P53 protein is a reliable marker in identification of renal tubular injury

Acute tubular necrosis (ATN) ranges from minimal histologic changes to overt necrotic tubules. Although histologic changes on routine stained sections can be seen in many ATN cases, they may be subtle in some cases. In some cases, electron microscopy may reveal more reliable findings to support a diagnosis of ATN. Thus, a molecular marker to confirm acute tubular damage and to differentiate mild from moderate tubular injury could provide more reliable detection of ATN at the light microscopic level. In this study, sections from native and transplant renal biopsies with the diagnosis of ATN were stained immunohistochemically for p53, an upstream marker for DNA damage, and compared with donor baseline biopsies as controls. The transplant and native ATN kidney groups had significantly higher numbers of p53 nuclear staining in renal tubular epithelium (transplant ATN: 4.58 +/- 1.51/mm(2), n = 18, and native ATN: 6.12 +/- 1.99/mm(2), n = 13) than the donor baseline group (1.09 +/- 0.51/mm(2), n = 16) or controls-normal renal parenchyma away from tumors (0.029 +/- 0.017). Cases with moderate ATN changes showed significantly increased p53 tubular staining (transplant ATN: 9.20 +/- 2.59/mm(2), n = 8, and native ATN: 14.3 +/- 1.88/mm(2), n = 5) when compared with the mild ATN cases (transplant ATN: 0.87 +/- 0.30/mm(2), n = 10, and native ATN: 1.01 +/- 0.39/mm(2); n = 8). In summary, there was direct correlation between nuclear p53 staining and morphologic changes seen microscopically and ultrastructurally, suggesting that p53 can be used as a reliable marker of cellular damage to aid in the diagnosis of ATN.