Pioglitazone Attenuates Cystic Burden in the PCK Rodent Model of Polycystic Kidney Disease

Abstract

Polycystic kidney disease (PKD) is a genetic disorder characterized by growth of fluid-filled cysts predominately in kidney tubules and liver bile ducts. Currently, the clinical management of PKD is limited to cyst aspiration, surgical resection or organ transplantation. Based on an observation that PPARγagonists such as pioglitazone and rosiglitazone decrease mRNA levels of aCl−transport protein, CFTR (cystic fibrosis transmembrane conductance regulator), and theCl−secretory response to vasopressin in cultured renal cells, it is hypothesized that PPARγagonists will inhibit cyst growth. The current studies show that a 7- or 14-week pioglitazone feeding regimen inhibits renal and hepatic bile duct cyst growth in the PCK rat, a rodent model orthologous to human PKD. These studies provide proof of concept for the mechanism of action of the PPARγagonists and suggest that this class of drugs may be effective in controlling both renal and hepatic cyst growth and fibrosis in PKD.