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

Abstract

BackgroundDialysis-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.MethodsTwo 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.ResultsThere 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).ConclusionsThe 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.

An Organ System–Based Approach to Differential Diagnosis of Amyloid Type in Surgical Pathology

“…15 In patients receiving dialysis for more than 10 years, Ab2M displays osteoarticular tropism, presenting primarily as carpal tunnel syndrome but also with symptoms related to shoulder, hip, intervertebral disc, paravertebral ligament, and subchondral bone amyloid deposition. [73][74][75] The incidence of joint involvement in patients with AL amyloidosis has been reported between 0.2% and 5%, with a male predilection. 73 Age-related ATTR is increasingly recognized as a cause of carpal tunnel syndrome and can precede cardiac manifestations.…”

<p>Measuring serum beta2-microglobulin to predict long-term mortality in hemodialysis patients using low-flux dialyzer reuse</p>

“…DRA is a serious complication of long-term dialysis therapy and is characterized by the deposition of amyloid fibrils, principally composed of β2-M, in the osteoarticular structures and viscera. The duration on hemodialysis treatment plays an important role in the development of DRA 24–26. Carpal tunnel syndrome and pain of shoulder are two of the clinical manifestations of the DRA.…”

Beta-2 Microglobulin Amyloidosis: Past, Present, and Future

“…First described in 1984 in long-term HD patients, DSA more commonly affects the more mobile C5-C7 and L3-L5 vertebrae 54 . Amyloid has also been verified in lesions surrounding the spine including the ligamentum flavum, zygapophysial (facet) joints, and intervertebral disks 55 . DSA can produce difficulty in ambulation and loss of muscle mass.…”