Chronic inflammation, apoptosis, and impaired urothelial cell barrier function may underlie the pathophysiology of recurrent UTIs in women. Chronic inflammation may persist in the bladder wall after resolution of a UTI, which may contribute to urothelial dysfunction and barrier dysfunction, so UTI will recur easily. Impaired urothelial barrier function is largely associated with chronic inflammation and may be the cause of increased urothelial apoptosis [1].
This study was designed to investigate whether increased urothelial cell loss and recurrent urinary tract infections
(UTIs) in women.

We prospectively enrolled 33 female patients with recurrent uncomplicated UTIs, with a frequency of at least three
UTIs/year or two UTIs in the last six months, and 15 female patients as controls. Based on urine analysis and urine culture analysis, the diagnosis of bacterial cystitis was confirmed. The last episode of cystitis was observed 2-3 months before inclusion in this study. After treatment, which included antibiotic therapy, all women reported clinical recovery for at least two weeks and had a urinalysis with a white blood cell count < 5 per field and negative urine culture. All patients were admitted to the hospital for the purpose of performing video cystoscopy with a biopsy of the bladder wall. The bladder biopsy specimens were collected after one to three months after the last UTI episode had been completely resolved. All women were treated according to current guidelines.
Biopsies were obtained using cold-cup forceps. Bladder mucosa specimens biopsies were evaluated for histopathology features without knowledge of the clinical data.

At the same time, in the group of patients with infection, 31 patients (94%) showed loss of urothelium up to complete loss of urothelium (denudation); in the control group there was no loss of urothelium (p<0.0001). 
Hystopathological analysis of bladder wall biopsies obtained with endoscopic biopsy confirmed the presence of chronic inflammation in all 33 patients (100%) with recurrent UTI , as evidenced by the identified lymphocytic infiltration. A long-term inflammatory process in the wall of the bladder is accompanied by sclerosis - in our study in 70% of cases (in 23 women). The results of histopathological  study showed a violation of the integrity of the urothelium in 91% of cases (in 30 patients, respectively), and in 63.6% there was a flattening of the urothelium up to one layer, the absence of layers and/or communication between epitheliocytes up to complete denudation.

Histopathology analysis showed significantly loss of urothelium in the recurrent UTI bladder tissue compared with
the controls. Our data indicate that in chronic recurrent bacterial infections of the lower urinary tract, a chronic inflammatory process is associated with a violation of the integrity of the transitional cell epithelium of the bladder wall.
There is evidence to suggest that the abnormal function of the urothelial barrier is largely associated with chronic inflammation and may be a causative factor for increased urothelial apoptosis [2], leading to urothelial deficiency and disruption of its integrity. 
Deficiency in urothelial cell proliferation and loss of urothelium underlies the recurrent uncomplicated UTIs. For
successful treatment of recurrent UTIs, treatment aimed at restoring the urothelium is necessary.

Insufficiency of urothelial function can be caused by recurent UTI, and conversely, deficiency of the urothelium of the bladder wall can be a risk factor for chronic UTI.
These data provide new insights into the clinical management and future research of recurrent UTIs. In our opinion, for successful treatment and prevention of recurrence of UTIs, treatment aimed at accelerating the regeneration of the epithelium and restoring its integrity is mandatory.

Chuang FC, Kuo HC. Increased urothelial cell apoptosis and chronic inflammation are associated with recurrent urinary tract infection in women. PLoS One. 2013 May 15;8(5):e63760. doi: 10.1371/journal.pone.0063760.
Shie JH, Kuo HC (2011) Higher levels of cell apoptosis and abnormal E-cadherin expression in the urothelium are associated with inflammation in patients with interstitial cystitis/painful bladder syndrome. BJU Int 108: E136–141.