Injured Proximal Tubular Epithelium Can Dedifferentiate into Vimentin Positive Cells in Human Kidneys
Lindsay Williams, Michele T Rooney, Xu Zeng, Wei Li, Ping L Zhang. William Beaumont Health System, Royal Oak, MI; Bostwick Laboratories, Inc., Orlando, FL
Background: Injured proximal tubules have been shown to dedifferentiate into cells which express vimentin in animal models. However, the dedifferentiation capacity of injured proximal tubules in human kidneys remains unknown. In this study, we compared the immunohistochemical expression of kidney injury molecule-1 (KIM-1), a specific marker of proximal tubular injury, with expression of vimentin in renal allograft biopsies with acute tubular injury (ATI).
Design: Human renal tissue from either indicated allograft biopsies with ATI (n=26, group 2) or protocol allograft biopsies (n=17, group 1) was stained with KIM-1 (AKG7 monoclonal antibody, provided by Dr. Joseph V. Bonventre, BWH, Boston, MA) and vimentin (monoclonal antibody, Dako). KIM-1 and vimentin stains were graded from 0 to 3+ in the proximal tubular epithelium. Serum creatinine, KIM-1 and vimentin scores were statistically evaluated by linear regression analysis.
Results: Serum creatinine, KIM-1 scores and vimentin scores were all significantly higher in the ATI cases (3.655±0.388 mg/dL, 1.962±0.188 arbitrary units (AU), and 1.269±0.219 AU) than in control protocol biopsies (1.318±0.061 mg/dL, 0.324±0.095 AU, and 0.000±0.000 AU). Overall (n= 43), serum creatinine was significantly correlated with KIM-1 expression (R=0.746, P=0.0001) and vimentin (R=0.659, P=0.0001). There was also a significant correlation between KIM-1 scores and vimentin scores. In group 2, 61% (17/26) of cases had vimentin expression which was one score level weaker than the respective KIM-1 expression (e.g. vimentin 2+ with KIM-1 3+), whereas 26% cases showed equal levels of expression for both biomarkers.
Conclusions: Injured proximal tubules in humans also undergo vimentin dedifferentiation as shown in animal models. Vimentin dedifferentiation occurred essentially parallel to the tubular injury, confirmed by the correlation of positive staining with KIM-1 and vimentin. However, slightly delayed vimentin expression, demonstrated by weaker vimentin scores relative to the respective KIM-1, raises the possibility that strong vimentin dedifferentiation in the tubular epithelium may indicate a non-reversible tubular injury.
Category: Kidney (does not include tumors)
Monday, March 4, 2013 1:00 PM
Poster Session II # 256, Monday Afternoon