Use of Urinary Cytokine and Chemokine Levels for Identifying Bladder Conditions and Predicting Treatment Outcomes in Patients with Interstitial Cystitis/Bladder Pain Syndrome

Abstract

Background: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a condition causing bladder inflammation. Urinary biomarkers have been assessed as suitable for the diagnosis and treatment. This study aimed at investigating the role of urinary biomarkers in identifying bladder conditions and predicting the treatment outcome of IC/BPS. Methods: A total of 309 patients with IC/BPS and 30 controls were enrolled in this study. All patients underwent a comprehensive urological workup of symptoms, pain severity, and cystoscopic hydrodistention findings including maximal bladder capacity (MBC) and glomerulation grade. Urine samples were collected to investigate the levels of urinary cytokines and chemokines. According to MBC and glomerulation grade, patients with IC/BPS were further classified into the Hunner’s IC (HIC) and non-HIC groups. The urinary biomarkers between IC/BPS and control groups and HIC and non-HIC groups were compared. Moreover, the treatment response was graded according to global response assessment (GRA) scores, and urinary biomarker levels were analyzed based on different GRAs. Results: Patients with IC/BPS had significantly high urinary monocyte chemoattractant protein-1, eotaxin, tumor necrosis factor -alpha (TNF-α), and prostaglandin E2 levels. Significantly higher levels of urinary interleukin-8, C-X-C motif chemokine ligand 10 (CXCL 10), brain-derived neurotrophic factor, eotaxin, and regulated-on-activation, normal T-cell expressed and secreted (RANTES) were noted in HIC than those with non-HIC and controls. Among all biomarkers, TNF-α had the best sensitivity, specificity, positive predictive value, and negative predictive value. There was a significant correlation between biomarker levels and GRA. Conclusions: Significantly higher urine cytokines and chemokine levels were found in patients with IC/BPS. Most urinary biomarkers were significantly associated with MBC, glomerulation grade, and treatment outcome.

Usefulness of Urinary Biomarkers for Assessing Bladder Condition and Histopathology in Patients with Interstitial Cystitis/Bladder Pain Syndrome

“…In our previous paper, we did not measure urine levels of oxidative stress biomarkers. We also did not compare these urine biomarkers with bladder conditions and histopathological findings [ 12 ]. The results of this study help us understand the pathophysiology of IC/BPS.…”

“…Therefore, a low bladder capacity might be associated with a distinct bladder-centric IC/BPS phenotype [ 11 ]. According to these clinical and proteomic results, IC/BPS might be caused by not only conditions confined to the bladder but also mental factors such as internal conflict and stress disorders [ 12 ]. Bladder symptoms might be, in part, attributed to the effects of systemic medical comorbidities.…”

“…Thus, 10 targeted analytes, namely, IL-8, CXCL10, MCP-1, eotaxin, IL-6, macrophage inflammatory protein 1 beta (MIP-1β), RANTES, TNF-α (catalog number HCYTA-60K), BDNF (catalog number HNDG3MAG-36K), and PGE2 (Cayman Chemical Co., Ann Arbor, MI, USA, No. 514010), were selected [ 8 , 11 , 12 , 20 ]. Then, these analytes were measured using the multiplex kit (catalog number: HCYTMAG-60K-PX30).…”

“…Patients with IC/BPS have significantly higher levels of urinary cytokines and chemokines such as monocyte chemoattractant protein 1 (MCP-1), eotaxin, tumor necrosis factor-alpha (TNF-α), and prostaglandin E2 (PGE2) [ 11 ]. Most urinary biomarkers were significantly associated with maximal bladder capacity (MBC), glomerulation grade, and treatment outcome evaluated using the global response assessment [ 12 ]. Patients with HIC had significantly higher levels of urinary interleukin-8 (IL-8), C-X-C motif chemokine ligand 10 (CXCL10), brain-derived neurotrophic factor (BDNF), and eotaxin, and regulated, on activation, normal T cell expression and secretion (RANTES) than those with NHIC and controls.…”

“…Patients with HIC had significantly higher levels of urinary interleukin-8 (IL-8), C-X-C motif chemokine ligand 10 (CXCL10), brain-derived neurotrophic factor (BDNF), and eotaxin, and regulated, on activation, normal T cell expression and secretion (RANTES) than those with NHIC and controls. Among all urinary biomarkers, TNF-α has the best sensitivity, specificity, and positive and negative predictive values [ 12 ]. In addition to inflammatory cytokines, urinary oxidative stress biomarkers can be novel biomarkers in patients with IC/BPS.…”