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Published on: November 10, 2021
A circulating beta 2-microglobulin intermediate in hemodialysis patients.
Yoshinori Uji1, Yoshihiro Motomiya, Yukio Ando
1Clinical Center, Toyama University Hospital, Toyama, Japan.
Dialysis-related amyloidosis involves misfolded beta(2)-microglobulin (beta(2)m). This study found intermediate beta(2)-microglobulin (I-beta(2)m) is poorly removed during dialysis, unlike native beta(2)-microglobulin (N-beta(2)m).
Area of Science:
- Biochemistry
- Nephrology
- Analytical Chemistry
Background:
- Dialysis-related amyloidosis is linked to misfolded beta(2)-microglobulin (beta(2)m).
- Conformational variants of beta(2)m have not been previously reported in clinical settings.
- Capillary electrophoresis is a method for identifying beta(2)m conformational variants.
Purpose of the Study:
- To measure native beta(2)-microglobulin (N-beta(2)m) and intermediate beta(2)-microglobulin (I-beta(2)m) in serum.
- To assess the removal of N-beta(2)m and I-beta(2)m during hemodialysis (HD) and online hemodiafiltration (HDF).
- To investigate the presence of beta(2)m conformational isomers in human serum.
Main Methods:
- Capillary electrophoresis was employed to quantify N-beta(2)m and I-beta(2)m.
- Serum samples were analyzed from 31 HD patients (pre- and post-dialysis), 5 chronic renal failure (CRF) patients, and 5 healthy individuals.
- The study compared two dialysis methods: HD with polymethylmethacrylate (PMMA) membranes and HDF with polysulfone (PS) membranes.
Main Results:
- Predialysis serum levels were 2.7 +/- 1.4 mg/l for I-beta(2)m and 29.4 +/- 6.8 mg/l for N-beta(2)m in HD patients.
- Serum N-beta(2)m significantly decreased during both HD (32.8%) and HDF (71.2%).
- Serum I-beta(2)m removal varied widely (-36.4% to +203.5% with PMMA, -70.8% to +62.5% with PS), indicating poor and inconsistent removal.
Conclusions:
- Two to three beta(2)m conformational isomers are likely present in all human serum.
- Despite no progressive increase, I-beta(2)m exhibits significantly poorer removal compared to N-beta(2)m during dialysis, including HDF.
- The observed rebound profile suggests I-beta(2)m may become immobilized in the extracellular space.
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