Temporal Induction of Clusterin in Cisplatin Nephrotoxicity

John R. Silkensen, Anupam Agarwal, Karl A Nath, J. Carlos Manivel, Mark E. Rosenberg

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29 Scopus citations


Clusterin is a ubiquitous glycoprotein induced in many organs, including the kidney, at times of tissue injury and/or remodeling. It is speculated in this study that clusterin preserves cell interactions that are otherwise perturbed by renal insults. The purpose of this study was to examine clusterin expression after cisplatin nephrotoxicity, a model characterized by a delayed time course of injury and a well-defined site of that injury (proximal tubule). Sprague-Dawley rats were treated with intravenous cisplatin (6 mg/kg) or vehicle. Serum creatinine concentrations were measured and kidneys harvested at 1, 2, and 5 days. Marked induction of clusterin mRNA was seen only at 5 days, a time when serum creatinine concentration was the highest. Histology of kidney tissue 5 days after cisplatin administration revealed marked tubular necrosis localized to the outer stripe of the outer medulla, a region rich in proximal tubules. Immunohistochemistry and in situ hybridization at 5 days demonstrated clusterin primarily in the inner stripe of the outer medulla. In conclusion, expression of clusterin follows renal injury with cisplatin at a time corresponding to the morphologic evidence of tubular necrosis and cell detachment; quite surprisingly, such expression occurs at a site distant from the primary injury.


ASJC Scopus subject areas

  • Nephrology

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Silkensen, J. R., Agarwal, A., Nath, K. A., Manivel, J. C., & Rosenberg, M. E. (1997). Temporal Induction of Clusterin in Cisplatin Nephrotoxicity. Journal of the American Society of Nephrology, 8(2), 302-305.