Stem/Progenitor Cell Marker CD133 Identifies Glomerular and Tubular Injury in Human Renal Biopsies
Ping L Zhang, Michele T Rooney, Sharon K Hicks, Wei Li, Guillermo A Herrera. William Beaumont Hospital, Royal Oak, MI; Bostwick Laboratories, Orlando, FL
Background: CD133, a stem/progenitor cell marker, expresses in parietal epithelial cells (PEC) of normal glomeruli and crescentic glomerulonephritis by immunofluorescent methods. This study was to investigate immunohistochemical (IHC) expression of CD133 in glomerular and tubules injury from renal biopsies.
Design: There were 16 control unremarkable renal sections (from nephrectomy for renal tumors). The acute kidney injury (AKI) group was composed of 63 native renal biopsies, with 9 primary acute tubular necrosis (ATN), 5 tubulointerstitial disease, 13 primary crescentic glomerulonephritis (GN), 14 thrombotic microangiopathy, 9 collapsing GN/HIV nephropathy, 6 biopsies with variants of monoclonal light chain nephropathy and 8 pediatric renal biopsies. They were all immunohistochemically stained for CD133 (monoclonal AC133 antibody at 1:50 dilution and a polyclonal CD133 antibody 1:500).
Results: Stains using two types of CD133 antibodies demonstrated a similar pattern of staining in normal and injured renal tissue. CD133 staining in normal PEC and crescents was confirmed as reported. In the normal kidney, there was minimal or rare CD133 staining in tubular epithelium. But in the injured proximal tubules, a gradient CD133 expression along luminal membranes was present from 1+ to 3+ (63 out of 63 cases), depending on the extent of injury. With AKI, many distal-nephron tubular cells expressed CD133 along luminal membranes as well. Double stains for CD133 (brown membranous stain) and p53 (pink nuclear stain) showed co-expression in injured renal tubules (Panel B), when compared to control (Panel A).
Furthermore, the tubular expression of CD133 was significantly correlated with serum creatinine levels.
Conclusions: We confirmed CD133 expression in normal PEC and crescents of CGN as shown previously. Importantly, the tubular upregulation of CD133 along luminal membranes implies that renal "progenitor-like" cells exist along tubular epithelium for tubular regeneration and the tubular injury can significantly contribute to AKI even in conventional "glomerular disorders". Finally, the IHC staining for CD133 can be used for confirming lesions in glomeruli and renal tubules of renal biopsies, better than any marker we tested.
Category: Kidney (does not include tumors)
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 267, Wednesday Afternoon