Introduction and hypothesis: Bladder pain syndrome (BPS) is a disease of unknown etiology defined as an unpleasant sensation related to the bladder, associated with lower urinary tract symptoms of more than 6 weeks' duration, in the absence of any identifiable causes. Despite its impact on quality of life (QoL) and socioeconomic burden, there are no objective methods for the diagnosis or assessment of therapeutic response. We systematically reviewed biomarkers associated with BPS to update the current knowledge on this issue.
Methods: A systematic review of the Cochrane Library, Embase, PubMed/MEDLINE, LILACS, SCOPUS, and ClinicalTrials.gov databases was conducted following the PRISMA statement. Original articles investigating biomarkers for the diagnosis or symptom assessment of patients with BPS were assessed; no language restrictions were applied. Animal or post-mortem studies were excluded.
Results: Of the 478 records retrieved, 11 articles were included. MIF, NGF, Etio-S, APF, and a combined methylhistamine/Il-6 model were increased in BPS urine samples versus controls. Also increased were glyceraldehyde in stool, in addition to the expression of some genes (ARID1A, ARF, CHAT, eNOS, GLI-1, iNOS, MCP-1, NGF, WNT-8A, WNT-10A), nerve density, IL-16, VCAM-1, and ICAM-1 in bladder tissue specimens. In contrast, some fecal bacteria, expression of other genes (CHT, HB-EGF, OCT-1, SMRT-1, WNT11) in the bladder urothelium, and urinary DNA methylation in CpG-sites, MCP-3, G5P1, and HB-EGF were decreased in BPS. As none of the biomarkers was studied more than once, a Forest plot could not be constructed. Only 4 articles reported the relation of biomarkers to symptom scores.
Conclusions: Potential biomarkers for BPS in urine, stool, and bladder biopsy specimens are described. Further research is needed before their use in clinical practice.
Keywords: Diagnosis; Interstitial cystitis; Signs and symptoms.