Management of radiotherapy induced rectourethral fistula

Abstract

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.