Elevated Plasma Histamine in Chronic Uremia Effects of Ketotifen on Pruritus

Abstract

Abstract: A role for histamine in the pathogenesis of uremic pruritus was investigated in maintenance hemodialysis patients. Venous plasma histamine levels, as determined by radioenzymatic assay, were significantly higher (p < 0.05) in hemodialysis patients with pruritus (368 ± 103 pg/ml [mean ± SEM], n = 6) than in those without pruritus (146 ± 22 pg/ml, n = 5) and in normal controls (142 ± 16, n = 5). Arteriovenous fistula histamine levels (202 ± 52 pg/ml, n = 6) were significantly lower (p < 0.05) than simultaneously drawn venous samples. Markedly elevated histamine‐degrading enzyme (histaminase) activities were found in both hemodialysis patients with (2.95 ± 0.18 pg histamine degraded/minute) and without (2.44 ± 0.28) pruritus, but was undetectable in normal controls. Histaminase activities did not significantly differ in simultaneously drawn venous and fistula samples. With hemodialysis, histaminase activities fell significantly (p < 0.01), whereas plasma histamine did not change. We further examined the effects of ketotifen, a putative mast cell stabilizer, on severe uremic pruritus. Five of five patients had significant (p <0.01) reductions in pruritus, as judged on a six‐point pruritus index, after 8 weeks of drug (x = 2.3), as compared to conventional therapy (x = 5.9). Despite these improvements, no significant differences were noted in pre‐ versus post‐drug plasma histamine levels, histaminase activities, or the histamine content per gram of skin biopsy specimen. These data support prior hypotheses that mast cell activation contributes to the pruritus of uremia. Copyright © 1991, Wiley Blackwell. All rights reserved