Serum α2-macroglobulin in haemodialysis patients: Baseline and kinetic studies

A. Argilés, G. Mourad, C. M. Mion, P. G. Kerr, R. C. Atkins, A. Argilés

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Abstract

The pathogenesis of dialysis related amyloidosis remains unresolved despite the identification of β2-microglobulin (β2M) as the major protein constituent, as well as other proteins being present in the deposits. Among the latter we have assessed the serum concentrations of α2-macroglobulin (α2M) both in the baseline stage and during the haemodialysis (HD) procedure. We have also assessed the influence of the membrane on α2M kinetics. Fifteen HD patients with histologically proven dialysis-related amyloidosis (DRA group) and 15 HD patients clinically and radiologically considered dialysis-related amyloidosis free (control group) were included in the baseline study. Blood was sampled the day before the second dialysis of the week and α2M, β2M and α1, antitrypsin were determined along with the routine biological analysis of these patients. Serum α2M was greater in dialysis-related amyloidosis than in control patients (t = 2.35; P<0.026). Serum β2M was similar in both groups. The serum α2M and β2M correlated in patients with dialysis-related amyloidosis (r = 0.64; P<0.01), while no correlation was found in controls (r = 0.17; NS). Stepwise analysis taking the presence of dialysis-related amyloidosis as the dependent variable retained the serum α2M concentration as the first variable in the model (F = 4.4; partial r = 0.38; P<0.046). The same proteins were determined in another group of seven patients, before and hourly during HD as well as 2 and 8 h after the end of HD during nine consecutive dialyses (3 cycles of 3 HD each using AN69 and cuprophane membranes in a crossover design). Serum α2M significantly increased from hour 3 and continued to increase 2 hours post-HD (+11% and +9% with AN69 and cuprophane respectively; P<0.001). Total proteins peaked at hour 4 (+4% and +3% P<0.01) and decreased after HD. Serum β2M significantly decreased with AN69 HD (− 29% P<0.001) and remained unchanged during cuprophane HD. In conclusion, significant increases in serum α2M are observed immediately after and during the early post-dialysis periods, regardless of the membrane used. Further, serum α2M correlates with β2M only in patients with dialysis-related amyloidosis, and this variable was retained in the multivariate regression analysis to predict dialysis-related amyloidosis. Although the baseline results require confirmation with larger studies, we postulate that the present results are of relevance for dialysis-related amyloidosis pathogenesis since α2M, previously identified in dialysis related amyloid deposits, is closely related to acute-phase reactant proteins, and interacts with the main infiltrating cells of the deposits (macrophages). α2M modifications could represent a new manifestation of the inflammatory response to the haemodialysis procedure.

Original languageEnglish
Pages (from-to)1118-1123
Number of pages6
JournalNephrology Dialysis Transplantation
Volume8
Issue number10
DOIs
Publication statusPublished - 1 Jan 1993

Keywords

  • Dialysis-related amyloidosis
  • Haemodialysis
  • α macroglobulin
  • β macroglobulin

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