Is beta2-microglobulin-related amyloidosis of hemodialysis patients a multifactorial disease? A new pathogenetic approach

Purpose: β2-microglobulin amyloidosis (Aβ2M) is one of the main long-term complications of dialysis treatment. The incidence and the onset of Aβ2M 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 Aβ2M; ii) the difference in Aβ 2M 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 Aβ2M 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 Aβ2M. Conclusions: The findings that the inflammatory status as well as low albumin and the residual GFR of the uremic patient are predictive of Aβ2M lesions suggests that Aβ2M has a multifactorial origin rather than being solely a membrane- or technique-related side effect.