Recurrent urinary tract infection (rUTI) is often associated with relapses that are difficult to prevent. It is important to search for markers of the bladder wall inflammatory process, allowing to predict the recurrence risk, the severity of cystitis and determine inflammation when urine tests are normal. It is generally accepted that calprotectin in the urinary bladder may be produced mainly by neutrophils and is associated with pyuria. We supposed that calprotectin levels may be elevated in rUTI not only in exacerbation, but also in remission.
The aim of this study was to investigate the role of calprotectin as a diagnostic marker of inflammation in rUTI outside exacerbation.

The study prospectively included 61 patients with a verified diagnosis of uncomplicated rUTI. Аny kidney disease, neoplastic processes, complicating factors, etc., increasing the level of urine calprotectin were excluded. All patients with rUTI underwent video cystoscopy with a bladder wall biopsy using cold forceps, aimed at excluding a malignant process and confirming bladder inflammation, squamous metaplasia at the bladder trigone. The control group included 27 practically healthy women of reproductive age. Calprotectin, IL-6, leukocytes levels were measured in urine samples in both groups using enzyme-linked immunosorbent assay.

The median age of women with rUTI was significantly higher than healthy women, 35.6 and 26.3 (p = 0.04), respectively.   A direct correlation of medium strength was found between the presence of chronic recurrent cystitis and urinary calprotectin level (R = 0.649, p = 0.0000), pyuria (R = 0.519, p = 0.0000). Therefore, a comparative analysis was done to evaluate the differences in calprotectin, IL-6 levels, and the presence or absence of elevated leukocyte levels in urine. According to the received data, an increase in urine IL-6 level was associated with an increase in urine leukocytes (p=0.012), while pyuria was not associated with calprotectin level in urine.
Histopathological examination revealed an inflammatory process of the bladder wall in patients with chronic cystitis. In 67.2% of cases, the inflammation was combined with squamous metaplasia of the bladder trigone urothelium. It correlated with the elevated calprotectin level in urine (R = 0. 41, p = 0.01).

Women with rUTI have elevated levels of calprotectin and IL-6 in urine, while the level of calprotectin in urine is affected not only by pyuria, but also by other factors. We assume that the elevated level of calprotectin in urine may be due to increased expression of S100A8/S100A9 on the surface of the squamous cell epithelium of the bladder. From our data it follows that calprotectin may well cause the development of an abacterial inflammatory process in the wall of the bladder without increasing the level of leukocytes in the urine, in connection with which the diagnostic significance of calprotectin as a marker of inflammation in the wall of the bladder is especially valuable and high in cases where urine tests are normal.

Elevated levels of calprotectin in urine in the absence of pyuria may indicate a chronic inflammatory process in the bladder wall, possibly associated with squamous cell metaplasia.