The Intravesical Potassium Sensitivity Test and Urodynamics: Implications in a Large Cohort of Patients with Lower Urinary Tract Symptoms

PURPOSE: Bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH) is the most common diagnosis in older men with lower urinary tract symptoms. However, these symptoms also can occur with interstitial cystitis. We determine whether the potassium sensitivity test is useful for distinguishing BPH from possible intersitial cystitis in patients with lower urinary tract symptoms. We also test the hypothesis that patients with these symptoms who have a positive test will have urodynamic findings consistent with the diagnosis of interstitial cystitis. MATERIALS AND METHODS: The potassium sensitivity test was performed in 526 (95%) males and 25 (5%) females with lower urinary tract symptoms undergoing urodynamic testing. Urodynamic parameters in the positive and negative potassium sensitivity test groups were compared. %Results: Of the patients 16% (89 of 551) had a positive potassium sensitivity test. Compared with patients who had a negative test, those who had a positive test were younger (61 versus 64 years, p = 0.03), had urgency at significantly lower volumes (108 versus 182 cc, p <0.0001), lower bladder capacity (343 versus 436 cc, p <0.0001) and lower post-void residual (49 versus 95 cc, respectively, p <0.001). Urodynamic parameters in the 24% (6 of 25) of women who had a positive potassium sensitivity test were similar to those in men who also had a positive test. CONCLUSIONS: Urodynamic findings in patients with lower urinary tract symptoms who have a positive potassium sensitivity test are significantly different from those in patients who have a negative test, and are similar to those findings characteristic of interstitial cystitis. Interstitial cystitis should be considered in patients with lower urinary tract symptoms who have a positive test. The potassium sensitivity and urodynamic tests may be a useful combination for screening men with lower urinary tract symptoms to identify those symptoms that may be due to interstitial cystitis versus BPH.     

THE ROLE OF URINARY POTASSIUM IN THE PATHOGENESIS AND DIAGNOSIS OF INTERSTITIAL CYSTITIS

Purpose

We determined whether intravesical potassium absorption in normal bladders correlates with increased sensory urgency, and corroborated the hypothesis that mucus is important in the regulation of epithelial permeability. We compared sensory nerve provocative ability of sodium versus potassium, and determined whether intravesical potassium sensitivity discriminates patients with interstitial cystitis from normal subjects and those with other sensory disorders of the bladder.

Materials and Methods

A total of 231 patients with interstitial cystitis and 41 normal subjects underwent intravesical challenge with 40 ml. water and then 40 ml. of 40 mEq./100 ml. potassium chloride. Subjective responses of urgency or pain stimulation were recorded on a scale of 0 to 5. In 19 normal subjects potassium absorption was measured at baseline, after injury of the bladder mucus with protamine, after heparin treatment to reverse mucus damage and then for a final time. These subjects simultaneously recorded the symptoms of sensory urgency and pain at baseline, after protamine and after heparin. Another group of normal volunteers underwent a challenge with sodium versus potassium to determine which cation was more provocative. Patients with bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH), detrusor instability, and acute and chronic urinary tract infection but no current infection were also evaluated for potassium sensitivity.

Results

Neither normal subjects nor patients with interstitial cystitis reacted to water administered intravesically. There was marked sensitivity to intravesical potassium in 75% of patients with interstitial cystitis versus 4% of controls (p <0.01). Only 1 patient with BPH responded to potassium and none of the 5 with chronic urinary tract infection responded. All 4 patients (100%) with a current acute urinary tract infection reacted positively to the potassium challenge. Of 16 patients with detrusor instability 25% responded. Normal subjects had minimal sensitivity to potassium before (11%) and markedly increased sensitivity after (79%) protamine treatment, and these symptoms were reversed by heparin in 42%. Potassium absorption directly correlated with symptoms (0.4, 3.0 and 1.3 mEq. before and after protamine, and after heparin reversal, respectively). In regard to sodium versus potassium provocation, potassium was far more provocative for causing urgency after protamine (10 versus 90%). Neither group underwent provocation before protamine.

Conclusions

Chronic diffusion of urinary potassium into the bladder interstitium may induce sensory symptoms, damage tissue and be a major toxic factor in the pathogenesis of interstitial cystitis. Intravesical potassium sensitivity is a reliable method for detecting abnormal epithelial permeability. It discriminates between patients with interstitial cystitis and normal subjects with intact epithelial function, and it is a useful diagnostic test for interstitial cystitis. Potassium sensitivity correlates with increased potassium absorption in normal subjects, and potassium is far more provocative than sodium. Potassium sensitivity is also present in acute urinary tract infection and occasionally detrusor instability but not in BPH or chronic urinary tract infections.     

Quantifying symptoms in men with interstitial cystitis/prostatitis, and its correlation with potassium-sensitivity testing

OBJECTIVE: To determine whether men previously diagnosed with prostatitis also have pathology originating in the bladder. PATIENTS, SUBJECTS AND METHODS: We administered the pelvic pain and urgency/frequency (PUF) questionnaire and the potassium-sensitivity test (PST) to 50 patients with prostatitis presenting in urological and primary care, and to 14 controls. In a separate control group of 22 men, the urethra was irrigated with KCl or NaCl (11 each) before and after experimental injury of the urethral mucosa. RESULTS: All 50 patients with prostatitis had PUF scores of > or = 7; 77% were positive for the PST. All 14 controls had PUF scores of 1 or 0 and a negative PST. In the urethral irrigation study in controls, KCl but not NaCl provoked urethral pain after mucosal injury. Before injury, neither KCl nor NaCl caused symptoms. CONCLUSION: The high rate of positive PST in patients with "classic" prostatitis indicates that pathology originating in the bladder may be an important source of symptoms in most. In patients with prostatitis and female patients with interstitial cystitis, symptoms may arise not from separate disease entities but from a continuum of epithelial dysfunction and potassium cycling that may be present throughout the lower urinary tract.     

Intravesical potassium chloride sensitivity test in men with chronic pelvic pain syndrome

PURPOSE: Intravesical potassium chloride has been reported to cause pain in patients with interstitial cystitis and male chronic prostatitis (CP)/chronic pelvic pain syndrome (CPPS). We performed the potassium chloride sensitivity test (PST) in subjects with CP/CPPS and healthy men without pelvic pain. MATERIALS AND METHODS: We recruited 40 men with CP/CPPS and 63 healthy men. The National Institutes of Health CPPS symptom index was used to measure the severity of symptoms. We instilled 100 ml physiological saline (NaCl 0.9%) intravesically. The bladder was emptied and 100 ml potassium chloride solution (KCl 40 mEq) were instilled. The subjects were asked to score urgency (0 to 10) and pain (0 to 10) sensations after each instillation. A positive PST was defined by 5 different cut-off points as the difference in score between KCl and NaCl instillations. Logistic regression analyses and area under the receiver operating characteristics curve were used to determine the predictive power of PST in CP/CPPS. RESULTS: There was no difference in pain and urgency scores between the men with CP/CPPS and controls (p >0.05 for each). Men with CP/CPPS had higher pain and urgency scores with KCl than with NaCl (p = 0.011 and 0.033, respectively). The rates of positive PST were 50% and 36.5% in the CP/CPPS and control groups, respectively (p = 0.160). There was no significant correlation of potassium chloride sensitivity scores with National Institutes of Health symptom scores (p >0.05 for each). The sensitivity, specificity, and positive predictive and negative predictive values of PST were 50%, 63.5%, 46.5% and 66.7%, respectively. CONCLUSIONS: Although there was a significant increase in pain and urgency scores following KCl instillation in patients with CP/CPPS, these scores and the rate of positive PST were not statistically different from those of healthy subjects. Thus, PST does not have a good predictive value in the diagnosis of CP/CPPS.     

The role of a leaky epithelium and potassium in the generation of bladder symptoms in interstitial cystitis/overactive bladder, urethral syndrome, prostatitis and gynaecological chronic pelvic pain

The traditional diagnosis of interstitial cystitis (IC) only recognizes the severe form of the disease. The far more common early and intermittent phases of the disease are not perceived to be part of IC but rather are misdiagnosed as urinary tract infection, urethral syndrome, overactive bladder, chronic prostatitis, urethritis, or a type of gynecologic pelvic pain (such as endometriosis, vulvodynia, or some type of vaginitis). All of these patient groups actually suffer from the same bladder disease. This disease results from a leaky bladder epithelium and subsequent potassium leakage into the bladder interstitium that generates the symptoms of frequency, urgency, pain or incontinence in any combination. Robust scientific data now support this important concept. These data will be reviewed herein. The conclusions derived from these data substantially alter the paradigms for urology and gynecology in the generation of frequency, urgency and pelvic pain. All the above-mentioned syndromes unite into one primary disease process, lower urinary dysfunction epithelium, or LUDE disease, and not the 10 plus syndromes traditionally recognized.     

HOW DO PATIENTS WITH INTERSTITIAL CYSTITIS PRESENT?

PURPOSE: We determined how interstitial cystitis progresses from initial symptoms to diagnosis. MATERIALS AND METHODS: We retrospectively analyzed the records of 45 patients to determine the dates of symptom onset and diagnosis, and sequence of urgency/frequency, nocturia and pain. We also documented alternate and previous diagnoses, and previous surgical treatments. RESULTS: Of the patients 89% presented with only 1 symptom. Median time from the initial symptom to all symptoms was 2 years (mean 5.5). The most common previous diagnoses were urinary infection in 19 cases, a gynecologic diagnosis in 14 and urethral diagnoses in 6. A previous urinary infection was documented in only 1 of 19 patients, while 11 had undergone hysterectomy and 5 diagnosed with endometriosis had no pathological documentation available. CONCLUSIONS: Early interstitial cystitis presents variably and usually with only a single symptom of urgency/frequency, nocturia or pain. Clinicians may fail to appreciate the symptoms of early interstitial cystitis, which leads to delayed diagnosis until the patient is more symptomatic. With time multiple symptoms manifest. Bacterial cystitis, prostatitis, endometriosis and chronic pelvic pain are common initial misdiagnoses. Interstitial cystitis should be considered when laboratory documentation of alternate diagnoses is lacking or when patients fail to respond to therapy for alternate diagnoses.     

Evaluation of intravesical potassium sensitivity test and bladder biopsy in patients with chronic prostatitis/chronic pelvic pain syndrome

AIM: We evaluated the possibility that patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) might have similar histological and physiological bladder changes as that documented in patients with painful bladder syndrome/interstitial cystitis (PBS/IC). METHODS: Thirty-five known patients of CP/CPPS according to the clinical criteria of National Institutes of Health (NIH) were evaluated. The severity of the symptoms was evaluated according the NIH-Chronic Prostatitis Symptom Index. All patients underwent a potassium sensitivity test (PST) and bladder cystoscopy. Bladder biopsy was obtained from 17 patients with prostatitis and four control patients. RESULTS: Urinary symptoms were present in 31 (88.6%) patients. Pelvic pain was reported in all patients. PST was positive in 26 (84%) of 31 patients that presented with urinary symptoms in its filling phase. In the voiding phase, 10 (28.5%) patients experienced urethral pain. Of these patients, five had negative filling PST. There were only two (5.7%) patients that had negative PST in both of its phases for an overall positive PST rate of 94.3%. The severity of PST was not correlated with the total symptom score (P = 0.37). However, patients with severe urinary symptoms were more likely to score higher grades with PST (P = 0.01). Of the 17 patients who underwent bladder biopsy, a significant increase in the number of mast cells (MC) was present in 11 (64.7%) patients. Glomerulations with bladder cystoscopy was observed in 24 (68.6%) patients. CONCLUSIONS: The data of the present study support the opinion that PBS/IC is under-diagnosed in male patients that present with urgency, frequency and/or pain. In some patients diagnosed as CP/CPPS, the symptoms might be related to bladder dysfunction rather than prostatic inflammation.     

A referral center's experience with transitional cell carcinoma misdiagnosed as interstitial cystitis

PURPOSE: There has been a recent trend to diagnose interstitial cystitis (IC) in a noninvasive way using a potassium sensitivity test, and a pelvic pain, urgency and frequency questionnaire. The concern is that significant pathology causing the bladder symptoms may be missed, such as transitional cell carcinoma. We present our experience with patients "labeled" as having IC who truly had cancer as the cause of irritative symptoms. MATERIALS AND METHODS: A retrospective review of patient records at our IC center was performed from 1998 to 2002. A total of 600 patients were seen at that time with the diagnosis of interstitial cystitis. RESULTS: Six patients (1%) previously diagnosed as having IC were found to have transitional cell carcinoma as the cause of symptoms, 4 of whom (67%) had no hematuria. Mean time from the diagnosis of IC to diagnosis of transitional cell carcinoma was 29.8 months. Irritative bladder symptoms resolved after identifying and treating the malignancy. CONCLUSIONS: Patients with irritative voiding symptoms require a thorough evaluation which may include cystoscopy, cytology and upper tract imaging. Hematuria was not a good predictor of cancer in our series. In the era before widespread use of minimally invasive means to diagnose IC (ie potassium sensitivity test, pelvic pain, urgency and frequency questionnaire) 1% of patients who were considered to have IC actually had transitional cell cancer as the cause of symptoms. One would expect that this number would increase if the criteria to diagnose IC and initiate treatment were oversimplified. Interstitial cystitis remains a diagnosis of exclusion.     

Interstitial cystitis: a guide to recognition, evaluation, and management for nurse practitioners.

Interstitial cystitis (IC) is a chronic disorder of unknown etiology that affects the lower urinary tract of up to 500,000 women and men in the United States. It is characterized by bladder and pelvic pain that varies from moderate discomfort to severe, debilitating pain and related lower urinary tract symptoms including nocturia, diurnal urinary frequency, and urgency. Because the symptoms of IC superficially resemble a urinary tract infection, it is often misdiagnosed and may remain so for months or even years. This article discusses the clinical manifestations of IC, including its differentiation from acute or recurring bacterial cystitis. Options for managing this significant and often debilitating voiding dysfunction are also discussed.     

Sexual dysfunction in the patient with prostatitis

Prostatitis (chronic prostatitis/chronic pelvic pain syndrome [CP/CPPS]) is a common condition in men that accounts for a significant number of visits to a medical doctor or urologist. It is one of the most widely diagnosed conditions in men who attend urologic clinics. Erectile dysfunction, defined as the consistent inability to obtain and/or maintain a penile erection sufficient for adequate sexual relations, also is a common problem. This review explores the links between sexual dysfunction and prostatitis. Most of the data linking lower urinary tract symptoms and erectile dysfunction suggest that lower urinary tract symptoms impair the overall quality of life and that a low quality of life contributes to or causes erectile dysfunction. Prostatitis-like symptoms such as perineal, penile, and suprapubic discomfort or pain during or after ejaculation and voiding complaints such as irritative and obstructive voiding symptoms (urinary frequency, urgency, and dysuria) may affect the global emotional well-being of a man. Erectile dysfunction also is strongly associated with a negative impact on the quality of life. The available literature demonstrating the influence of CP/CPPS on the incidence of erectile dysfunction is scant. From the literature, it is known that lower urinary tract symptoms and benign prostatic hyperplasia are definitely related to erectile dysfunction. Any kind of pain is likely to be the most significant symptom in men with CP/CPPS as it relates to sexual dysfunction. Sexual dysfunction such as ejaculation discomfort is described as a symptom of CP/CPPS. Most of the data linking the two suggest that CP/CPPS impairs the overall quality of life and it is this that contributes to or causes erectile dysfunction.