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BASIC
AND TRANSLATIONAL UROLOGY
doi: 10.1590/S1677-553820100002000023
Atorvastatin
protects renal function in the rat with acute unilateral ureteral obstruction
Kamdar C, Chou SY, Mooppan UM, Kim H, Gulmi FA
Department of Urology, Brookdale University Hospital and Medical Center,
Brooklyn, New York, USA
Urology. 2010; 75: 853-7
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Objectives:
To examine the effects of atorvastatin on renal hemodynamics and urinary
microalbumin levels in rats with acute unilateral ureteral obstruction
(UUO). Previous studies have demonstrated that treatment with statins
attenuated renal structural damages in rodents with chronic UUO. However,
it is not known whether statins afford protection of renal function.
Methods: UUO was created by ligation of the left ureter in rats maintained
on a regular diet or the same diet but supplemented with atorvastatin
(50 mg/kg/d) for 2 weeks. Renal clearance experiments were performed
after release of UUO at 1 hour, 6 hours, or 12 hours.
Results: Atorvastatin treatment lowered plasma triglyceride but not
cholesterol levels. Both glomerular filtration rate and effective
renal plasma flow were significantly greater in atorvastatintreated
rats after release of UUO at 1 hour, 6 hours, and 12 hours. Significant
reduction of urinary microalbumin to creatinine ratios occurred in
the atorvastatin-treated group at 12 hours but not earlier.
Conclusions: Atorvastatin treatment affords protection of renal function
in acute UUO and reduces urinary microalbumin levels without lowering
cholesterol levels. This pleiotropic action of atorvastatin on preservation
of renal hemodynamics may be important in attenuating subsequent renal
structural injury in chronic UUO.
- Editorial
Comment
Previous studies examined molecular markers of fibrosis and histologic
changes in chronically obstructed kidney. This is the first research
that analyzed the effects of statins (atorvastatin) on renal hemodynamics
of kidneys with ureter acutely obstructed unilaterally. The present
investigation showed by the first time that treatment with atorvastatin
in rats with acute unilateral ureteral obstruction resulted in improvement
in renal perfusion and filtration function.
The authors emphasized that these findings raise the possibility that
some of the benefits of statins in the clinical trials may originate
from the pleiotropic effects of statins and not specifically from
the lipid-lowering effect alone. Also, it is worth to note that the
dose of statin used in the present study is proportionally much higher
than the doses current used in clinical practice. The authors also
remembered that other studies also used supra-pharmacological doses
of statins to demonstrate attenuation of tubulo-interstitial inflammation
and fibrosis in rats with unilateral ureteral obstruction. Therefore,
the dosage of statins required to exert their pleiotropic actions
is still unknown and remains to be determined. Anyway, the present
study shown that treatment with a statin in rats with acute unilateral
ureteral obstruction, resulted in improvement in renal perfusion and
filtration function. This open new avenue for renal protective agents.
Dr.
Francisco J. B. Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, RJ, Brazil
E-mail: sampaio@urogenitalresearch.org
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