Amyloidosis, Beta2M (Dialysis-Related)
- Author: Anita Basu, MD; Chief Editor: Vecihi Batuman, MD, FACP, FASN more...
Background
Beta-2-microglobulin amyloidosis is a disabling condition that affects patients undergoing long-term hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD).[1, 2] Case reports involving patients with near end-stage renal disease also exist. It does not affect individuals with normal or mildly reduced renal function or patients with a functioning renal transplant.
Beta-2-microglobulin is a major constituent of amyloid fibrils.[3] Its accumulation has been shown to invade synovial membranes and osteoarticular sites, causing destructive osteoarthropathies, such as carpal tunnel syndrome, flexor tenosynovitis, subchondral bone cysts, and erosions, as well as pathologic fractures.
Visceral involvement has been found in different organs, such as the gastrointestinal tract, heart, and tongue, but overt manifestations are rare.
Pathophysiology
Beta-2-microglobulin is a glycosylated polypeptide with a molecular weight of 11,800 dalton. It comprises the beta chain of the human leukocyte antigen (HLA) class I molecule and has a prominent beta-pleated structure with characteristic amyloid fibrils. Beta-2-microglobulin is present on the surface of most nucleated cells and in most biologic fluids, including urine and synovial fluid. It circulates as an unbound monomer distributed in the extracellular space and polymerizes to form amyloid deposits in a variety of tissues. Two or three conformational isomers of beta(2)m are recognized in human serum by capillary electrophoresis.[4]
In the normally functioning kidney, beta-2-microglobulin is cleared by glomerular filtration and is catabolized in the proximal tubules. Reference range serum levels are 1.5-3 mg/L. In renal failure, impaired renal catabolism causes an increase in synthesis and a release of beta-2-microglobulin, and levels can increase 10- to 60-fold. Retention and accumulation of this type of amyloid protein is presumed to be the main pathogenic process underlying beta-2-microglobulin amyloidosis. There is also some suggestion that the dialysis process itself may stimulate beta-2-microglobulin synthesis by activation of complements and cytokine production. However, it is unlikely that this is a significant mechanism of dialysis-related amyloidosis (DRA) since the disease is also seen in patients on CAPD and people who have never been on dialysis.
Epidemiology
Frequency
United States
The incidence of DRA in the United States is not known; however, past studies have suggested an incidence of greater than 95% in patients on dialysis for more than 15 years.
Some European studies have suggested that DRA can be seen in as many as 20% of patients after 2-4 years of HD and in 100% after 13 years of HD. However, again, the overall incidence and prevalence of beta-2-microglobulin amyloidosis are not clear.
Most studies have focused on HD-associated amyloidosis and have been done before high-flux dialyzer use became commonplace.
There is some mention in the literature that the incidence and the prevalence in CAPD are less than in HD (because of residual renal function), while other European studies suggest that there is no significant difference in both the incidence and the prevalence.
Beta-2-microglobulin amyloidosis evolves predictably over time and is rare in the first few years of HD.
International
Studies in Japan suggest that most patients with carpal tunnel syndrome associated with beta-2-microglobulin amyloid deposits have undergone HD for 10 years or more. In one study, up to 50% of patients developed this complication after 20 years, and the percentage was even higher after 25 years.
Mortality/Morbidity
Patients receiving long-term dialysis can experience disabling musculoskeletal complications.[5] For individuals who are able to undergo renal transplantation, progression of the disease can be halted, but regression is unlikely. Rarely, submucosal bowel deposits have resulted in massive GI bleeding. Case reports of severe pulmonary hypertension and heart failure due to beta-2-microglobulin amyloid deposits in the interstitium and/or vasculature of the cardiovascular system also exist.
Race
No data comparing the incidence of disease in different groups exist.
Sex
The sex of the individual does not seem to influence risk.
Age
The incidence correlates with the increased age of the individual and the time on dialysis.
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