HISTAMINE AND SEROTONIN IN UREMIC PRURITUS - EFFECT OF ONDANSETRON INCAPD-PRURITIC PATIENTS

Pruritus is a common, unpleasant symptom of uremic patients. Serotonin and histamine have been reported as possible mediators of uremic prur itus, and ondansetron is a potent and selective inhibitor of 5-HT3 rec eptors. The aims of our study were (1) to evaluate the effect of ondan setron on uremic pruritus in continuous ambulatory peritoneal dialysis (CAPD) patients and its safety and (2) to investigate the role of his tamine and serotonin in uremic pruritus. To study the prevalence and p athogenesis of uremic pruritus, CAPD and hemodialysis (HD) patients we re asked to complete a pruritus questionnaire. The replies were scored based on numerical scales, and the results were evaluated by the same investigator who did not know the patients. Pruritus was graded, acco rding to the total points for each patient, as mild, moderate, or seve re. Of 54 patients on HD, 29 (53.7%) had pruritus, and of 43 patients on CAPD, pruritus was present in 21 (48.8%). In HD patients, pruritus was mild in 14 (48.3%), moderate in 12 (41.4%), and severe in 3 (10.3% ) patients; the distribution in CAPD patients was 9 (42.9%), 10 (47.6% ), and 2 (9.5%), respectively. There was no correlation between the pr esence and severity of pruritus and age, sex, primary renal disease, d uration of dialysis, dialysis solutions used, and hematological and bi ochemical parameters except for serum histamine and serotonin levels a nd their product. Plasma histamine levels in CAPD patients were 13.1 /- 1.1 ng/ml in pruritic and 11.0 +/- 3.9 ng/ml in nonpruritic patient s (p = 0.06), serum serotonin levels were 115.6 +/- 43.3 ng/ml and 64 +/- 42.3 ng/ml (p < 0.05), respectively, and the histamine x serotonin product was 1,461 +/- 576 and 646 +/- 545 (p < 0.01), respectively. E leven CAPD patients (6 males, 5 females) with a mean age of 66 (range 33-83) years and an average time on CAPD of 18 (range 3-31) months wit h moderate to severe pruritus were treated with ondansetron (4 mg twic e daily p.o.) for a mean period of 3 (range 1-5) months. All patients responded to the treatment. There was a significant reduction of the s everity of pruritus from the start of treatment, and on the 3rd day th e pruritic score (mean value) was 10 (range 5-19) points, while at tim e 0 (before treatment) it was 26 (range 19-37) points (p < 0.0001). Pr uritus disappeared in 7 patients at the end of the 1st week and in all patients at the end of the 2nd week of treatment. This effect was mai ntained during the study. Plasma histamine levels decreased significan tly during the treatment from 12.9 +/- 1.2 to 6.7 +/- 5.9 ng/ml (p < 0 .05). Also, serum serotonin levels were reduced from 125.1 +/- 47.8 to 59.3 +/- 27.5 ng/ml (p < 0.05) at the end of the 1st month of treatme nt, and the histamine x serotonin product showed a more significant re duction: from 1,544 +/- 656 to 454 +/- 436 (p < 0.01). Three patients reported an improvement in their nausea and vomiting during the treatm ent. Weekly clinical and laboratory examinations showed no side effect s, adverse reactions, or other complications. Our data indicate that o ndansetron is an effective, safe, and well-tolerated drug for the trea tment of uremic pruritus in CAPD patients and that histamine and serot onin may have a crucial role in the appearance or perception of the ur emic pruritus.