Role of urinary cations in the etiology of interstitial cystitis: A multisite study

Abstract

Objective To determine whether patients with interstitial cystitis have elevated levels of toxic urinary cations, to identify and quantify these cationic metabolites, and to assess their cytotoxicity. Methods Isolation of cationic fraction was achieved by solid phase extraction using an Oasis MCX cartridge on urine specimens from interstitial cystitis patients and controls. C18 reverse phase high‐performance liquid chromatography was used to profile cationic metabolites, and they were quantified by the area under the peaks and normalized to creatinine. Major cationic fraction peaks were identified by reverse phase high‐performance liquid chromatography and liquid chromatography–mass spectrometry. HTB‐4 urothelial cells were used to determine the cytotoxicity of cationic fraction and of individual metabolites. Results The reverse phase high‐performance liquid chromatography analysis was carried out on cationic fraction metabolites isolated from urine samples of 70 interstitial cystitis patients and 34 controls. The mean for controls versus patients was 3.84 (standard error of the mean 0.20) versus 6.71 (0.37) mAU*min/µg creatinine, respectively (P = 0.0001). The cationic fraction cytotoxicity normalized to creatinine for controls versus patients in mean percentage was −7.79% (standard error of the mean 3.32%) versus 20.03% (standard error of the mean 2.75%; P < 0.0005). The major toxic cations were 1‐methyladenosine, 1‐methylguanine, N2,N2‐dimethylguanosine and L‐tryptophan. Conclusions These data confirm significant elevation of toxic cations in the urine of interstitial cystitis patients. These toxic cations likely represent a primary cause of interstitial cystitis, as they can injure the bladder mucus and initiate an epithelial leak.

Food Sensitivities in a Diverse Nationwide Cohort of Veterans With Interstitial Cystitis/Bladder Pain Syndrome

“…14 Parsons et al examined the effects of cations in urine and found that urine with higher levels of cations can damage the bladder's mucus and initiate an epithelial leak. 15 Furthermore, a review by Klumpp outlined another plausible theorydpelvic cross talk. 16 According to this theory, comestibles that evoke a response in the colon or surrounding organs could exacerbate the bladder- centric symptoms felt by IC/BPS patients.…”

Lower Urinary Tract Inflammation and Infection: Key Microbiological and Immunological Aspects

“…Pathophysiological changes resulting in altered bladder permeability represent a compelling theory for the origins of HIC. A recent multi-site study determined that patients with IC/BPS had significantly elevated levels of cationic toxins within their urine, though the study did not stratify by disease subtype [113]. Increased levels of cationic toxins can damage the bladder and increase permeability.…”

Current Understanding and Future Perspectives of Interstitial Cystitis/Bladder Pain Syndrome

“…Finally, although it is common knowledge that urine pH is influenced by diet and that acidic urine enhances bladder pain and frequent urination, diet modification therapy is often not vigorously enforced in IC/BPS patients [39]. Some studies have also reported that substances such as potassium and toxic cations in urine can modify lower urinary tract symptoms of IC/ BPS [40] and that various dietary factors including citrus fruits, tomatoes, spicy food, alcohol, and caffeinated beverages can trigger a flare (defined as urologic or pelvic pain that is much worse than usual) in IC/BPS patients [41]. Therefore, further research in this field of dietary modification is strongly recommended to improve the treatment of IC/BPS.…”