Uremic Neurotoxin in the Middle Molecular Weight Range

Abstract

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.

The Progression of Uremic Polyneuropathy in Patients on Hemodialysis and Hemofiltration: A Two‐Year Study

“…Also Bozek et al [14] suggested that hemofiltration should be applied in patients who have complications owing to the accumulation of substances of middle molecular weight, as this method has proved to be efficient in the elimination of such substances. Moreover, Man et al [15] have studied the fraction b4–2 and found that serum levels in healthy persons were 1 mg/L, which was increased to 4.6 ± 0.2 mg/L in uremic patients. The highest levels (13 – 19 mg/L) were observed in uremic patients with polyneuropathy.…”

“…The highest levels (13 – 19 mg/L) were observed in uremic patients with polyneuropathy. Furthermore, in experimental models, the group proved that the fraction b4–2 exhibits neurotoxic effects at high levels comparable to those found in the serum of uremic patients with polyneuropathy [15].…”

Perfusion of Uremic Blood Ultrafiltrate on Uncoated Charcoal

“…Jaffrin MY, Gupta A previous investigation has shown by chromatographic data (1) that dialysis is unable to remove a large amount of compounds that are accumulated in the body during chronic renal failure. It is widely accepted that only these accumulants are responsi-ble for the unphysiology and complications in dialysed patients (2)(3)(4)(5)(6).…”