title: Histopathology and biomarkers in prediction of renal function in children after kidney transplantation.
abstract: BACKGROUND
  Early detection of chronic allograft injury is a major challenge after kidney transplantation (RTx) in adults and children. We correlated the expression of four immunohistochemical biomarkers, P-selectin glycoprotein ligand-1 (PSGL-1), vimentin, α-smooth muscle actin (α-SMA) and collagen IV, to the kidney graft histology and function in pediatric RTx patients.
  
  
  METHODS
  We analyzed the histopathology and immunohistochemical stainings of 165 biopsies from 56 patients. Histopathology was scored according to Banff '05 classification and biomarker expression semiquantitatively. Glomerular filtration rate (GFR) was measured annually by (51)Cr-EDTA clearance.
  
  
  RESULTS
  In protocol biopsies, the expression of all four biomarkers correlated with the interstitial fibrosis and tubular atrophy (IF/TA) changes, which increased during the first 36months after RTx. At the time of 18month biopsy, we observed the deterioration of GFR in patients with high (≥2) IF/TA score (50 vs. 68ml/min/1.73m(2), p=0.004) or collagen IV expression (45 vs. 65ml/min/1.73m(2), p=0.016). Intense stainings of IF/TA, collagen IV and vimentin are also associated with poor GFR at 36 and 48months, however, the biomarker scores revealed no additional predictive value for concomitant or late GFR compared to IF/TA score. Patients with high and low biomarker expressions showed no significant differences in annual deterioration of GFR, which declined on average 2.2ml/min/1.73m(2)/year over the 7years follow-up.
  
  
  CONCLUSIONS
  Overall, the results suggest that traditional histopathology is a sufficient predictor for graft function, and the routine use of these histochemical markers as surrogates for graft function deterioration is questioned.
authors.affiliation: Department of Pediatric Nephrology and Transplantation, Children's Hospital, University of Helsinki and Helsinki University Central Hospital, PL 281, 00029 HUS, Helsinki, Finland. Electronic address: jenni.v.miettinen@helsinki.fi.
authors.forename: Jenni
authors.initials: J
authors.lastname: Miettinen
authors.affiliation: Division of Pathology and Genetics, HUSLAB, Helsinki University Central Hospital, PL 400, 00029 HUS, Helsinki, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Helin
authors.affiliation: Department of Pediatric Surgery, Children's Hospital, University of Helsinki and Helsinki University Central Hospital, PL 281, 00029 HUS, Helsinki, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Pakarinen
authors.affiliation: Department of Pediatric Nephrology and Transplantation, Children's Hospital, University of Helsinki and Helsinki University Central Hospital, PL 281, 00029 HUS, Helsinki, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Jalanko
authors.affiliation: Histocompatibility Laboratory, Finnish Red Cross Blood Service, Kivihaantie 7, 00310 Helsinki, Finland.
authors.forename: Jouni
authors.initials: J
authors.lastname: Lauronen
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000293:Adolescent; D064591:Allografts / Q000276:immunology / Q000293:injuries; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D024141:Collagen Type IV / Q000096:biosynthesis; D051799:Delayed Graft Function / Q000473:pathology*; D005260:Female; D005355:Fibrosis / Q000473:pathology*; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007223:Infant; D007668:Kidney / Q000473:pathology / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D014746:Vimentin / Q000096:biosynthesis
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D015415:Biomarkers; D024141:Collagen Type IV; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D014746:Vimentin
keywords: Biomarker; Children; Glomerular filtration rate; Kidney transplantation