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 less than 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 less than 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 less than 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 less than 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.