BLADDER WALL REMODELING IN RECURRENT URINARY TRACT INFECTIONS

Abstract

Recurrent urinary tract infections (rUTIs) present a persistent clinical challenge due to their high prevalence, especially among women, and their propensity to induce chronic structural and functional changes in the bladder wall. This study aimed to investigate the extent of bladder wall remodeling in individuals with rUTIs using a multimodal approach encompassing clinical, histopathological, immunohistochemical, and molecular analyses. A cohort of patients with a documented history of rUTIs was compared to age- and sex-matched controls. Histopathological assessments revealed a significant increase in fibrosis scores (mean 2.6 ± 0.4) and marked urothelial disruption in rUTI patients, in contrast to minimal alterations in control tissues. Immunohistochemical staining demonstrated elevated expression of immune cell markers CD3 and CD68, along with increased deposition of extracellular matrix proteins such as collagen I and fibronectin. Conversely, epithelial markers E-cadherin and ZO-1 showed notable downregulation, suggesting compromised barrier function. Gene expression analysis via qPCR confirmed a several-fold upregulation of key pro-inflammatory and fibrotic genes—IL-6, TNF-α, TGF-β1, and COL1A1—in the rUTI group. Clinically, these molecular and structural alterations corresponded with higher infection recurrence rates and increased history of catheterization. The integrated findings provide robust evidence that rUTIs contribute to a self-sustaining cycle of bladder wall remodeling, characterized by chronic inflammation and fibrosis, which likely exacerbate symptom burden and predispose patients to future infections. These insights highlight the urgent need for therapies targeting the inflammatory and fibrotic pathways alongside antimicrobial treatment to break the recurrence cycle and preserve bladder function. This study emphasizes the importance of comprehensive bladder assessment in patients with recurrent infections and supports a multidisciplinary strategy for long-term disease management.