Pathogenesis of urinary tract infection: an update

Abstract

Urinary tract infection is the second most common bacterial infection in children. It may cause renal scarring leading to secondary hypertension and chronic kidney disease. Recent information has greatly improved our understanding of the pathogenesis of urinary tract infection and renal scarring. Urothelium, an anatomical barrier for innate immune responses, expresses toll-like receptors with the capacity to recognize pathogen-associated molecular patterns. Engagement of toll-like receptors can lead to uroepithelial cell activation and production of inflammatory mediators. These include complement proteins, other bactericidal peptides, cytokines, chemokines, defensins and adhesion molecules. The resulting inflammatory infiltrate serves to aid bacterial clearance but can also lead to renal damage. Furthermore, interactions between urinary proteins, such as Tamm-Horsfall protein, and TLR-4 add to the complexity of this defense system. Interindividual variability in cellular response may in part be responsible for variable clinical outcomes. Polymorphisms in a number of candidate genes in this host defense mechanism may be involved in determining those patients who are susceptible to recurrent infections and renal scarring following urinary tract infection. Further understanding of the basic molecular mechanisms of urinary tract infection and translating these bench data to the bedside holds the promise of improving diagnosis and therapeutic strategies of treating urinary tract infection and preventing recurrence and renal scarring.