The unresolved problem of beta-2 microglobulin amyloid deposits in the intervertebral discs of long-term dialysis patients

Abstract

Background: Dialysis-related destructive spondyloarthropathy caused by beta-2 microglobulin (β2M) amyloid deposits in intervertebral discs is a major burden for patients undergoing long-term dialysis. This study aimed to quantify the presence of β2M amyloid deposits in the intervertebral disc tissue of such patients and analyze whether there was a significant correlation between β2M accumulation and the duration of dialysis.

Methods: Two groups of patients who had undergone surgery for degenerative spinal pathologies were selected: the dialysis group (n = 29) with long-term dialysis and the control group (n = 10) with no renal impairment. Tissue sections were prepared from specimens of intervertebral disc tissue obtained during spinal surgery and analyzed via histological staining, including immunohistochemistry (IHC) and Congo red.

Results: There was a statistically significant multifold increase of β2M expression in the disc tissue of long-term dialysis patients when compared to non-dialysis patients, as shown by both IHC (0.019 ± 0.023 μm² vs. 0.00020 ± 0.00033 μm², respectively; p = 0.012) and Congo red staining (0.027 ± 0.041 μm² vs. 9.240 × 10^-5 ± 5.261 × 10^-5 μm², respectively; p = 0.047). We also note a moderate strength positive correlation between the duration of dialysis and positive IHC (r = 0.39; p = 0.015) and Congo-red staining (r = 0.42; p = 0.007).

Conclusions: The problem of β2M amyloidosis in long-term dialysis patients remains unresolved even with predominant use of high-flux dialysis membranes. This highlights the insufficiency of current dialysis modalities to effectively filter β2M.

Keywords: Amyloid; Beta-2 microglobulin; Congo red; Dialysis; Intervertebral disc; Spondyloarthropathy.

Fig. 1

Representative histological images of intervertebral disc sections from non-dialysis (0) and dialysis patients (1–3). a Congo red staining under normal light and amyloid deposition indicated in dark red. b Congo red staining under polarized light and amyloid deposition indicated in apple green. c IHC staining and β2M expression indicated in dark brown. Magnification: ×40

Fig. 2

Western blot analysis of the intervertebral disc tissues of one non-dialysis and one dialysis patient. a Western blot analysis of β2M using beta-actin as a loading control. b Sagittal cut MRI image from the non-dialysis patient showed the right L5/S1 herniated nucleus pulposus with grade III degeneration. c Sagittal cut MRI image from the dialysis patient showed left L5/S1 extrusion type herniated nucleus pulposus with Grade IV degeneration