients.
  
  
  METHODS
  We recruited 50 patients with kidney stone and 32 matched healthy controls. We determined plasma creatinine (Cr) and corrected Cr clearance (CCr). For the 50 patients, we detected daily urine protein excretion. At the end of percutaneous nephroscopic lithotomy, we performed puncture biopsy to acquire kidney tissue. We obtained normal control kidney tissues from non-nephrolithiasis patients who received a surgical biopsy during open surgery. We determined the expression of Twist and E-cadherin by immunohistochemical staining and scored it with clinical parameters. In addition, we analyzed the degree of expression of Twist and its correlation with long-term renal survival.
  
  
  RESULTS
  Overall, the renal function of patients significantly decreased, as indicated by Cr and reduced CCr compared with healthy controls. Activated Twist was strongly expressed in tubular epithelial cells from kidneys of nephrolithiasis patients, whereas we found little positive staining of Twist in normal kidneys. Meanwhile, the expression of E-cadherin was significantly suppressed in kidneys of nephrolithiasis patients. Twist expression was inversely correlated with E-cadherin expression; using multivariate analysis, data showed that the factors influencing renal survival in patients were CCr (relative ratio, 4.39; 95% confidence interval, 1.34-14.38; P = 0.013) and the extent of Twist expression (relative ratio, 3.45; 95% confidence interval, 1.10-10.68; P = 0.033).
  
  
  CONCLUSIONS
  Our data suggest that the possible novel EMT marker molecule Twist and Twist staining might be a valuable index predicting renal fibrosis progression in human nephrolithiasis.
authors.affiliation: Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Yong-Zhen
authors.initials: YZ
authors.lastname: Liu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Feng
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Xu
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Che
authors.forename: Guang-Chun
authors.initials: GC
authors.lastname: Wang
authors.forename: Jun-Hua
authors.initials: JH
authors.lastname: Zheng
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D053040:Nephrolithiasis / Q000150:complications* / Q000473:pathology* / Q000628:therapy; D009403:Nephrostomy, Percutaneous; D051879:Twist-Related Protein 1 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015820:Cadherins; D051879:Twist-Related Protein 1; D003404:Creatinine