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

Jiang, Yuan‐Hong; Jhang, Jia‐Fong; Hsu, Yuan-Hsiang; Kuo, Hann‐Chorng

doi:10.3390/ijms231912044

Cited by 24 publications

(19 citation statements)

References 26 publications

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“…We also demonstrated increased expression of inflammatory mediators in the urinary bladder including neurotrophic factors (e.g., NGF, BDNF), chemokines (CXC) and IL-6 expression in the urinary bladder consistent with a large body of literature demonstrating roles for inflammatory mediators in preclinical animal models of and in IC/BPS patients (18,(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). Urinary bladder neurotrophic factor (i.e., NGF, BDNF), CXCL9, CXCL10 and IL-6 expression was increased in mice with CYP alone, RVS alone and CYP+RVS compared to control mice.…”

Section: Discussionsupporting

confidence: 83%

“…In this paper, we describe our characterization of the SISE model including, bladder function with conscious, open outlet continuous cystometry and somatic sensitivity with von Frey filament testing. We have also examined corticosterone expression, and expression of inflammatory mediators including neurotrophic factor (NGF, BDNF) (18)(19)(20), chemokine (CXC) and interleukin-6 (IL-6) (18,(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34) expression in the urinary bladder. These initial results demonstrated that CYP alone, or RVS alone creates a change in the inflammatory environment of the urinary bladder and a systemic increase in corticosterone expression but does not result in a change in bladder function or somatic sensitivity until CYP is combined with RVS (CYP+RVS).…”

Section: Introductionmentioning

confidence: 99%

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Stress-induced symptom exacerbation: Stress increases voiding frequency, somatic sensitivity, and urinary bladder inflammation when combined with low concentration cyclophosphamide treatment in mice

Girard¹,

Campbell²,

Vizzard³

2023

Front. Urol.

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Symptom exacerbation due to stress is prevalent in many disease states, including functional disorders of the urinary bladder (e.g., overactive bladder (OAB), interstitial cystitis/bladder pain syndrome (IC/BPS)); however, the mechanisms underlying the effects of stress on micturition reflex function are unclear. In this study we designed and evaluated a stress-induced symptom exacerbation (SISE) mouse model that demonstrates increased urinary frequency and somatic (pelvic and hindpaw) sensitivity. Cyclophosphamide (CYP) (35 mg/kg; i.p., every 48 hours for a total of 4 doses) or 7 days of repeated variate stress (RVS) did not alter urinary bladder function or somatic sensitivity; however, both CYP alone and RVS alone significantly (p ≤ 0.01) decreased weight gain and increased serum corticosterone. CYP treatment when combined with RVS for 7 days (CYP+RVS) significantly (p ≤ 0.01) increased serum corticosterone, urinary frequency and somatic sensitivity and decreased weight gain. CYP+RVS exposure in mice significantly (p ≤ 0.01) increased (2.6-fold) voiding frequency as we determined using conscious, open-outlet cystometry. CYP+RVS significantly (p ≤ 0.05) increased baseline, threshold, and peak micturition pressures. We also evaluated the expression of NGF, BDNF, CXC chemokines and IL-6 in urinary bladder in CYP alone, RVS alone and CYP+RVS mouse cohorts. Although all treatments or exposures increased urinary bladder NGF, BDNF, CXC and IL-6 content, CYP+RVS produced the largest increase in all inflammatory mediators examined. These results demonstrated that CYP alone or RVS alone creates a change in the inflammatory environment of the urinary bladder but does not result in a change in bladder function or somatic sensitivity until CYP is combined with RVS (CYP+RVS). The SISE model of CYP+RVS will be useful to develop testable hypotheses addressing underlying mechanisms where psychological stress exacerbates symptoms in functional bladder disorders leading to identification of targets and potential treatments.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Stress-induced symptom exacerbation: Stress increases voiding frequency, somatic sensitivity, and urinary bladder inflammation when combined with low concentration cyclophosphamide treatment in mice

Girard¹,

Campbell²,

Vizzard³

2023

Front. Urol.

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“…The urinary oxidative stress biomarkers 8-OHdG and 8-isoprostane also showed a high diagnostic ability to distinguish the European Society for the Study of Interstitial Cystitis (ESSIC) type 2 IC/BPS patients from controls [ 20 ]. These urinary biomarker levels are likely to reflect the bladder inflammatory condition rather than the underlying histopathological status in patients with IC/BPS [ 28 ]. Urinary cytokine profiles are different between patients with ESSIC type 2 IC/BPS and OAB [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Discriminating Different Bladder and Bladder Outlet Dysfunctions by Urinary Biomarkers in Women with Frequency–Urgency Syndrome

Jhang

Jiang

2023

Biomedicines

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Objectives: To investigate the role of urinary biomarkers in discriminating different bladder and bladder outlet dysfunctions in women with frequency–urgency syndrome. Materials and Methods: Urine samples collected from 146 women with frequency–urgency syndrome and 34 controls were investigated. All patients were included in previous clinical trials of functional urology studies and underwent a videourodynamic study. Patients with frequency–urgency syndrome were subdivided into idiopathic detrusor overactivity (IDO), neurogenic detrusor overactivity (NDO), dysfunctional voiding (DV), and hypersensitive bladder (HSB) subgroups. Urine samples were collected before any treatment, and urinary inflammatory proteins (interleukin- (IL-) 1β, IL-2, IL-6, IL-8, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF)), neurogenic proteins (nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and prostaglandin E2 (PGE2)), and oxidative stress biomarkers (8-isoprostane, total antioxidant capacity (TAC), and 8-hydroxydeoxyguanosine (8-OHdG)) were measured and compared between the different OAB subgroups and controls. Results: Of the 146 patients, 31 had IDO, 41 had NDO, 45 had DV, and 29 had HSB. The control group included 34 women. The patients with HSB had lower urinary TAC and IL-2 levels than the controls. The patients with IDO, NDO, and DV had significantly higher urinary TNF-α levels than those with HSB. The patients with IDO and NDO showed an increase in the urinary 8-isoprostane levels, whereas the patients with IDO had higher urinary IL-2, NGF, and BDNF levels than those with NDO. The other urinary inflammatory biomarkers did not show enough significant differences to discriminate between the different bladder and bladder outlet dysfunctions. Conclusions: The urinary levels of inflammatory, neurogenic, and oxidative stress biomarkers varied widely among the patients with bladder and bladder outlet dysfunction. This study’s results provide evidence that women with frequency–urgency syndrome and different urodynamic subtypes have varying bladder inflammation and oxidative stress conditions, which might have an impact on treatment outcomes.

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“…6 Urinary biomarkers are the most explored and may be used as tools to distinguish IC/BPS from other bladder diseases. 7,8 To our knowledge, no study has been conducted on blood biomarkers in humans. Therefore, we initiated clinical studies on blood biomarkers.…”

Section: Introductionmentioning

confidence: 99%

“…Although stool and bladder tissue have been investigated as potential sources of biomarkers, no universal biomarkers have been identified for clinical diagnosis 6 . Urinary biomarkers are the most explored and may be used as tools to distinguish IC/BPS from other bladder diseases 7,8 . To our knowledge, no study has been conducted on blood biomarkers in humans.…”

Section: Introductionmentioning

confidence: 99%

Serum anandamide and lipids associated with linoleic acid can distinguish interstitial cystitis/bladder pain syndrome from overactive bladder: An exploratory study

Torimoto,

Ueda,

Gotoh

et al. 2023

LUTS

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ObjectivesDiagnosing interstitial cystitis/bladder pain syndrome presents a major challenge because it relies on subjective symptoms and empirical cystoscopic findings. A practical biomarker should discriminate diseases that cause increased urinary frequency, particularly overactive bladder. Therefore, we aimed to identify blood biomarkers that can discriminate between interstitial cystitis/bladder pain syndrome and overactive bladder.MethodsWe enrolled patients with Hunner‐type interstitial cystitis (n = 20), bladder pain syndrome (n = 20), and overactive bladder (n = 20) and without lower urinary tract symptoms (controls, n = 15) at Ueda Clinic and Nara Medical University Hospital from February 2020 to August 2021. The degree of interstitial cystitis/bladder pain syndrome symptoms was evaluated using the interstitial cystitis symptom and problem indices. Metabolomics analysis was performed on 323 serum metabolites using liquid chromatography time‐of‐flight mass spectrometry.ResultsIn the Hunner‐type interstitial cystitis or bladder pain syndrome group, we observed smaller relative areas, including anandamide, acylcarnitine (18:2), linoleoyl ethanolamide, and arachidonic acid, compared to those in the overactive bladder or control group. Notably, the differences in the relative areas of anandamide were statistically significant (median: 3.950e‐005 and 4.150e‐005 vs. 8.300e‐005 and 9.800e‐005), with an area under the curve of 0.9321, demonstrating its ability to discriminate interstitial cystitis/bladder pain syndrome.ConclusionsSerum anandamide may be a feasible diagnostic biomarker for interstitial cystitis/bladder pain syndrome. Reduced serum anandamide levels may be associated with pain and inflammation initiation, reflecting the pathology of interstitial cystitis/bladder pain syndrome. Furthermore, our findings suggest that abnormal linoleic acid metabolism may be involved in the pathogenesis of interstitial cystitis/bladder pain syndrome.

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

Cited by 24 publications

References 26 publications

Stress-induced symptom exacerbation: Stress increases voiding frequency, somatic sensitivity, and urinary bladder inflammation when combined with low concentration cyclophosphamide treatment in mice

Stress-induced symptom exacerbation: Stress increases voiding frequency, somatic sensitivity, and urinary bladder inflammation when combined with low concentration cyclophosphamide treatment in mice

Discriminating Different Bladder and Bladder Outlet Dysfunctions by Urinary Biomarkers in Women with Frequency–Urgency Syndrome

Serum anandamide and lipids associated with linoleic acid can distinguish interstitial cystitis/bladder pain syndrome from overactive bladder: An exploratory study

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