title: Fas expression in nephrectomized, non-cancerous specimens predicts post-nephrectomy chronic kidney disease progression in patients with renal and upper urinary tract malignancies.
abstract: OBJECTIVE
  Despite the surgical curability of renal cell carcinoma (RCC) and upper urinary tract urothelial carcinoma (UUT-UC), post-nephrectomy chronic kidney disease (CKD) continues to be a cause of concern. We investigated the correlation between the expression of apoptotic regulatory molecules in the nephrectomized, noncancerous cortex, as well as CKD progression and CKD-related mortality.
  
  
  METHODS
  Fas and Bcl-2 mRNA and protein expression in surgically resected specimens from 100 patients with RCC and UUT-UC were determined. The estimated glomerular filtration rates (eGFR) were determined sequentially before surgery and up to 5 years after surgery. The relationships between CKD progression, the expression of these molecules in the renal cortex, and the clinical characteristics were analyzed.
  
  
  RESULTS
  The mean 1-year postoperative percent eGFR decrease was 30.2 (Standard deviation [SD]: 15.2). The 1-year postoperative percent eGFR decrease greater than the approximate value of mean ± SD (45) was categorized as severe renal functional deterioration (SRFD). Glomerular Fas protein expression and a Fas/β-actin mRNA ratio >0.3 were independent predictors for SRFD. Significantly increased mortality rates due to cardiovascular events were indicated by glomerular Fas protein expression, Fas mRNA levels >0.3, and SRFD. No significant change in Bcl-2 levels was observed.
  
  
  CONCLUSIONS
  This study is the first report to demonstrate the significance of Fas expression in the nephrectomized normal cortex as a predictor of post-nephrectomy CKD progression. The results from nephrectomized kidney showed that the natural course of renal function in the remaining kidney may be affected not only by Fas-induced glomerular cell apoptosis but also by the total amount of Fas mRNA in cortical cells.
authors.affiliation: Division of Urology, Department of Surgery, Tottori University Faculty of Medicine, Yonago, Japan. Electronic address: sejimat@grape.med.tottori-u.ac.jp.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Sejima
authors.forename: Hideto
authors.initials: H
authors.lastname: Iwamoto
authors.forename: Shuichi
authors.initials: S
authors.lastname: Morizane
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hinata
authors.forename: Akihisa
authors.initials: A
authors.lastname: Yao
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Isoyama
authors.forename: Motoaki
authors.initials: M
authors.lastname: Saito
authors.forename: Takashi
authors.initials: T
authors.lastname: Amisaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takenaka
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005919:Glomerular Filtration Rate; D006801:Humans; D007150:Immunohistochemistry; D007672:Kidney Cortex / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000601:surgery*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy / Q000379:methods; D011237:Predictive Value of Tests; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014551:Urinary Tract / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D014571:Urologic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000601:surgery*; D019014:fas Receptor / Q000235:genetics* / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor