title: Noninvasive analyses of kidney injury molecule-1 messenger RNA in kidney transplant recipients with graft dysfunction.
abstract: BACKGROUND
  Kidney graft fibrosis is a major factor related to chronic loss of kidney function. At present, the finding of fibrosis depends on the analysis of tissue in the renal biopsy, which has important limitations. In this study, we evaluated the messenger mRNA transcription and gene expression of kidney injury molecule-1 (KIM-1) in kidney tissue and in urinary sediment cells of kidney transplant patients with graft dysfunction aiming at the development of techniques that may allow the noninvasive diagnosis of interstitral fibrosis/tubular atrophy (IF/TA).
  
  
  METHODS
  RNA extracted from cells in tissue and urine of 77 renal transplant patients whose biopsies were classified according to the Banff scheme-2007. Four diagnostic groups were established: (1) acute tubular necrosis (n = 9); (2) acute rejection (n = 49); (3) acute calcineurin inhibitors nephrotoxicity (n = 10); and (4) interstitial fibrosis and tubular atrophy (IFTA, n = 29). Tissue and urine cell RNA was amplified and quantification were made by real-time polymerase chain reactron. Data from the quantification of gene expression are presented as median and 25th to 75th percentiles.
  
  
  RESULTS
  Messenger RNA levels of the KIM-1 gene were higher in the biopsies (26.17; 3.38-294.53) and urinary sediment cells (0.09; 0-5.81) of the patients classified as having IF/TA as compared with all others groups. A significant correlation between gene expression in samples of urine and tissue cells was found (P < .01).
  
  
  CONCLUSIONS
  These initial data suggests that KIM-1 gene mRNA quantification can be used as a noninvasive biomarker of IF/TA.
authors.affiliation: Post-Graduate Medical Sciences Program, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: A L
authors.initials: AL
authors.lastname: Nogare
authors.forename: T
authors.initials: T
authors.lastname: Dalpiaz
authors.forename: F J V
authors.initials: FJ
authors.lastname: Veronese
authors.forename: L F
authors.initials: LF
authors.lastname: Gonçalves
authors.forename: R C
authors.initials: RC
authors.lastname: Manfro
mesh_terms: D001284:Atrophy; D001706:Biopsy; D005260:Female; D005355:Fibrosis; D005819:Genetic Markers; D006084:Graft Rejection / Q000235:genetics* / Q000473:pathology / Q000652:urine; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007668:Kidney / Q000737:chemistry* / Q000187:drug effects / Q000473:pathology / Q000601:surgery*; D007674:Kidney Diseases / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology / Q000652:urine; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000652:urine; D009336:Necrosis; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis* / Q000652:urine; D060888:Real-Time Polymerase Chain Reaction; D011991:Receptors, Virus / Q000235:genetics*; D016896:Treatment Outcome; D016482:Urinalysis
chemical_list: D005819:Genetic Markers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011991:Receptors, Virus