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Am J Nephrol. 2009;30(5):468-73. doi: 10.1159/000242432. Epub 2009 Sep 24.

Effect of pioglitazone on survival and renal function in a mouse model of polycystic kidney disease.

Author information

1
Division of Nephrology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA.

Abstract

BACKGROUND/AIMS:

Cystic epithelia in polycystic kidney disease display features similar to malignant cells. Thiazolidinediones have been shown to have anti-neoplastic properties, therefore we tested the hypothesis that pioglitazone reduces cyst formation, improves renal function, and prolongs survival in a mouse model of polycystic kidney disease.

METHODS:

PC-Pkd1-KO mice, which have homozygous mutations of the Pkd1 gene in principal cells, were used. On the day after giving birth, mothers were fed standard mouse chow with or without pioglitazone (30 mg/kg chow). After weaning, the assigned diet was continued. At 1 month of age, blood pressure was measured and animals were sacrificed to determine kidney weight, body weight, and serum urea. Kidneys were evaluated for proliferation using Ki-67, apoptosis using TUNEL analysis, and cyst number using MRI. Survival was observed.

RESULTS:

Pioglitazone did not alter renal function, cell proliferation, apoptosis, or cyst formation in animals with polycystic kidney disease, however it did increase survival. Pioglitazone reduced blood pressure in PC-Pkd1-KO, but not in controls.

CONCLUSION:

These findings suggest that pioglitazone may have a unique antihypertensive effect in polycystic kidney disease, and that such an effect may promote improved survival.

PMID:
19776560
PMCID:
PMC2818398
DOI:
10.1159/000242432
[Indexed for MEDLINE]
Free PMC Article

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