Although
pioglitazone, a
PPAR-gamma (
peroxisome-proliferator-activated receptor-gamma) agonist, has been shown to prolong survival in two rapidly progressive pkd1 (
polycystic kidney disease 1)-knockout mice models through disparate mechanisms, these studies lacked data on therapeutic potential and long-term safety because of a short observation period. In the present study, we have used another potent
PPAR-gamma agonist,
rosiglitazone, to treat Han:SPRD rats, a slowly progressive
ADPKD (autosomal dominant PKD) animal model, and confirmed that short-term treatment was able to delay the progression of kidney
cysts and protect renal function, which may relate to down-regulating the abnormally activated
beta-catenin signalling pathway and its anti-inflammatory and anti-
fibrosis effects. Long-term administration significantly prolonged the survival of Han:SPRD rats. Moreover,
early therapy in rats with normal renal function had a better outcome than delayed
therapy, while initiating
therapy in rats with mild impaired renal function still protected renal function. The efficacy of
rosiglitazone depended on continuous
drug administration; withdrawal of the
drug caused accelerated deterioration of renal function in effectively treated rats and shortened their survival to an untreated state. Long-term administration led to cardiac enlargement, probably due to
rosiglitazone-mediated
sodium re-absorption. In conclusion, these results indicate that
rosiglitazone was able to effectively delay the progression of
kidney disease and protect renal function in Han:SPRD rats, but its adverse effect of inducing cardiac enlargement should also be monitored closely.