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

Int J Mol Sci. 2022 Oct 10;23(19):12044. doi: 10.3390/ijms231912044.

Abstract

This study investigated the usefulness of urinary biomarkers for assessing bladder condition and histopathology in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). We retrospectively enrolled 315 patients (267 women and 48 men) diagnosed with IC/BPS and 30 controls. Data on clinical and urodynamic characteristics (visual analog scale (VAS) score and bladder capacity) and cystoscopic hydrodistention findings (Hunner's lesion, glomerulation grade, and maximal bladder capacity (MBC)) were recorded. Urine samples were utilized to assay inflammatory, neurogenic, and oxidative stress biomarkers, including interleukin (IL)-8, C-X-C motif chemokine ligand 10 (CXCL10), monocyte chemoattractant protein-1 (MCP-1), brain-derived neurotrophic factor (BDNF), eotaxin, IL-6, macrophage inflammatory protein 1 beta (MIP-1β), regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and 8-isoproatane, and total antioxidant capacity. Further, specific histopathological findings were identified via bladder biopsy. The associations between urinary biomarker levels and bladder conditions and histopathological findings were evaluated. The results reveal that patients with IC/BPS had significantly higher urinary MCP-1, eotaxin, TNF-α, PGE2, 8-OHdG, and 8-isoprostane levels than controls. Patients with Hunner's IC (HIC) had significantly higher IL-8, CXCL10, BDNF, eotaxin, IL-6, MIP-1β, and RANTES levels than those with non-Hunner's IC (NHIC). Patients with NHIC who had an MBC of ≤760 mL had significantly high urinary CXCL10, MCP-1, eotaxin, IL-6, MIP-1β, RANTES, PGE2, and 8-isoprostane levels and total antioxidant capacity. Patients with NHIC who had a higher glomerulation grade had significantly high urinary MCP-1, IL-6, RANTES, 8-OHdG, and 8-isoprostane levels. A significant association was observed between urinary biomarkers and glomerulation grade, MBC, VAS score, and bladder sensation. However, bladder-specific histopathological findings were not well correlated with urinary biomarker levels. The urinary biomarker levels can be useful for identifying HIC and different NHIC subtypes. Higher urinary inflammatory and oxidative stress biomarker levels are associated with IC/BPS. Most urinary biomarkers are not correlated with specific bladder histopathological findings; nevertheless, they are more important in the assessment of bladder condition than bladder histopathology.

Keywords: biomarker; bladder pain syndrome; cytokine; interstitial cystitis.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Antioxidants / metabolism
  • Biomarkers / metabolism
  • Brain-Derived Neurotrophic Factor / metabolism
  • Chemokine CCL2 / metabolism
  • Chemokine CCL4 / metabolism
  • Chemokine CCL5 / metabolism
  • Cystitis, Interstitial* / diagnosis
  • Cystitis, Interstitial* / urine
  • Dinoprostone / metabolism
  • Female
  • Humans
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Ligands
  • Male
  • Retrospective Studies
  • Tumor Necrosis Factor-alpha / metabolism
  • Urinary Bladder / pathology

Substances

  • Antioxidants
  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • Chemokine CCL2
  • Chemokine CCL4
  • Chemokine CCL5
  • Interleukin-6
  • Interleukin-8
  • Ligands
  • Tumor Necrosis Factor-alpha
  • 8-Hydroxy-2'-Deoxyguanosine
  • Dinoprostone