The pathogenesis of dialysis related amyloidosis remains unresolveddespite the identification of ß
2-microglobulin (ß
2M)as the major protein constituent, as well as other proteinsbeing present in the deposits. Among the latter we have assessedthe serum concentrations of
2-macroglobulin (
2M) both in thebaseline stage and during the haemodialysis (HD) procedure.We have also assessed the influence of the membrane on
2M kinetics. Fifteen HD patients with histologically proven dialysis-relatedamyloidosis (DRA group) and 15 HD patients clinically and radiologicallyconsidered dialysis-related amyloidosis free (control group)were included in the baseline study. Blood was sampled the daybefore the second dialysis of the week and
2M, ß
2Mand
1, antitrypsin were determined along with the routine biologicalanalysis of these patients. Serum
2M was greater in dialysis-relatedamyloidosis than in control patients (
t = 2.35;
P<0.026).Serum ß
2M was similar in both groups. The serum
2Mand ß
2M correlated in patients with dialysis-relatedamyloidosis (
r = 0.64;
P<0.01), while no correlation wasfound in controls (
r = 0.17; NS). Stepwise analysis taking thepresence of dialysis-related amyloidosis as the dependent variableretained the serum
2M concentration as the first variable inthe model (F = 4.4; partial
r = 0.38;
P<0.046). The sameproteins were determined in another group of seven patients,before and hourly during HD as well as 2 and 8 h after the endof HD during nine consecutive dialyses (3 cycles of 3 HD eachusing AN69 and cuprophane membranes in a crossover design).Serum
2M significantly increased from hour 3 and continued toincrease 2 hours post-HD (+11% and +9% with AN69 and cuprophanerespectively;
P<0.001). Total proteins peaked at hour 4 (+4% and +3%
P<0.01) and decreased after HD. Serum ß
2Msignificantly decreased with AN69 HD ( 29%
P<0.001)and remained unchanged during cuprophane HD. In conclusion, significant increases in serum
2M are observedimmediately after and during the early post-dialysis periods,regardless of the membrane used. Further, serum
2M correlateswith ß
2M only in patients with dialysis-related amyloidosis,and this variable was retained in the multivariate regressionanalysis to predict dialysis-related amyloidosis. Although thebaseline results require confirmation with larger studies, wepostulate that the present results are of relevance for dialysis-relatedamyloidosis pathogenesis since
2M, previously identified indialysis related amyloid deposits, is closely related to acute-phasereactant proteins, and interacts with the main infiltratingcells of the deposits (macrophages).
2M modifications couldrepresent a new manifestation of the inflammatory response tothe haemodialysis procedure.
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