PPARγ agonist inhibition of cyst growth in the W‐WPK rat model of polycystic kidney disease assessed by CT scans

Abstract

Polycystic kidney diseases (PKD) are genetic disorders characterized by fluid‐filled cysts in kidney tubules and liver bile ducts. Cyst enlargement is due, at least in part, to Cl− secretion via the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel. Previous studies demonstrated that PPARγ agonists, pioglitazone and rosiglitazone, insulin sensitizing drugs used to treat diabetes, inhibit Cl− secretion in collecting duct cells via decreased CFTR synthesis. Our preclinical studies showed that pioglitazone and low (0.04 mg/kg BW) dose rosiglitazone inhibited cyst growth in the PCK rat model of PKD. The current study was designed to study the effect of the agonists in an alternative PDK model and to determine if CT scans could be used to track the progress of disease and drug therapy. W‐WPK rats, a rapidly progressing model, were fed a diet containing pioglitazone (20 and 2 mg/kg BW) from day 5 to 18. In agreement with previous studies, the lower dose was the most effective in reducing cyst growth. The CT scans proved to be effective in determining the progress of the disease and yielded results that correlated well with post‐sacrifice analyses. Funding: CTSI grant ‐ IUSM