title: Tubulointerstitial expression and urinary excretion of connective tissue growth factor 3 months after renal transplantation predict interstitial fibrosis and tubular atrophy at 5 years in a retrospective cohort analysis.
abstract: Connective tissue growth factor (CTGF) is an important mediator of renal allograft fibrosis, and urinary CTGF (CTGFu) levels correlate with the development of human allograft interstitial fibrosis. We evaluated the predictive value of CTGF protein expression in 160 kidney transplant recipients with paired protocol biopsies at 3 months and 5 years after transplantation. At month 3 and year 1, CTGFu was measured using ELISA, and biopsies were immunohistochemically stained for CTGF, with semiquantitative scoring of tubulointerstitial CTGF-positive area (CTGFti). Predictors of interstitial fibrosis and tubular atrophy (IF/TA) severity at 5 years were donor age [OR 1.05 (1.02-1.08), P = 0.001], female donor [OR 0.40 (0.18-0.90), P = 0.026], induction therapy [OR 2.76 (1.10-6.89), P = 0.030], and CTGFti >10% at month 3 [OR 2.72 (1.20-6.15), P = 0.016]. In subgroups of patients with little histologic damage at 3 months [either ci score 0 (n = 119), IF/TA score ≤1 (n = 123), or absence of IF/TA, interstitial inflammation, and tubulitis (n = 45)], consistent predictors of progression of chronic histologic damage by 5 years were donor age, induction therapy, CTGFti >10%, and CTGFu. These results suggest that, even in patients with favorable histology at 3 months, significant CTGF expression is often present which may predict accelerated accumulation of histologic damage.
authors.affiliation: Department of Microbiology and Immunology, KU Leuven - University of Leuven, Leuven, Belgium.|Department of Nephrology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Thomas
authors.identifier: http://orcid.org/0000-0001-5712-6294
authors.initials: T
authors.lastname: Vanhove
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Nephrology, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kinashi
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Tri Q
authors.initials: TQ
authors.lastname: Nguyen
authors.affiliation: Department of Microbiology and Immunology, KU Leuven - University of Leuven, Leuven, Belgium.|Department of Nephrology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Christoph
authors.initials: C
authors.lastname: Metalidis
authors.affiliation: Clinical Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Poesen
authors.affiliation: Department of Microbiology and Immunology, KU Leuven - University of Leuven, Leuven, Belgium.|Department of Nephrology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Maarten
authors.initials: M
authors.lastname: Naesens
authors.affiliation: Department of Imaging and Pathology, KU Leuven - University of Leuven, Leuven, Belgium.|Department of Pathology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Lerut
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Roel
authors.initials: R
authors.lastname: Goldschmeding
authors.affiliation: Department of Microbiology and Immunology, KU Leuven - University of Leuven, Leuven, Belgium.|Department of Nephrology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Dirk R J
authors.initials: DRJ
authors.lastname: Kuypers
mesh_terms: D000328:Adult; D001284:Atrophy; D015331:Cohort Studies; D055513:Connective Tissue Growth Factor / Q000378:metabolism* / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005355:Fibrosis; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D007674:Kidney Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: C526317:CCN2 protein, human; D055513:Connective Tissue Growth Factor
keywords: connective tissue growth factor; fibrosis; kidney transplant