Presentation Authors: Ramakrishna Venkatesh*, Nick Staten, Michael Talcott, Suellen Greco, Colleen Haug, Neel Raval, Carlos Puyo, Saint Louis, MO
Introduction: The basic mechanisms of ureteral stent morbidity is not well understood. Reducing the inflammatory process associated with a stent may decrease symptoms related to ureteral stents. We evaluated the acute and sub-acute effects of a ureteral stent coated with HCQ+NAC (hydroxychroloquine+N-acetylcysteine)on the porcine ureteral wall.
Methods: We evaluated the inflammatory effects of a 4.7Frx22 cm ureteral stent coated with HCQ-NAC at 6 hours & 7 days post-stent placement, and compared with an uncoated stent (PercuflexTM,Microvasive). 14 domestic female pigs (45-50lbs) 3 pigs/group for 6hr study and 4 pigs/group for 7-day study, had stents placed by cystoscopic guidance over a guidewire under fluoroscopy. Urine & blood samples was collected pre and post stent placement and segments of ureters (proximal and distal) & bladder wall were harvested for H&E staining after euthanizing the animals. Cells from urine & blood samples were isolated, stained for NF-kB(pro-inflammatory activation) including markers for reactive oxygen species (ROS) and analyzed via flow cytometry. Inflammation of the ureter and bladder wall was reported through a scoring system (0-4).
Results: As expected the control ureter with no stent showed very minimal reaction with occasional infiltration of mononuclear cells in the mucosa at 6 hours & 7 days. Interestingly at 6 hours in the coated stent group, there was extensive epithelial loss & subepithelial necrosis (6-11 score). In comparison, the uncoated stent groups showed early collagen deposition and less inflammation(score of 4-8). At 7 days, the uncoated stent group showed epithelial mucinous metaplasia and the coated stent group showed in addition to collagen deposition. Flow cytometry data showed no statistically significant difference in ROS production and NFkB staining of cells between coated & uncoated stent groups.
Conclusions: Though there was significant inflammation of ureteral wall in the HCQ-NAC coated ureteral stent group at 6 hours, there was reduced inflammation at 7 days. This could be related to drug dosage and delivery factors. Ureteral wall staining following stenting for markers of pro-inflammatory activation pathways including NF-kB and reactive oxygen species may provide better understanding of stent induced inflammation.