Uremic neurotoxin in the middle molecular weight range.
Among the middle molecule fractions obtained by high performance gel chromatography on Sephadex G-15  combined with gradient ion exchange chromatography on DEAE Sephadex A-25 from plasma ultrafiltrates of six polyneuropathic patients, only peak b4-2 was at a significantly higher concentration than that obtained from uremic patients with neuropathy. Purification of the b4-2 solute allows its quantitative determination in biological fluids. The b4-2 plasma concentrations are 1 mg/L in healthy subjects (n=30), 4.6 +/- 0.2 mg/L in uremic patients (n=67) and 13-19 mg/L in six polyneuropathic patients. The 24-hr urinary excretion is 13 +/- 1 mg. The weekly removal rates in hemofiltration or in hemodialysis, using high permeability membrane three times a week, are 38-40 mg. In an in vitro sural nerve test for the evalution of middle molecule neurotoxicity, the b4-2 solute exhibits a neurotoxic effect at concentrations similar to those found in plasma of neuropathic patients. Preliminary results of an attempt to identify the neurotoxin indicate that it is an acid-polyol derivative.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001001:Anura; D001681:Biological Assay; D006801:Humans; D009498:Neurotoxins / Q000097:blood / Q000302:isolation & purification* / Q000494:pharmacology; D011115:Polyneuropathies / Q000209:etiology; D013497:Sural Nerve / Q000187:drug effects; D014118:Toxins, Biological / Q000097:blood*; D014511:Uremia / Q000097:blood* / Q000150:complications
D009498:Neurotoxins; D014118:Toxins, Biological