Circulating level of alpha(2)-macroglobulin-beta(2)-microglobulin complex in hemodialysis patients

Background. The presence of a alpha(2)-macroglobulin (alpha(2)M) in amyloid tissue from patients with dialysis-related amyloidosis (DRA) was demonstrated by Argiles et al in 1989. Thereafter, the formation of the complex of beta(2)-microglobulin (beta(2)m) with alpha(2)m was confirmed directly by in vitro study. In Alzheimer's disease, complex formation of amyloid beta-peptide and a alpha(2)M is considered to play an important role in the pathogenesis by modifying the degradation processes of amyloid protein. Thus, we hypothesized that the a alpha(2)M-beta(2)m complex is an important factor in the pathogenesis of DRA as well. Here, we measured the circulating levels of a alpha(2)M-beta(2)m complex in the maintenance hemodialysis patients and discussed about its clinical significance in DRA. Methods. One hundred and thirty-seven hemodialysis patients and 11 prehemodialysis chronic renal failure (CRF) patients were included in this study. The affinity of purified a alpha(2)M for beta(2)m was confirmed by a highly sensitive 27 MHz quartz crystal microbalance (QCM). The presence of circulating a alpha(2)M-beta(2)m complex was analyzed by immunoblotting analysis. Furthermore, the serum levels of a alpha(2)M-beta(2)m complex were measured by sandwich enzyme immunoassay. Results. QCM analysis revealed the high affinity of alpha(2)M for beta(2)m. The presence of circulating alpha(2)M-beta(2)m complex was detected in two out of a total 11 prehemodialysis CRF patients and in 95 out of the total of 137 hemodialysis patients. None of the healthy subjects, however, were observed to present with any alpha(2)M-beta(2)m complex. Serum levels of the alpha(2)M-beta(2)m complex were correlated to the duration of hemodialysis (P = 0.043). Serum levels of the alpha(2)M-beta(2)m complex were significantly higher in patients with high DRA score than in patients with negative DRAscore (P = 0.018). Moreover, serum levels of the alpha(2)M-beta(2)m complex showed significantly lower in the hemodiafiltration patients compared to the hemodialysis patients (P = 0.002) and showed a strong correlation with DRA score in hemodialysis patients excluding 11 hemodiafiltration patients (P = 0.0004). Conclusion. This study is the first to demonstrate the presence of circulating alpha(2)M-beta(2)m complex in hemodialysis patients. Furthermore, we observed the correlation between serum levels of alpha(2)M-beta(2)m complex and clinical characteristics of DRA. Thus we concluded that a formation of an alpha(2)M-beta(2)m complex may be implicated in DRA.