Effect of Everolimus-Coated Ureteral Stent on Ureteral Anastomosis and Renal Ischemia-Reperfusion Damage: A Rabbit Experimental Model

Abstract

Objective: Ureteral stricture is defined as the narrowing of the ureter, which leads to functional impairment. This study aims to assess the fibrosis-reducing impact of everolimus, an mTOR inhibitor, on ureteral anastomoses and their potential to mitigate ischemia-reperfusion injury (IRI) in the ipsilateral kidney.

Materials-Methods: Sixteen New Zealand rabbits were randomized into four groups. Group 1: it was determined as the control group. Right-sided kidneys were used in all groups. The renal pedicle was clamped with a noncrushing clamp for 30 min to create IRI. Subsequently, the ureter was transected from the midline. End-to-end anastomosis was performed without the use of a ureteral stent. Group 2: similar procedures were performed as Group 1. Differently, everolimus (Certican, 0.75 mg tablet, Novartis) tablet at a dose of 1 mg/kg was administered orally as once daily for 3 days following the surgical procedure. Group 3: following IRI similar to the other groups, ureter end-to-end anastomosis was performed using a bare stent. Group 4: after similar procedures, end-to-end anastomosis was performed using double J stents coated with everolimus. All rabbits were followed for 21 days after the initial surgeries and sacrificed at the end of this period. Both kidneys and ureters of the subjects were resected en bloc for histopathological and biochemical analysis.

Results: There was less renal inflammatory cell infiltration, interstitial edema, vacuolar degeneration, and fibrosis in both oral everolimus and everolimus-coated stent groups than those in the other groups.

Conclusion: We conclude that everolimus has the potential to prevent ureteral strictures.