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


CONCLUSIONS
These findings suggest that pioglitazone may have a unique antihypertensive effect in polycystic kidney disease, and that such an effect may promote improved survival.
Division of Nephrology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA.
K L
KL
Raphael
K A
KA
Strait
P K
PK
Stricklett
B C
BC
Baird
K
K
Piontek
G G
GG
Germino
D E
DE
Kohan
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D006977:Hypertension, Renal / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D000077205:Pioglitazone; D007690:Polycystic Kidney Diseases / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D050396:TRPP Cation Channels / Q000235:genetics; D045162:Thiazolidinediones / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D000077205:Pioglitazone; D050396:TRPP Cation Channels; D045162:Thiazolidinediones