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

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.