期刊
KIDNEY & BLOOD PRESSURE RESEARCH
卷 30, 期 4, 页码 253-259出版社
KARGER
DOI: 10.1159/000104818
关键词
polycystic kidney disease; everolimus; mTOR; Han : SPRD rat
Background/ Aims: Rapamycin inhibits cyst growth in polycystic kidney disease by targeting the mammalian target of rapamycin ( mTOR). To determine if this is a class effect of the mTOR inhibitors, we examined the effect of everolimus, the analogue of rapamycin, on disease progression in the Han: SPRD rat model of polycystic kidney disease. Methods: Four- week- old male heterozygous cystic ( Cy/+) and wildtype normal (+/+) Han: SPRD rats were administered everolimus or vehicle ( 3 mg/ kg/ day) by gavage for 5 weeks. Kidney function and whole- blood trough levels of everolimus were monitored. After treatment kidney weight and cyst volume density were assessed. Tubule epithelial cell proliferation was assessed by BrdU staining. Results: Everolimus trough levels between 5 and 7 mu g/ l were sufficient to significantly reduce kidney and cyst volume density by approximately 50 and 40%, respectively. The steady decrease of kidney function in Cy/+ rats was reduced by 30% compared with vehicletreated Cy/+ rats. Everolimus treatment markedly reduced the number of 5- bromo- 2- deoxyuridine- labeled nuclei in cyst epithelia. Body weight gain and kidney function were impaired in everolimus- treated wild- type rats. Conclusion: Moderate dosage of everolimus inhibits cystogenesis in Han: SPRD rats. The inhibitory effect of everolimus appears to represent a class effect of mTOR inhibitors.
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