title: Relation of urinary gene expression of epithelial-mesenchymal transition markers with initial events and 1-year kidney graft function.
abstract: BACKGROUND
  Renal dysfunction due to acute rejection (AR), acute tubular necrosis, or calcineurin inhibitors toxicity is related to development of interstitial fibrosis/tubular atrophy (IF/TA) and graft survival. Determination of serum creatinine (sCr) displays poor sensitivity as a marker for early detection of graft dysfunction. Kidney biopsy is an accurate but invasive procedure for the diagnosis. The levels of urinary mRNA of genes that regulate epithelial-mesenchymal transition (EMT) can reflect early damage and detect the development of IF/TA. Repeated studies of these genes can provide noninvasive information about the evolution of the graft, facilitating early diagnosis and treatment.
  
  
  OBJECTIVE
  To analyze the relationships between early and 1-year graft evolution in relation to gene expression of EMT biomarkers.
  
  
  METHODS
  Seventy-one kidney transplant recipients were monitored during 1 year recording analytical, clinical, and histological (if available) data. We determined RNA gene expression of EMT, angiotensinogen, E-cadherin, N-cadherin, transforming growth factor (TGF) beta and bone morphogenetic patients 7 (BMP7).
  
  
  RESULTS
  At 3 months, angiotensinogen (mean [standard deviation]), (2.42 [.66] versus 8.58 [3.24]; P = .017) and N-cadherin (0.59 [0.26] versus 3.15 [1.35]; P = .016) discriminate a good evolution from AR episodes BMP-7 discriminated a good evolution versus AR (0.72 [0.29] versus 4.53 [2.23]; P = .006) and delayed graft function versus AR (1.14 [0.79] versus 4.53 [2.23]; P = .049). After 1 year, the ratio TGF-beta/BMP7 discriminated patients with an sCr > 1.5 mg/dL (6614.6 [1063.6] versus 3378.7 [1019]; P = .034). There was a positive correlation between urinary and tissue TGF-beta [r = 59; P = .003].
  
  
  CONCLUSIONS
  The expression of studied genes reverting EMT at 3 months postransplantation showed differences in initial graft evolution. At 1 year, the TGF-beta/BMP7 ratio suggested activation of EMT, possible early marker of renal dysfunction.
authors.affiliation: Nephrology Department, Marques de Valdecilla Hospital, University of Cantabria, Institute for Investigation "Marques de Valdecilla" (IFIMAV), Santander, Cantabria, Spain. alamillo@humv.es
authors.forename: C
authors.initials: C
authors.lastname: Gomez-Alamillo
authors.forename: M A
authors.initials: MA
authors.lastname: Ramos-Barron
authors.forename: A
authors.initials: A
authors.lastname: Benito-Hernandez
authors.forename: E
authors.initials: E
authors.lastname: Rodrigo
authors.forename: J C
authors.initials: JC
authors.lastname: Ruiz
authors.forename: C
authors.initials: C
authors.lastname: Agüeros
authors.forename: M
authors.initials: M
authors.lastname: Sanchez
authors.forename: M
authors.initials: M
authors.lastname: Arias
mesh_terms: D000808:Angiotensinogen / Q000235:genetics; D015703:Antigens, CD / Q000235:genetics; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D003404:Creatinine / Q000097:blood; D051799:Delayed Graft Function / Q000209:etiology / Q000235:genetics / Q000652:urine; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005355:Fibrosis; D005786:Gene Expression Regulation; D005819:Genetic Markers; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000652:urine; D016030:Kidney Transplantation / Q000009:adverse effects; D012333:RNA, Messenger / Q000652:urine; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D015703:Antigens, CD; C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; C513384:CDH1 protein, human; C050361:CDH2 protein, human; D015820:Cadherins; D005819:Genetic Markers; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D000808:Angiotensinogen; D003404:Creatinine