Effect of albumin in patients receiving hemodialysis on β2-microglobulin amyloid fibril formation

Dialysis-related amyloidosis (DRA) involves β2-microglobulin (β2M) amyloid (Aβ2M) deposition. While albumin suppresses amyloidogenesis in vitro, the impact of its quality (oxidation/uremic toxin binding) in patients receiving hemodialysis (HD) remains unclear. We investigated how albumin quantity/quality in patients receiving HD affects Aβ2M fibrillogenesis. Serum from patients receiving HD (n = 30) and healthy individuals (n = 30) was incubated with β2M monomers. Fibrillogenesis was monitored via Thioflavin T (ThT) fluorescence. Oxidized albumin and uremic toxins were quantified using liquid chromatography-mass spectrometry. Serum suppressed Aβ2M amyloid fibril formation in a concentration-dependent manner. Compared to healthy serum, HD serum showed significantly higher maximum ThT fluorescence (23.3 ± 5.2 vs. 16.2 ± 8.4 a.u., p < 0.001) and shorter half times (37.2 ± 10.3 vs. 51.6 ± 13.7 h, p < 0.001). Serum albumin levels were correlated with ThTmax (r = −0.53, p < 0.001) and half time (r = 0.59, p < 0.001). In multiple regression analyses, albumin concentration was independently associated with both parameters, whereas oxidized albumin and uremic toxins were not significantly associated. HD serum showed a reduced suppressive effect on Aβ2M amyloid fibril formation. Albumin quantity, rather than quality, primarily determines Aβ2M amyloidogenesis.