Is β2-microglobulin-related amyloidosis of hemodialysis patients a multifactorial disease? A new pathogenetic approach

Purpose: β2-microglobulin amyloidosis (Aβ 2 M) is one of the main long-term complications of dialysis treatment. The incidence and the onset of Aβ 2 M has been related to membrane composition and/or dialysis technique, with non-homogeneous results. This study was carried out to detect: i) the incidence of bone cysts and CTS from Aβ 2 M; ii) the difference in Aβ 2 M onset between cellulosic and synthetic membranes; iii) other risk factors besides the membrane. Methods: 480 HD patients were selected between 1986 to 2005 and grouped according to the 4 types of membranes used (cellulose, synthetically modified cellulose, synthetic low-flux, synthetic high-flux). The patients were analyzed before and after 1995, when the reverse osmosis treatment for dialysis water was started at our center, and the incidence of Aβ 2 M was compared between the two periods. Routine plain radiography, computer tomography (CT) and nuclear magnetic resonance imaging (MRI) as well as electromyography were used to investigate the clinical symptoms. Results: Bone cysts occurred in 29.2% of patients before 1995 vs. 12.2% after 1995 (p<0.0001). CTS occurred in 24% of patients before 1995 vs. 7.1% after 1995 (p<0.0001). Bone cysts and CTS occurred in older patients, who began dialysis at a late age, with high CRP, low albumin, low residual GFR, and low Hb. Cox regression analysis showed that the risk factor for bone cysts was high CRP (RR 1.3, p<0.01), while albumin (RR 0.14, p<0.0001) and residual GFR (RR 0.81, p<0.0001) were revealed to be protective factors. Cox analysis for CTS confirmed CRP as a risk factor (RR 1.2, p<0.01),and albumin (RR 0.59, p<0.0001) and residual GFR (RR 0.75, p<0.0001) as protective factors. The comparison obtained between membranes did not suggest any protective effect on Aβ 2 M. Conclusions: The findings that the inflammatory status as well as low albumin and the residual GFR of the uremic patient are predictive of Aβ 2 M lesions suggests that Aβ 2 M has a multifactorial origin rather than being solely a membrane- or technique-related side effect.