Although pioglitazone, a PPAR-γ (peroxisome-proliferator-activated receptor-γ) 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-γ 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 β-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.
Rosiglitazone attenuates development of polycystic kidney disease and prolongs survival in Han:SPRD rats
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Bing Dai, Yawei Liu, Changlin Mei, Lili Fu, Xishan Xiong, Yan Zhang, Xuefei Shen, Zhenhao Hua; Rosiglitazone attenuates development of polycystic kidney disease and prolongs survival in Han:SPRD rats. Clin Sci (Lond) 1 October 2010; 119 (8): 323–333. doi: https://doi.org/10.1042/CS20100113
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