Urine Markers Do Not Predict Biopsy Findings or Presence of Bladder Ulcers in Interstitial Cystitis/painful Bladder Syndrome

Purpose: We tested for associations between urine markers, bladder biopsy features and bladder ulcers in interstitial cystitis/painful bladder syndrome.

Materials And Methods: Subjects were 72 patients with interstitial cystitis/painful bladder syndrome undergoing bladder distention and biopsy. Urine was collected before the procedure. Urine marker levels were correlated with biopsy and cystoscopic findings. Patients with no previous interstitial cystitis/painful bladder syndrome treatments (47) were analyzed separately from previously treated patients (25).

Results: For untreated patients urine interleukin-6 and cyclic guanosine monophosphate were associated with urothelial epidermal growth factor receptor staining (for interleukin-6 r = 0.29; 95% CI 0.07, 0.51; p = 0.01 and for cyclic guanosine monophosphate r = 0.34; 95% CI 0.13, 0.55; p = 0.002). Urine interleukin-8 was negatively associated with urothelial heparin-binding epidermal growth factor-like growth factor staining (r = -0.34; 95% CI -0.55, -0.12; p = 0.002) and positively associated with lamina propria mast cell count (r = 0.29; 95% CI 0.06, 0.52; p = 0.01). The latter association also was seen in treated patients (r = 0.46; 95% CI 0.20, 0.73; p <0.001). None of the urine markers was significantly different for ulcer vs nonulcer groups. All of the patients with ulcer had extensive inflammation on bladder biopsy including severe mononuclear cell infiltration, moderate or strong interleukin-6 staining in the urothelium and lamina propria, and leukocyte common antigen staining in more than 10% of the lamina propria. However, these features also were seen in 24% to 76% of the patients without ulcer.

Conclusions: Overall urine markers did not associate robustly with biopsy findings. The strongest association was a positive association between urine interleukin-8 levels and bladder mast cell count. Patients with ulcer consistently had bladder inflammation but the cystoscopic finding of ulcers was not a sensitive indicator of inflammation on bladder biopsy.