From Infection to Fibrosis: The Role of Uropathogens in Chronic Kidney Disease Progression

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide and are traditionally considered acute and self-limited conditions. However, emerging evidence suggests that recurrent and persistent UTIs may contribute to chronic kidney disease (CKD) progression through complex interactions between uropathogens and host responses. This review examines the pathophysiological mechanisms linking UTIs caused by uropathogenic Escherichia coli, Klebsiella spp., and Enterococcus spp. to CKD development. Distinct pathogen-specific strategies, including intracellular persistence, biofilm formation, and chronic colonization, enable sustained infection and recurrent inflammatory insults. These processes activate key molecular pathways, including innate immune signalling, inflammasome activation, oxidative stress, and fibrotic remodelling. The convergence of these mechanisms leads to tubular injury, nephron loss, and a progressive decline in renal function. A comprehensive mechanistic model integrating pathogen-specific persistence strategies and host-mediated responses, including inflammation, inflammasome activation, oxidative stress, and fibrosis, is illustrated in Figure X, highlighting how recurrent and persistent UTIs may drive CKD progression. In addition, biomarkers reflecting inflammation (IL-6, CRP), tubular injury (NGAL, KIM-1), and fibrosis (TGF-β, fibronectin) provide a translational bridge between molecular mechanisms and clinical practice. Host factors such as diabetes, immune dysfunction, and microbiome alterations further modulate disease trajectory, while antibiotic resistance contributes to persistent infection and increased renal risk. These findings underscore the importance of early detection, pathogen-specific management, and biomarker-guided monitoring. Collectively, this review supports a paradigm shift recognizing UTIs not merely as acute infections but also as potential contributors to CKD progression, with important implications for prevention and therapeutic strategies.