Presentation Authors: Amy Kuprasertkul*, Luming Chen, Kim Orth, Dallas, TX, Nicole J. DeNisco, Richardson, TX, Philippe Zimmern, Dallas, TX
Introduction: Recurrent urinary tract infection (RUTI) in has become an important clinical problem with limited therapeutic options. Cystoscopy with fulguration of trigonitis (CFT) is a treatment option for women for whom antibiotic therapy is no longer effective or well-tolerated. CFT effectively resolves trigonitis and prevents RUTI in approximately 70% of cases, but the scientific basis for this is poorly understood (1). One hypothesis is that the fulgurated areas no longer express the surface proteins, such as uroplakin-3, that pathogens use to attach to and invade the urothelium (2). In this study, we evaluated the expression of uroplakin-3a along the luminal surface of umbrella cells in biopsies from both naive and previously fulgurated bladder regions.
Methods: Following IRB approval, cold cup bladder biopsies of both regions of visible cystitis (infected) and no visible cystitis (control) were obtained from postmenopausal women with antibiotic refractory, uncomplicated RUTI undergoing CFT under anesthesia. In patients with prior CF, the &[Prime]control&[Prime] region was the previously fulgurated region as cystitis was never visible in these areas. Control and infected biopsies from 5 patients, 2 with a prior CFT and 3 naive, were analyzed by immunofluorescence confocal microscopy using antibodies against uroplakin-3a (Novus, rabbit). 10 representative images were taken of the urothelial region of each section and scored using the criteria described in the table legend
Results: The uroplakin-3a scoring results are presented in the table along with relevant clinical data. In healthy tissue, uroplakin-3 staining is observed as a contiguous line on the luminal surface of umbrella cells. Contiguous urothelial staining of uroplakin-3a was only observed in the control regions of naive patients (N=3). No uroplakin-3a staining was detected in the control regions ofpatients with a prior CFT (N=2). The infected regions showed varying degrees of uroplakin-3a staining, but always â‰¤ the matched control region.
Conclusions: In this preliminary study, no uroplakin-3a expression was observed in the urothelium of biopsies from visually uninfected regions of the bladder that had been previously fulgurated. These results suggest that the presumptive umbrella cells of the healed urothelium post-CFT no longer express uroplakin-3a.