title: Kidney injury molecule-1 expression in human kidney transplants with interstitial fibrosis and tubular atrophy.
abstract: BACKGROUND
  Kidney injury molecule-1 (KIM-1) is expressed in tubular epithelial cells after injury and may have a role in the development of renal graft fibrosis. In this study we evaluated the molecular and protein expressions of KIM-1 in dysfunctional allografts and also mRNA KIM-1 expression in urine as potential biomarkers of graft fibrosis.
  
  
  METHODS
  Protein and mRNA levels in renal tissue and urinary sediment cells of 69 kidney transplant recipients that undertook for-cause graft biopsies were evaluated by immunohistochemistry and real-time polymerase chain reaction. The histopathology was classified according to the 2007 Banff schema.
  
  
  RESULTS
  KIM-1 protein expression was increased in biopsies with interstitial fibrosis and tubular atrophy (IF/TA) compared with biopsies showing acute calcineurin inhibitor nephrotoxicity (CIN) (P <0.05). Kidney tissue KIM-1 mRNA signaling (in) was increased in biopsies with IF/TA compared with all other groups (P <0.05). In the urine cells KIM-1 mRNA was also increased in patients with IF/TA compared with patients with acute CIN (P <0.05). Significant correlations were found between KIM-1 protein and mRNA levels in tissue, between mRNA expressions in tissue and urine and between protein tissue expression and gene expression in the urine.
  
  
  CONCLUSIONS
  KIM-1 seems to be a marker of kidney graft fibrosis. Urinary KIM-1 mRNA may become a useful non-invasive biomarker of the injuries that can trigger intra-graft fibrotic processes, such as interstitial fibrosis and tubular atrophy.
authors.affiliation: Post-Graduate Medical Sciences Program, School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. alnogare@gmail.com.
authors.forename: Aline Lima
authors.initials: AL
authors.lastname: Nogare
authors.affiliation: Post-Graduate Medical Sciences Program, School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. fjvveronese@gmail.com.|Renal Transplant Unit, Division of Nephrology, Hospital de Clínicas de Porto Alegre, Post-Graduate Medical Sciences Program, School of Medicine, Federal University of Rio Grande do Sul 2350, Ramiro Barcelos St. Room 2030, Zip Code: 90035-903, Porto Alegre, RS, Brazil. fjvveronese@gmail.com.
authors.forename: Francisco Veríssimo
authors.initials: FV
authors.lastname: Veronese
authors.affiliation: Post-Graduate Medical Sciences Program, School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. virna.carpio@gmail.com.
authors.forename: Virna Nowotny
authors.initials: VN
authors.lastname: Carpio
authors.affiliation: Renal Transplant Unit, Division of Nephrology, Hospital de Clínicas de Porto Alegre, Post-Graduate Medical Sciences Program, School of Medicine, Federal University of Rio Grande do Sul 2350, Ramiro Barcelos St. Room 2030, Zip Code: 90035-903, Porto Alegre, RS, Brazil. rosangelamontenegro@yahoo.com.br.
authors.forename: Rosangela Munhoz
authors.initials: RM
authors.lastname: Montenegro
authors.affiliation: Renal Transplant Unit, Division of Nephrology, Hospital de Clínicas de Porto Alegre, Post-Graduate Medical Sciences Program, School of Medicine, Federal University of Rio Grande do Sul 2350, Ramiro Barcelos St. Room 2030, Zip Code: 90035-903, Porto Alegre, RS, Brazil. josealbertopedroso@gmail.com.
authors.forename: José Alberto
authors.initials: JA
authors.lastname: Pedroso
authors.affiliation: Division of Pathology, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil. lfp.voy@terra.com.br.
authors.forename: Karla Laís
authors.initials: KL
authors.lastname: Pegas
authors.affiliation: Post-Graduate Medical Sciences Program, School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. luisfelipe@maededeus.com.br.|Renal Transplant Unit, Division of Nephrology, Hospital de Clínicas de Porto Alegre, Post-Graduate Medical Sciences Program, School of Medicine, Federal University of Rio Grande do Sul 2350, Ramiro Barcelos St. Room 2030, Zip Code: 90035-903, Porto Alegre, RS, Brazil. luisfelipe@maededeus.com.br.
authors.forename: Luiz Felipe
authors.initials: LF
authors.lastname: Gonçalves
authors.affiliation: Post-Graduate Medical Sciences Program, School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. rmanfro@hcpa.ufrgs.br.|Renal Transplant Unit, Division of Nephrology, Hospital de Clínicas de Porto Alegre, Post-Graduate Medical Sciences Program, School of Medicine, Federal University of Rio Grande do Sul 2350, Ramiro Barcelos St. Room 2030, Zip Code: 90035-903, Porto Alegre, RS, Brazil. rmanfro@hcpa.ufrgs.br.
authors.forename: Roberto Ceratti
authors.initials: RC
authors.lastname: Manfro
mesh_terms: D000328:Adult; D064591:Allografts; D001284:Atrophy / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D001707:Biopsy, Needle; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000235:genetics* / Q000473:pathology; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007150:Immunohistochemistry; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000379:methods; D007684:Kidney Tubules / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000473:pathology; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000652:urine*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D011991:Receptors, Virus / Q000235:genetics*; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011991:Receptors, Virus