Atorvastatin ameliorates tubulointerstitial fibrosis and protects renal function in chronic partial ureteral obstruction cases.
OBJECTIVE
Tubulointerstitial fibrosis, the histological feature of chronic obstructive nephropathy, is delineated in complete unilateral ureteral obstruction models. Histological changes during chronic partial ureteral obstruction are not well studied. We describe changes in a rat model of partial ureteral obstruction. We examined the effects of atorvastatin on histological alterations, fibrosis and function in this model.


METHODS
All rats underwent right nephrectomy. To create partial ureteral obstruction the left ureter was incorporated into the psoas muscle, which was split and reapproximated. Excretory urogram, histology, Western blot of alpha-smooth muscle actin and renal clearance were examined in rats with sham, 14-day or 30-day partial ureteral obstruction. Obstructed rats received a regular or a diet supplemented with 50 mg/kg body weight atorvastatin per day.


RESULTS
At 14 days of partial ureteral obstruction pyelogram showed hydronephrosis, which was more pronounced on obstruction day 30. Histological studies on obstruction days 14 and 30 revealed tubulointerstitial fibrosis in the medulla and cortex. Atorvastatin significantly decreased tubulointerstitial fibrosis seen in alpha-smooth muscle actin expression. On obstruction day 14 or 30 the glomerular filtration rate in rats on a regular diet was significantly lower than in sham PUO rats or rats on atorvastatin.


CONCLUSIONS
This model of partial ureteral obstruction enables chronic studies of morphological and histological changes of the obstructed kidney. It showed progressive fibrosis and decreased filtration function. Atorvastatin ameliorated fibrosis and helped preserve kidney filtration function.
Fitzgerald
John P
JP
Department of Urology, Brookdale University Hospital and Medical Center, Brooklyn, New York 11212, USA. jfitzgerald14@gmail.com
Chou
Shyan-Yih
SY
Franco
Israel
I
Mooppan
Unni M
UM
Kim
Hong
H
Saini
Rajiv
R
Gulmi
Frederick A
FA
D000818:Animals; D000069059:Atorvastatin; D002908:Chronic Disease; D005355:Fibrosis; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology*; D007684:Kidney Tubules / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014517:Ureteral Obstruction / Q000503:physiopathology* / Q000517:prevention & control*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin