title: Urinary connective tissue growth factor increases far earlier than histopathological damage and functional deterioration in early chronic renal allograft injury.
abstract: OBJECTIVE
  To date, serum biochemistry examination and routine biopsy are the most commonly used methods to assess renal function after allogenic kidney transplantation. Connective tissue growth factor (CTGF) has been considered as a biomarker of chronic renal allograft injury characterized by tubular atrophy and interstitial fibrosis (TA/IF). This study explored the potential value of urinary CTGF as an early predictor of TA/IF using a rat model.
  
  
  METHODS
  A Fisher to Lewis allogenic rat kidney transplant model was established and the recipients were killed at weeks 4, 8 and 12 post-transplantation. TA/IF was graded based on Banff Schema 1997. The location and expression of CTGF mRNA were detected by oligonucleotide-primed in situ DNA synthesis and quantitative polymerase chain reaction. CTGF protein expression was examined with immunohistochemistry and immunoblotting. Urinary CTGF concentration was measured by enzyme-linked immunosorbent assay. The correlation between urinary CTGF concentration and serum creatinine (SCr) and Banff score was analysed statistically.
  
  
  RESULTS
  Typical morphological changes including TA/IF in allograft appeared at week 8 and became very severe at week 12 post-transplantation. CTGF expression in epithelium was up-regulated early and urinary CTGF was markedly elevated from week 4. SCr in recipients was stable before week 8 but increased tremendously at week 12. Urinary CTGF concentration was positively correlated with SCr and degree of interstitial fibrosis.
  
  
  CONCLUSIONS
  Urinary CTGF increases earlier than the appearance of biochemical abnormalities and pathological changes. Measurement of urinary CTGF may offer a potential non-invasive strategy to predict the early onset of chronic renal allograft injury.
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, PR China.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Shi
authors.forename: Zhidan
authors.initials: Z
authors.lastname: Tu
authors.forename: Ji
authors.initials: J
authors.lastname: Bao
authors.forename: Huaiqiang
authors.initials: H
authors.lastname: Sun
authors.forename: We
authors.initials: W
authors.lastname: Wang
authors.forename: Guangheng
authors.initials: G
authors.lastname: Luo
authors.forename: Shengfu
authors.initials: S
authors.lastname: Li
authors.forename: Youping
authors.initials: Y
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Bu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000652:urine; D015153:Blotting, Western; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000652:urine*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D015870:Gene Expression; D006084:Graft Rejection / Q000235:genetics / Q000473:pathology / Q000652:urine*; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology*; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000473:pathology / Q000652:urine*; D016030:Kidney Transplantation / Q000473:pathology*; D008297:Male; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D055513:Connective Tissue Growth Factor