Genesis of renal cysts is associated with clusterin expression in experimental cystic disease

Phenol II is a cystogenic chemical that rapidly induces renal cysts, which regress after drug withdrawal. Cyst formation in this model parallels changes in the tubular basement membrane. Clusterin is a potent cohesive factor induced in states of tissue remodeling. The purpose of this study was to determine if renal clusterin was increased in the Phenol II model and to define the time course and distribution of its induction. Male Sprague-Dawley rats were given, by daily gavage, Phenol II (1.2 mg/kg per day) or vehicle (control). The kidneys were harvested after 1, 2, or 4 days of Phenol II treatment or 3 or 7 days after drug withdrawal. An increase in immunoreactive clusterin was seen in the kidneys of Phenol II-treated rats but not in controls. The appearance of clusterin followed a time course similar to that for cyst formation, with expression confined to the epithelial lining and intratubular casts of dilated or cystic tubules. After Phenol II withdrawal, renal cysts regressed and clusterin staining disappeared. The development of cysts was associated with an increase in clusterin mRNA that decreased after drug withdrawal. In conclusion, a marked, yet reversible induction of clusterin occurred in chemically induced polycystic kidney disease. The function of clusterin in this setting remains enigmatic.