1866 URINARY POTASSIUM IN

APPENDIX: SYMPTOM GRADING SCALE

Potassium protocol Subjects are told to consider their symptoms at the start as

baseline of 0. ARer instilling the solution for 2 to 3 minutes, ask the patient if it provokes their symptoms on a scale of 1 to 5. Then ask the patient to compare solution 1 with solution 2 and answer the 2 questions. If they believe that solution 2 is worse, then the test is positive.

Pain 0 (None), 1 (Mild), 2 to 3 (Moderate), 4 to 5 (Severe) Urgency 0 (None), 1 (Mild), 2 to 3 (Moderate), 4 to 5

Questions 1. Which symptom is worse? Solution 1, Solution

2. Is the difference between solutions: None, Mild, Moder-

(Severe)

2, Neither

ate, Severe

REFERENCES

1. Parsons, C. L., Stein, P. C., Bidair, M. and Lebow, D.: Abnormal sensitivity to intravesical potassium in interstitial cystitis and radiation cystitis. Neurourol. Umdynam., 13 515, 1994.

2. Teichman, J. M. H., Nielsen-Omeis, B. J. and McIver, B. D.: Modified urodynamics for interstitial cystitis. J. Urol., part 2, 1 6 5 4334 abstract 491, 1996.

3. Payne, C. K. and Browning, S.: Graded potassium chloride test- ing in interstitial cystitis. J. Urol., part 2, 1 6 5 4384 abstract 511,1996.

4. Parsons, C. L., Lilly, J. D. and Stein, P.: Epithelial dysfunction in nonbacterial cystitis (interstitial cystitis). J. Urol., 145: 732, 1991.

5. Lilly, J. D. and Parsons, C. L.: Bladder surface glycosaminogly- cans is a human epithelial permeability barrier. Surg. Gynec. Obst., 171: 493, 1990.

6. Parsons, C. L., Boychuk, D., Jones, S., Hurst, R. and Callahan, H.: Bladder surface glycosaminoglycans: an epithelial perme- ability barrier. J . Urol., 143: 139, 1990.

7. Parsons, C. L., S t a a e r , C. and Schmidt, J. D.: Bladder-surface glycosaminoglycans: an efficient mechanism of environmental adaptation. Science, 208: 605, 1980.

8. Parsons, C. L., Greenspan, C. and Mulholland, S. G.: The pri- mary antibacterial defense mechanism of the bladder. Invest. Urol., 13 72, 1975.

9. Parsons, C. L., Greenspan, C., Moore, S. W. and Mulholland, S. G.: Role of surface mucin in primary antibacterial defense of bladder. Urology, 9 48, 1977.

10. Gill, W. B., Jones, K. W. and Ruggiero, K. J.: Protective effects of heparin and other sulfated glycosaminoglycans on crystal ad- hesion to injured urothelium. J. Urol., 127: 152, 1982.

11. Chelsky, M. J., h e n , S. I., Knight, L. C., Maurer, A. H., Hanno, P. M. and Ruggieri, M. R.: Bladder permeability in interstitial cystitis is similar to that of normal volunteers: direct meas- urement by transvesical absorption of b h n e t i u m - diethylenetriaminepentaacetic acid. J. Urol., 151: 346,1994.

12. Parsons, C. L.: Epithelial coating techniques in the treatment of interstitial cystitis. Urology, suppl., 4 9 100, 1997.

13. Hohlbrugger, G. and Lentsch, P.: Intravesical ions, osmolality and pH influence the volume pressure response in the normal rat bladder, and this is more pronounced after DMSO expo- sure. Eur. Urol., 11: 127, 1985.

14. Hohlbrugger, G.: The vesical blood-urine barrier: a relevant and dynamic interface between renal function and nervous bladder control. J. Urol., lbl: 6, 1995.

15. Mulholland, S. G., Hanno, P., Parsons, C. L., Sant, G. R. and Staskin, D. R.: Pentosan polysulfate sodium for therapy of interstitial cystitis. A double-blind, placebo-controlled clinical study. Urology, 35: 552,1990.

16. Fritjofsson, A., Fall, M., Juhlin, R., Persson, B. E. and Ruutu, M.: Treatment of ulcer and nonulcer interstitial cystitis with so- dium pentosanpolysulfate: a multi-center trial. J. Urol., 138 508, 1987.

17. Holm-Bentzen, M., Jacobsen, F., Nerstrom, B., Lose, G., Kristensen, J . K., Pederson, R. H., Krarup, T. Feggetter, J., Bates, P.., Barnard, R., Larsen, S. and Hald, T.: A prospective double-blind clinically controlled multi-center trial of sodium pentosanpolysulfate in the treatment of interstitial cystitis and related painful bladder disease. J. Urol., 1 3 8 503, 1987.

18. Parsons, C. L., Housley, T., Schmidt, J. D. and LeBow, D.:

INTERSTITIAL CYSTITIS

Treatment of interstitial cystit& with intravesical heparin. Brit. J. Urol., 73: 504, 1994.

19. Parsons, C. L., Benson, G., C u b , S. J., Hanno, P., Sant, G. R. and Webster, G.: A quantitatively controlled method to study prospectively interstitial cystitis and demonstrate the efficacy of pentosanpolysulfate. J. Urol., 1M): 845, 1993.

20. Oravisto, K. J., ARhan, 0. S. and Jokinen, E. J.: Interstitial cystitis. Clinical and immunological findings. Scand. J. Urol. Nephrol., 4 37, 1970.

21. Hanash, K. A. and Pool, T. L.: Interstitial and hemorrhagic cystitis: viral, bacterial and fungal studies. J . Urol., 104: 7056,1970.

22. Oravisto, K. J. and Alfthan, 0. S.: Treatment of interstitial cystitis with immunosuppression and chloroquine derivatives. Eur. Urol., 2 82, 1976.

23. Silk, M. R.: Bladder antibodies in interstitial cystitis. J. Urol., 103: 307, 1970.

24. Holm-Bentzen, J . and Lose, G.: Pathology and pathogenesis of interstitial cystitis. Urology, suppl. 4, 29 8, 1987.

25. Oravisto, K. J.: Interstitial cystitis as an autoimmune disease. A review. Eur. Urol., 6: 10, 1980.

26. Weaver, R. G., Dougherty, T. F. and Natoli, C. A.: Recent con- cepts of interstitial cystitis. J. Urol., 89 377, 1963.

27. Lotz, M., Villiger, P., Hugli, T., Koziol, J. and Zuraw, B. L.: Interleukin-6 and interstitial cystitis. J . Urol., 1 6 2 869, 1994.

28. Nigro, D. A, Wein, k J., Foy, M., Parsons, C. L., Williams, M., Nyberg, L. M., Jr., Landis, J. R., Matthew Cook, Y. L. and Simon, L. J.: Associations among cystoscopic and urodynamic findings for women enrolled in the Interstitial Cystitis Data Base (ICDB) Study. Urology, suppl., 4 9 86, 1997.

EDITORIAL COMMENT

These authors are to be congratulated on a thoughtful and com- prehensive discussion of an innovative hypothesis regarding potas- sium and its role in the leaky epithelium theory of the etiology of interstitial cystitis, which they have ably championed. The data show a hypersensitivity to intravesical potassium in 75% of intersti- tial cystitis patients, 100% with acute urinary infection and 25% with detrusor instability. Controls and patients with bladder outlet obstruction were unlikely to respond. Our study also demonstrated some increased pain sensitivity to potassium chloride in interstitial cystitis patients but controls were just as likely to tell the difference between potassium chloride and sodium chloride placed in the blad- der.’

For the clinician distinguishing BPH and bladder outlet obstruc- tion from interstitial cystitis is not generally a problem, and the usefulness of this test as diagnostic for interstitial cystitis remains to be proved. By the data presented 25% of interstitial cystitis patients are not sensitive to potassium chloride and 25% with detrusor insta- bility are sensitive. Patients with motor urgency may sometimes be difficult to separate from those with pure sensory urgency, and the usefulness of the test in this group does not seem to be high. A cystometrogram would be just as simple.

Since it is known that normal bladder epithelium is never abso- lutely tight and there is always some leak, however small.2 it is conceivable that the findings of pain with potassium chloride are related to hypersensitivity of the sensory nerves in this condition rather than to pathological epithelial permeability, a t least in some patients. The accompanying protamine treated control study and resulting potassium absorption are intriguing and suggestive of in- creased potassium absorption in interstitial cystitis patients but these data by no means confirm this theory. Protamine is known to damage the epithelium but whether this injury duplicates intersti- tial cystitis is uncertain.

Ultimately the question is how we use the novel information pro- vided by these authors. As the article suggests, interstitial cystitis remains a clinical syndrome regardless of how we try to devise diagnostic tests. Frequency and pain unrelated to other known causes are by definition interstitial cystitis. As other causes of fre- quency and pain are determined, the world of interstitial cystitis will decrease, much as the urethral syndrome has begun to disappear as a diagnosis as its many infectious causes have been determined. I think that the test may prove useful when we have more data in regard to its ability to categorize patients successfully for treatment. As treatment becomes less empirical, patients will note therapeutic benefits sooner. I anxiously await the future studies of this group in

’

I

URINARY POTASSIUM IN INTERSTITIAL CYSTITIS 1867

regard to the results of using this test to stratify patients for therapy compared to a control group.

Philip M. Hanno Department of Urology Temple University Hospital Philadelphia, Pennsylvania

1. Roberto, P. J., Reich, J. D., Hirshberg, S., Knight, L., Hanno, P. M. and Ruggieri, M.: hsessment of bladder permeability and sensation in interstitial cystitis patients. J. Urol., part 2, 157: 317, abstract 1235, 1997.

2. Hohlbrugger, G.: Disintegrity of the vesicle blood-urine barrier in interstitial cystitis: a viscious circle. In: Interstitial Cystitis. Edited by G. R. Sant. Philadelphia: Lippincott-Raven Publish- ers, 1997.

REPLY BY AUTHORS

We would respectively disagree with the interpretation of the study that he and his co-authors reported at the American Urological Association. They, in fact, got data identical to ours in that patients had a significantly greater sensitivity to potassium than sodium when quantified by an analogue pain scale. Their responses to po- tassium were also significantly greater in the interstitial cystitis than for the control group which is also the same as what we have reported. Hanno et al also claimed that normals were able to deter- mine potassium from sodium with the inference that this refutes our concepts. However, these findings likewise fit well with our hypoth- eses. They use such a large unphysiological concentration of potas-

sium that even a 3% absorption would be more than sufficient for sensory nerves to be depolarized so that subjects should be able to tell the difference between the 2 solutions. (We presume the differ- ence was that potassium caused some urgency while sodium did not.) The key is not being able to tell the difference but to quanbfy the responses as with an analogue pain or urgency scale because the potassium induces much more of a reaction.

We believe that our resulta for the interstitial cystitis and normal studies are best explained by altered epithelial permeability and not abnormal nerve sensitivity. We think that we provided good data to support this in tables 2 and 3 which show that normals with an intact epithelium have no absorption of potassium and no significant urgency but after mucus destruction there is a significant increase in absorption and sensory responses, both of which are reversed by heparin. These observations may best be explained by the hypothesis that we propose that the altered epithelial permeability to potassium resulta in secondary nerve depolarization producing symptoms espe- cially since sodium (table 5) did not provoke this response in normals after protamine treatment.

In reference to the commentary on BPH, we believe that the presence of potassium sensitivity in patients symptomatic for blad- der outlet obstruction readily separates the difference between motor and sensory urgency making this relatively simple test helpful to the clinician. When it is abnormal, it means there is a problem with potassium diffiion.

In summary, we believe that the best explanation of the total data is presented in the hypothesis we propose, that is altered epithelial permeability results in potassium diffusion, provocation of nerves (up regulation 7), and chronic injury and destruction of tissue from the toxic levels of this cation resulting in disease progression.