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Potential urine and serum biomarkers for patients with overactive bladder and interstitial cystitis/bladder pain syndrome

Hann-Chorng Kuoa, Hsin-Tzu Liua, b, Jia-Heng Shiea

a Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan
b Ph.D. Program in Pharmacology and Toxicology, School of Medicine, Tzu Chi University, Hualien, Taiwan

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Abstract
There is a lack of consensus on the pathophysiology of overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS). The chronic pain symptoms in IC/BPS and OAB refractory to antimuscarinic agents may be due to central nervous system sensitization and persisting abnormalities in the bladder wall that activate the afferent sensory system. Evidence also indicates that IC/BPS is a heterogeneous syndrome and that the two subtypes, the ulcer type (classic) and nonulcer disease, represent different disease entities. There is a need for noninvasive markers for the differential diagnosis of the subtypes of IC/BPS and OAB. Increased levels of nerve growth factor (NGF) have been reported in the bladder tissue and urine of patients with OAB and IC/PBS. Recent studies have also revealed that serum NGF and C-reactive protein (CRP) are elevated in these two diseases. IC/BPS, but not OAB, involves an aberrant differentiation program in the bladder urothelium that leads to altered synthesis of several proteoglycans, cell adhesion and tight junction proteins, and bacterial defense molecules. These findings have led to the rationale for identifying urinary biomarkers to detect IC/BPS in patients with frequency urgency syndrome such as OAB-dry and OAB-wet. Recently, the markers that have been the focus of the most research are antiproliferative factor, epidermal growth factor, heparin-binding epidermal growth factor, glycosaminoglycans, and bladder nitric oxide. In addition to these urothelial defense molecules, inflammatory proteins in the urine and serum have been found to possess important roles in the pathogenesis of IC/BPS and OAB. The urinary proteome is a potential easily accessible source of biomarkers for differentiation between inflammatory bladder disorders. Analysis of multiple urinary proteins and serum cytokines is a convenient approach to monitoring the activation of inflammatory cells in the bladder tissue. Differences in urinary proteins and serum cytokines might provide a diagnostic basis for IC/BPS and could be a tool for the differential diagnosis between IC/BPS and OAB.

Keywords
Biomarker; Chemokines; Interstitial cystitis; Overactive bladder; Proteomics


 

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