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Increased toxic urinary cations in males with interstitial cystitis: a possible cause of bladder symptoms

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Abstract

Purpose

To identify and quantify toxic urinary cations in male patients with bladder pain syndrome/interstitial cystitis versus male controls, to compare them in symptomatic patients to those significantly improved, and to evaluate cytotoxicity of these cations to cultured urothelial cells to determine whether Tamm-Horsfall protein (THP) can neutralize the cations.

Methods

Isolation of cationic fraction (CFs) was achieved by solid phase extraction on urine specimens of 51 male patients with IC and 33 male controls. C18 reverse-phase high-performance liquid chromatography was used to profile and quantify cationic metabolites. Major CF peaks were identified by liquid chromatography–tandem mass spectrometry. HTB-4 urothelial cells were used to determine the cytotoxicity of CFs, individual metabolites, and of metabolite mixture with THP of patient versus THP of control subject.

Results

CF content was significantly higher in patients compared to controls (p < 0.001). Patients had higher levels of modified nucleosides, amino acids, and their derivatives compared to controls. Cytotoxicity for control versus patient mean (SEM) percent was 1.7 (2.9) % versus 63.0 (3.7) %, respectively, (p < 0.001). Cytotoxicity of metabolites was reduced in the presence of THP of control compared to THP of patient (p < 0.001).

Conclusions

Patients with IC had significantly higher levels of cationic metabolites with higher cytotoxicity compared to controls. THP of these patients had reduced ability to sequester cytotoxicity of cationic metabolites. Patients who significantly improved on therapy had the same levels and toxicity of cationic metabolites as symptomatic males, suggesting that these cations may be the cause of epithelial dysfunction in IC.

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Authors and Affiliations

  1. Department of Urology, UC San Diego Health, 200 West Arbor Dr #8897, San Diego, CA, 92103-8897, USA

    Sulabha Argade, Zoltan Berecz & C. Lowell Parsons

  2. Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA

    Yongxuan Su

Authors
  1. Sulabha Argade
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  2. Zoltan Berecz
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  3. Yongxuan Su
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  4. C. Lowell Parsons
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Correspondence to C. Lowell Parsons.

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Argade, S., Berecz, Z., Su, Y. et al. Increased toxic urinary cations in males with interstitial cystitis: a possible cause of bladder symptoms. World J Urol 34, 1685–1691 (2016). https://doi.org/10.1007/s00345-016-1808-4

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  • DOI: https://doi.org/10.1007/s00345-016-1808-4

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