The role of urinary potassium in the pathogenesis and diagnosis of interstitial cystitis.
OBJECTIVE
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.


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.
Parsons
C L
CL
Division of Urology, University of California San Diego Medical Center, 92103-8897, USA.
Greenberger
M
M
Gabal
L
L
Bidair
M
M
Barme
G
G
D000328:Adult; D018856:Cystitis, Interstitial / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D003558:Cystoscopy; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011189:Potassium Chloride / Q000493:pharmacokinetics / Q000494:pharmacology; D011237:Predictive Value of Tests; D011470:Prostatic Hyperplasia / Q000503:physiopathology; D012021:Reflex, Abnormal; D012965:Sodium Chloride / Q000493:pharmacokinetics / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism; D014563:Urodynamics; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism
D012965:Sodium Chloride; D011189:Potassium Chloride