Intragraft tubular vimentin and CD44 expression correlate with long-term renal allograft function and interstitial fibrosis and tubular atrophy.
BACKGROUND
Development of interstitial fibrosis and tubular atrophy (IF/TA) is the main histologic feature involved in renal allograft deterioration. The aim of this study was to validate whether de novo tubular expression of CD44 (transmembrane glycoprotein) and vimentin (mesenchymal cell marker), both involved in renal fibrosis, can operate as surrogate markers for late IF/TA and renal function. Furthermore, we wanted to establish the interrater reproducibility for the scoring system, which can be a problem in histologic assessments.


METHODS
Six-month protocol renal allograft biopsies (n=30 for matching 12 months estimated glomerular filtration rate (eGFR) from which 20 matched the 12-month protocol biopsy) were immunostained for CD44 and vimentin, semiquantitatively scored by three observers of two centers, and correlated with IF/TA and eGFR at 12 months.


RESULTS
The interobserver agreement was excellent for CD44 (Kendall's W-coefficient: 0.69; P<0.001) and vimentin (Kendall's W-coefficient: 0.79; P<0.001). CD44 and vimentin expression at 6 months were significantly correlated with IF/TA (rho=0.481 for CD44 and rho=0.619 for vimentin) and eGFR (rho=-0.569 for CD44 and rho=-0.376 for vimentin) at 12 months.


CONCLUSIONS
Summarizing, de novo tubular expression of CD44 and vimentin can function as surrogate marker for IF/TA and eGFR at 12 months. Further area under receiver operator characteristic curve analysis has to establish the predictive value for both biomarkers.
Kers
Jesper
J
Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands. j.kers@amc.uva.nl
Xu-Dubois
Yi-Chun
YC
Rondeau
Eric
E
Claessen
Nike
N
Idu
Mirza M
MM
Roelofs
Joris J T H
JJ
Bemelman
Fréderike J
FJ
ten Berge
Ineke J M
IJ
Florquin
Sandrine
S
D000328:Adult; D000911:Antibodies, Monoclonal / Q000097:blood; D001284:Atrophy; D001706:Biopsy; D005260:Female; D005355:Fibrosis / Q000473:pathology; D005919:Glomerular Filtration Rate; D006085:Graft Survival; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000276:immunology; D007150:Immunohistochemistry / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000473:pathology / Q000502:physiology*; D007684:Kidney Tubules / Q000473:pathology* / Q000502:physiology*; D008297:Male; D011183:Postoperative Complications / Q000097:blood / Q000473:pathology; D011446:Prospective Studies; D014184:Transplantation, Homologous / Q000502:physiology*; D014746:Vimentin / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
D000911:Antibodies, Monoclonal; D018960:Hyaluronan Receptors; D007166:Immunosuppressive Agents; D014746:Vimentin