Dialysis-related amyloidosis: challenges and solutions

Abstract

Amyloidosis refers to the extracellular tissue deposition of fibrils composed of lowmolecular-weight subunits of a variety of proteins. These deposits may result in a wide range of clinical manifestations depending upon their type, location, and the amount of deposition. Dialysis-related amyloidosis is a serious complication of long-term dialysis therapy and is characterized by the deposition of amyloid fibrils, principally composed of b2 microglobulins (b2M), in the osteoarticular structures and viscera. Most of the b2M is eliminated through glomerular filtration and subsequent reabsorption and catabolism by the proximal tubules. As a consequence, the serum levels of b2M are inversely related to the glomerular filtration rate; therefore, in end-stage renal disease patients, b2M levels increase up to 60-fold. Serum levels of b2M are also elevated in several pathological conditions such as chronic inflammation, liver disease, and above all, in renal dysfunction. Retention of amyloidogenic protein has been attributed to several factors including type of dialysis membrane, prolonged uremic state and/or decreased diuresis, advanced glycation end products, elevated levels of cytokines and dialysate. Dialysis treatment per se has been considered to be an inflammatory stimulus, inducing cytokine production (such as interleukin-1, tumor necrosis factor-α, interleukin-6) and complement activation. The released cytokines are thought to stimulate the synthesis and release of b2M by the macrophages and/or augment the expression of human leukocyte antigens (class I), increasing b2M expression. Residual renal function is probably the best determinant of b2M levels. Therefore, it has to be maintained as long as possible. In this article, we will focus our attention on the etiology of dialysis-related amyloidosis, its prevention, therapy, and future solutions.

Hemodialysis‐associated soft tissue amyloidomas of the chest and abdominal wall

“…In the past when older, lowerflux dialysis membranes such as cellulose diacetate were used, dialysis clearance of middle-molecules such as β 2microglobulin was significantly impaired. 18,19 Of note, his pre-dialysis serum β 2 M level while on a high-flux dialyzer was lower than that typically found in the hemodialysis population. 16,17 Overall, more advanced HD technologies including highflux dialyzers, biocompatible membranes, ultra-pure dialysate, and high-tech RO plants have reduced the likelihood of DRA.…”

“…11 DRA has been seen less frequently since the advent of advanced HD technologies. 12,18 Although our patient had been using a highflux dialyzer recently, his early renal failure and prolonged duration of dialysis certainly placed him at higher risk for DRA. 15,16 Nowadays, the removal of β 2 M has improved with newer, higher-flux dialyzers such as cellulose triacetate (a modified cellulosic membrane) and polysulfone (a synthetic polymer).…”

“…16,17 Overall, more advanced HD technologies including highflux dialyzers, biocompatible membranes, ultra-pure dialysate, and high-tech RO plants have reduced the likelihood of DRA. 12,18 Although our patient had been using a highflux dialyzer recently, his early renal failure and prolonged duration of dialysis certainly placed him at higher risk for DRA. 18,19 Of note, his pre-dialysis serum β 2 M level while on a high-flux dialyzer was lower than that typically found in the hemodialysis population.…”

Clinical and hematological data to group different chronic kidney disease patients: A practical approach to establish different groups of patients

“…During hemodialysis, contact between antigen presenting cells (APCs) and the dialyzer membrane occur, causing mechanical stress and APCs activation . There is also exposure to other factors, such as oxidized lipoproteins (oxidized LDL), bacterial degradation products (eg, LPS), or nonenzymatic glycosylation of proteins, which may contribute to immune system activation…”

“…[8][9][10] During hemodialysis, contact between antigen presenting cells (APCs) and the dialyzer membrane occur, causing mechanical stress and APCs activation. 5,11,12 There is also exposure to other factors, such as oxidized lipoproteins (oxidized LDL), bacterial degradation products (eg, LPS), or nonenzymatic glycosylation of proteins, which may contribute to immune system activation. 11 Chronic activation of APCs induces strong CD4 T-cell activation and differentiation 7,13 ; however, over a long period, this chronic activation could lead to a reduction in the peripheral CD4 T lymphocyte counts.…”