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29-01-2025 | Biomarkers | Urology – Original Paper

Revealing distinct treatment mechanisms and outcome correlations in patients with interstitial cystitis/bladder pain syndrome after different bladder therapies through urinary biomarker analysis

Authors: Yu-Chieh Chiu, Ping-Chiao Tsai, Jia-Fong Jhang, Hann-Chorng Kuo

Published in: International Urology and Nephrology

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Abstract

Purpose

Urinary cytokine changes may serve as biomarkers to assess treatment outcomes for interstitial cystitis/bladder pain syndrome (IC/BPS). This study analyzed the changes in urinary cytokines following various bladder therapies and explored their clinical significance in therapeutic mechanisms.

Methods

A total of 122 patients with IC/BPS treated with platelet-rich plasma (PRP), botulinum toxin-A (BoTN-A), hyaluronic acid (HA), or low-energy shock wave (LESW) were evaluated. Urinary inflammatory and oxidative stress biomarkers were measured at baseline and at 3 months posttreatment. Treatment outcomes were assessed using the Global Response Assessment (GRA), a 10-point visual analog score for pain, and the O’Leary–Saint Symptom Score (OSS). A GRA ≥ 2 was considered indicative of effective treatment.

Results

Significant symptom improvement was observed in patients treated with PRP and BoNT-A but not with LESW or HA. At 3 months post-treatment, PRP therapy led to decreased urinary 8-isoprostane and total antioxidant capacity levels, while BoNT-A therapy reduced monocyte chemotactic protein-1 and 8-hydroxy-2′-deoxyguanosine levels. HA therapy did not alter urinary biomarker levels, whereas LESW therapy increased macrophage inflammatory protein-1 beta and tumor necrosis factor-α levels. Patients with significant urinary biomarker reductions (GRA ≥ 2) demonstrated clinical improvement at 3 months.

Conclusion

PRP or BoNT-A exhibits anti-inflammatory effects, reflected by reductions in urinary cytokine levels, correlating with positive treatment outcomes. Urinary cytokine changes may play a role to evaluate the mechanisms of action of various treatments in patients with IC/BPS.
Appendix
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Literature
1.
go back to reference Homma Y, Akiyama Y, Kim JH, Chuang YC, Jeong SJ, Meng E, Kitta T, Jhang JF, Furuta A, Lee KS, Maeda D (2024) Definition change and update of clinical guidelines for interstitial cystitis and bladder pain syndrome. Low Urin Tract Symptoms 16:e12532CrossRefPubMed Homma Y, Akiyama Y, Kim JH, Chuang YC, Jeong SJ, Meng E, Kitta T, Jhang JF, Furuta A, Lee KS, Maeda D (2024) Definition change and update of clinical guidelines for interstitial cystitis and bladder pain syndrome. Low Urin Tract Symptoms 16:e12532CrossRefPubMed
2.
go back to reference Shie JH, Kuo HC (2011) Higher levels of cell apoptosis and abnormal E-cadherin expression in the urothelium are associated with inflammation in patients with interstitial cystitis/painful bladder syndrome. BJU Int 108:E136–E141CrossRefPubMed Shie JH, Kuo HC (2011) Higher levels of cell apoptosis and abnormal E-cadherin expression in the urothelium are associated with inflammation in patients with interstitial cystitis/painful bladder syndrome. BJU Int 108:E136–E141CrossRefPubMed
3.
go back to reference Furuta A, Suzuki Y, Igarashi T, Koike Y, Kimura T, Egawa S, Yoshimura N (2019) Angiogenesis in bladder tissues is strongly correlated with urinary frequency and bladder pain in patients with interstitial cystitis/bladder pain syndrome. Int J Urol 26(Suppl 1):35–40CrossRefPubMed Furuta A, Suzuki Y, Igarashi T, Koike Y, Kimura T, Egawa S, Yoshimura N (2019) Angiogenesis in bladder tissues is strongly correlated with urinary frequency and bladder pain in patients with interstitial cystitis/bladder pain syndrome. Int J Urol 26(Suppl 1):35–40CrossRefPubMed
4.
go back to reference Teichman JM, Parsons CL (2007) Parsons, contemporary clinical presentation of interstitial cystitis. Urology 69(4 Suppl):41–47CrossRefPubMed Teichman JM, Parsons CL (2007) Parsons, contemporary clinical presentation of interstitial cystitis. Urology 69(4 Suppl):41–47CrossRefPubMed
5.
go back to reference Malde S, Palmisani S, AI-Kaisy A, Sahai A (2018) Guideline of guidelines: bladder pain syndrome. BJU Int 122:729–743CrossRefPubMed Malde S, Palmisani S, AI-Kaisy A, Sahai A (2018) Guideline of guidelines: bladder pain syndrome. BJU Int 122:729–743CrossRefPubMed
6.
go back to reference Clemens JQ, Erickson DR, Varela NP, Lai HH (2022) Diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol 208:34–42CrossRefPubMed Clemens JQ, Erickson DR, Varela NP, Lai HH (2022) Diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol 208:34–42CrossRefPubMed
7.
go back to reference Park JJ, Kim KT, Lee EJ, Chun J, Lee S, Shim SR, Kim JH (2024) Current updates relating to treatment for interstitial cystitis/bladder pain syndrome: systematic review and network meta-analysis. BMC Urol 24:95CrossRefPubMedPubMedCentral Park JJ, Kim KT, Lee EJ, Chun J, Lee S, Shim SR, Kim JH (2024) Current updates relating to treatment for interstitial cystitis/bladder pain syndrome: systematic review and network meta-analysis. BMC Urol 24:95CrossRefPubMedPubMedCentral
8.
go back to reference Jiang YH, Jhang JF, Hsu YH, Ho HC, Wu YH, Kuo HC (2020) Urine cytokines as biomarkers for diagnosing interstitial cystitis/bladder pain syndrome and mapping its clinical characteristics. Am J Physiol Renal Physiol 318:F1391–F1399CrossRefPubMed Jiang YH, Jhang JF, Hsu YH, Ho HC, Wu YH, Kuo HC (2020) Urine cytokines as biomarkers for diagnosing interstitial cystitis/bladder pain syndrome and mapping its clinical characteristics. Am J Physiol Renal Physiol 318:F1391–F1399CrossRefPubMed
9.
go back to reference Tyagi P, Barclay D, Zamora R, Yoshimura N, Peters K, Vodovotz Y, Chancellor M (2010) Urine cytokines suggest an inflammatory response in the overactive bladder: a pilot study. Int Urol Nephrol 42:629–635CrossRefPubMed Tyagi P, Barclay D, Zamora R, Yoshimura N, Peters K, Vodovotz Y, Chancellor M (2010) Urine cytokines suggest an inflammatory response in the overactive bladder: a pilot study. Int Urol Nephrol 42:629–635CrossRefPubMed
10.
go back to reference Kuo HC, Liu HT, Shie JH (2013) Potential urine and serum biomarkers for patients with overactive bladder and interstitial cystitis/bladder pain syndrome. Tzu Chi Med J 25:13–18CrossRef Kuo HC, Liu HT, Shie JH (2013) Potential urine and serum biomarkers for patients with overactive bladder and interstitial cystitis/bladder pain syndrome. Tzu Chi Med J 25:13–18CrossRef
11.
go back to reference Jiang YH, Jhanf JF, Hsu YH, Ho HC, Wu YH, Kuo HC (2021) Urine biomarkers in ESSIC type 2 interstitial cystitis/bladder pain syndrome and overactive bladder with developing a novel diagnostic algorithm. Sci Rep 11:914CrossRefPubMedPubMedCentral Jiang YH, Jhanf JF, Hsu YH, Ho HC, Wu YH, Kuo HC (2021) Urine biomarkers in ESSIC type 2 interstitial cystitis/bladder pain syndrome and overactive bladder with developing a novel diagnostic algorithm. Sci Rep 11:914CrossRefPubMedPubMedCentral
12.
go back to reference Yu WR, Jiang YH, Jhang JF, Kuo HC (2022) Use of urinary cytokine and chemokine levels for identifying bladder conditions and predicting treatment outcomes in patients with interstitial cystitis/bladder pain syndrome. Biomedicines 10:1149CrossRefPubMedPubMedCentral Yu WR, Jiang YH, Jhang JF, Kuo HC (2022) Use of urinary cytokine and chemokine levels for identifying bladder conditions and predicting treatment outcomes in patients with interstitial cystitis/bladder pain syndrome. Biomedicines 10:1149CrossRefPubMedPubMedCentral
13.
go back to reference Kuo HC, Jiang YH, Tsai YC, Kuo YC (2016) Intravesical botulinum toxin-A injections reduce bladder pain of interstitial cystitis/bladder pain syndrome refractory to conventional treatment—a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial. Neurourol Urodyn 35:609–614CrossRefPubMed Kuo HC, Jiang YH, Tsai YC, Kuo YC (2016) Intravesical botulinum toxin-A injections reduce bladder pain of interstitial cystitis/bladder pain syndrome refractory to conventional treatment—a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial. Neurourol Urodyn 35:609–614CrossRefPubMed
14.
go back to reference Chuang YC, Meng E, Chancellor M, Kuo HC (2020) Pain reduction realized with extracorporeal shock wave therapy for the treatment of symptoms associated with interstitial cystitis/bladder pain syndrome—a prospective, multicenter, randomized, double-blind, placebo-controlled study. Neurourol Urodyn 39:1505–1514CrossRefPubMed Chuang YC, Meng E, Chancellor M, Kuo HC (2020) Pain reduction realized with extracorporeal shock wave therapy for the treatment of symptoms associated with interstitial cystitis/bladder pain syndrome—a prospective, multicenter, randomized, double-blind, placebo-controlled study. Neurourol Urodyn 39:1505–1514CrossRefPubMed
15.
go back to reference Yu WR, Jiang YH, Jhang JF, Kuo HC (2025) Repeated intravesical injections of platelet-rich plasma are safe and effective in the treatment of interstitial cystitis/bladder pain syndrome. Tzu Chi Med J 37:72–79CrossRefPubMed Yu WR, Jiang YH, Jhang JF, Kuo HC (2025) Repeated intravesical injections of platelet-rich plasma are safe and effective in the treatment of interstitial cystitis/bladder pain syndrome. Tzu Chi Med J 37:72–79CrossRefPubMed
16.
go back to reference Hanno PM, Erickson D, Moldwin R, Faraday MM, AUA (2015) Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment. J Urol 193:1545–1553CrossRefPubMed Hanno PM, Erickson D, Moldwin R, Faraday MM, AUA (2015) Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment. J Urol 193:1545–1553CrossRefPubMed
17.
go back to reference Hanno P, Dmochowski R (2009) Status of international consensus on interstitial cystitis/bladder pain syndrome/painful bladder syndrome: 2008 snapshot. Neurourol Urodyn 28:274–286CrossRefPubMed Hanno P, Dmochowski R (2009) Status of international consensus on interstitial cystitis/bladder pain syndrome/painful bladder syndrome: 2008 snapshot. Neurourol Urodyn 28:274–286CrossRefPubMed
18.
go back to reference Morales A, Emerson L, Nickel JC, Lundie M (1996) Intravesical hyaluronic acid in the treatment of refractory interstitial cystitis. J Urol 156:45–48CrossRefPubMed Morales A, Emerson L, Nickel JC, Lundie M (1996) Intravesical hyaluronic acid in the treatment of refractory interstitial cystitis. J Urol 156:45–48CrossRefPubMed
19.
go back to reference Shie JH, Liu HT, Wang YS, Kuo HC (2013) Immunohistochemical evidence suggests repeated intravesical application of botulinum toxin A injections may improve treatment efficacy of interstitial cystitis/bladder pain syndrome. BJU Int 111:638–646CrossRefPubMed Shie JH, Liu HT, Wang YS, Kuo HC (2013) Immunohistochemical evidence suggests repeated intravesical application of botulinum toxin A injections may improve treatment efficacy of interstitial cystitis/bladder pain syndrome. BJU Int 111:638–646CrossRefPubMed
20.
go back to reference Lin CC, Huang YC, Lee WC, Chuang YC (2020) New frontiers of the treatment of interstitial cystitis/bladder pain syndrome - focused on stem cells, platelet-rich plasma, and low-energy shock wave. Int Neurourol J 24:211–221CrossRefPubMedPubMedCentral Lin CC, Huang YC, Lee WC, Chuang YC (2020) New frontiers of the treatment of interstitial cystitis/bladder pain syndrome - focused on stem cells, platelet-rich plasma, and low-energy shock wave. Int Neurourol J 24:211–221CrossRefPubMedPubMedCentral
21.
go back to reference Mormone E, Cistermino A, Capone L, Caradonna E, Sbarbati A (2024) The model of interstitial cystitis for evaluating new molecular strategies of interstitial regeneration in humans. Int J Mol Sci 25:2326CrossRefPubMedPubMedCentral Mormone E, Cistermino A, Capone L, Caradonna E, Sbarbati A (2024) The model of interstitial cystitis for evaluating new molecular strategies of interstitial regeneration in humans. Int J Mol Sci 25:2326CrossRefPubMedPubMedCentral
22.
go back to reference Jiang YH, Kuo YC, Jhang JF, Lee CL, Hsu YH, Ho HC, Kuo HC (2020) Repeated intravesical injections of platelet-rich plasma improve symptoms and alter urinary functional proteins in patients with refractory interstitial cystitis. Sci Rep 10:15218CrossRefPubMedPubMedCentral Jiang YH, Kuo YC, Jhang JF, Lee CL, Hsu YH, Ho HC, Kuo HC (2020) Repeated intravesical injections of platelet-rich plasma improve symptoms and alter urinary functional proteins in patients with refractory interstitial cystitis. Sci Rep 10:15218CrossRefPubMedPubMedCentral
23.
go back to reference Sukubo NG, Tibalt E, Respizzi S, Locati M, d’Agostino MC (2015) Effect of shock waves on macrophages: a possible role in tissue regeneration and remodeling. Int J Surg 24:124–130CrossRefPubMed Sukubo NG, Tibalt E, Respizzi S, Locati M, d’Agostino MC (2015) Effect of shock waves on macrophages: a possible role in tissue regeneration and remodeling. Int J Surg 24:124–130CrossRefPubMed
24.
go back to reference Everts P, Onishi K, Jayaram P, Lana JF, Mauthner K (2020) Platelet-rich plasma: new performance understandings and therapeutic considerations in 2020. Int J Mol Sci 21:7794CrossRefPubMedPubMedCentral Everts P, Onishi K, Jayaram P, Lana JF, Mauthner K (2020) Platelet-rich plasma: new performance understandings and therapeutic considerations in 2020. Int J Mol Sci 21:7794CrossRefPubMedPubMedCentral
25.
go back to reference Jhang JF, Jiang YH, Hsu YH, Ho HC, Birder LA, Lin TY, Kuo HC (2022) Improved urothelial cell proliferation, cytoskeleton and barrier function protein expression in the patients with interstitial cystitis/bladder pain syndrome after intravesical platelet-rich plasma injection. Int Neurourol J 26(Suppl 1):S57–S67CrossRefPubMedPubMedCentral Jhang JF, Jiang YH, Hsu YH, Ho HC, Birder LA, Lin TY, Kuo HC (2022) Improved urothelial cell proliferation, cytoskeleton and barrier function protein expression in the patients with interstitial cystitis/bladder pain syndrome after intravesical platelet-rich plasma injection. Int Neurourol J 26(Suppl 1):S57–S67CrossRefPubMedPubMedCentral
26.
go back to reference Teichman JMH, Moldwin R (2007) The role of the bladder surface in interstitial cystitis/painful bladder syndrome. Can J Urol 14:3599–3607PubMed Teichman JMH, Moldwin R (2007) The role of the bladder surface in interstitial cystitis/painful bladder syndrome. Can J Urol 14:3599–3607PubMed
27.
go back to reference Hurst RE, Rhodes SW, Adamson PB, Parsons CL, Roy JB (1987) Functional and structural characteristics of the glycosaminoglycans of the bladder luminal surface. J Urol 138:433–437CrossRefPubMed Hurst RE, Rhodes SW, Adamson PB, Parsons CL, Roy JB (1987) Functional and structural characteristics of the glycosaminoglycans of the bladder luminal surface. J Urol 138:433–437CrossRefPubMed
28.
go back to reference Chang YC, Lee YJ, Chueh JS, Chang SJ (2024) Glycosaminoglycan replacement therapy in preventing women’s recurrent urinary tract infections?: a systematic review and meta-analysis. Urol Sci 35:59–66CrossRef Chang YC, Lee YJ, Chueh JS, Chang SJ (2024) Glycosaminoglycan replacement therapy in preventing women’s recurrent urinary tract infections?: a systematic review and meta-analysis. Urol Sci 35:59–66CrossRef
29.
go back to reference Wu ZS, Lee WC, Chancellor MB, Wang HJ, Huang CC, Chuang YC (2024) Extracorporeal shock wave therapy modulates miRNA expression, reduces inflammation, and improves liposome retention in a rat model of cyclophosphamide-induced cystitis—experimental studies. Int J Surg 110:6869–6872CrossRefPubMedPubMedCentral Wu ZS, Lee WC, Chancellor MB, Wang HJ, Huang CC, Chuang YC (2024) Extracorporeal shock wave therapy modulates miRNA expression, reduces inflammation, and improves liposome retention in a rat model of cyclophosphamide-induced cystitis—experimental studies. Int J Surg 110:6869–6872CrossRefPubMedPubMedCentral
30.
go back to reference Lin HY, Lu JH, Chuang SM, Chueh KS, Juan TJ, Liu YC, Juan YS (2021) Urinary biomarkers in interstitial cystitis/bladder pain syndrome and its impact on therapeutic outcome. Diagnostics (Basel) 12:75CrossRefPubMedPubMedCentral Lin HY, Lu JH, Chuang SM, Chueh KS, Juan TJ, Liu YC, Juan YS (2021) Urinary biomarkers in interstitial cystitis/bladder pain syndrome and its impact on therapeutic outcome. Diagnostics (Basel) 12:75CrossRefPubMedPubMedCentral
31.
go back to reference Shen YC, Tyagi P, Lee WC, Chancellor MB, Chuang YC (2021) Improves symptoms and urinary biomarkers in refractory interstitial cystitis/bladder pain syndrome patients randomized to extracorporeal shock wave therapy versus placebo. Sci Rep 11:7558CrossRefPubMedPubMedCentral Shen YC, Tyagi P, Lee WC, Chancellor MB, Chuang YC (2021) Improves symptoms and urinary biomarkers in refractory interstitial cystitis/bladder pain syndrome patients randomized to extracorporeal shock wave therapy versus placebo. Sci Rep 11:7558CrossRefPubMedPubMedCentral
32.
go back to reference Kuo HC, Peng CW, Jiang YH, Jhang JF (2024) Urinary viral spectrum in patients with interstitial cystitis/bladder pain syndrome and the clinical efficacy of valacyclovir treatment. Biomedicines 12:522CrossRefPubMedPubMedCentral Kuo HC, Peng CW, Jiang YH, Jhang JF (2024) Urinary viral spectrum in patients with interstitial cystitis/bladder pain syndrome and the clinical efficacy of valacyclovir treatment. Biomedicines 12:522CrossRefPubMedPubMedCentral
33.
go back to reference Yu WR, Jiang YH, Jhang JF, Kuo HC (2024) Urine biomarker could be a useful tool for differential diagnosis of a lower urinary tract dysfunction. Tzu Chi Med J 36:110–119PubMed Yu WR, Jiang YH, Jhang JF, Kuo HC (2024) Urine biomarker could be a useful tool for differential diagnosis of a lower urinary tract dysfunction. Tzu Chi Med J 36:110–119PubMed
Metadata
Title
Revealing distinct treatment mechanisms and outcome correlations in patients with interstitial cystitis/bladder pain syndrome after different bladder therapies through urinary biomarker analysis
Authors
Yu-Chieh Chiu
Ping-Chiao Tsai
Jia-Fong Jhang
Hann-Chorng Kuo
Publication date
29-01-2025
Publisher
Springer Netherlands
Published in
International Urology and Nephrology
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-025-04388-3

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