PROGRESS IN UREMIC TOXIN RESEARCH: Beta2‐Microglobulin

Drüeke, Tilman B.; Massy, Ziad A.

doi:10.1111/j.1525-139x.2009.00584.x

Cited by 108 publications

(88 citation statements)

References 25 publications

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“…Dialysis Related Amyloidosis (DRA) is a pathological state afflicting patients suffering from kidney failure treated by long-term hemodialysis, related to inefficient b2m catabolism. 2,3 Under such pathological conditions the concentration of circulating b2m increases by a factor of 10-50, 2,4 leading to b2m…”

Section: Introductionmentioning

confidence: 99%

DE‐loop mutations affect β2 microglobulin stability, oligomerization, and the low‐pH unfolded form

et al. 2010

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b2 microglobulin (b2m) is the light chain of class-I major histocompatibility complex (MHC-I). Its accumulation in the blood of patients affected by kidney failure leads to amyloid deposition around skeletal joints and bones, a severe condition known as Dialysis Related Amyloidosis (DRA). In an effort to dissect the structural determinants of b2m aggregation, several b2m mutants have been previously studied. Among these, three single-residue mutations in the loop connecting strands D and E (W60G, W60V, D59P) have been shown to affect b2m amyloidogenic properties, and are here considered. To investigate the biochemical and biophysical properties of wild-type (w.t.) b2m and the three mutants, we explored thermal unfolding by Trp fluorescence and circular dichroism (CD). The W60G mutant reveals a pronounced increase in conformational stability. Protein oligomerization and reduction kinetics were investigated by electrospray-ionization mass spectrometry (ESI-MS). All the mutations analyzed here reduce the protein propensity to form soluble oligomers, suggesting a role for the DE-loop in intermolecular interactions. A partially folded intermediate, which may be involved in protein aggregation induced by acids, accumulates for all the tested proteins at pH 2.5 under oxidizing conditions. Moreover, the kinetics of disulfide reduction reveals specific differences among the tested mutants. Thus, b2m DE-loop mutations display long-range effects, affecting stability and structural properties of the native protein and its low-pH intermediate. The evidence presented here hints to a crucial role played by the DE-loop in determining the overall properties of native and partially folded b2m.

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Section: Introductionmentioning

confidence: 99%

DE‐loop mutations affect β2 microglobulin stability, oligomerization, and the low‐pH unfolded form

et al. 2010

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“…The accumulation of polymerized β 2 -microglobulin during the years of dialysis therapy leads to severe bone and soft tissue damage. 14,15 Two different dialysis modalities for solute transport across artificial kidney membranes are possible: diffusion and convection. Diffusive-based HD modality provides good removal of small molecules, but removal of middleand large-size uremic toxins is limited even when highflux membranes are used.…”

Section: Introductionmentioning

confidence: 99%

Influence of Dialysis Modality and Membrane Flux on Quality of Life in Hemodialysis Patients

Knežević¹,

Djordjević²,

Radovanovic-Velickovic³

et al. 2012

Renal Failure

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Background: The quality of life in patients undergoing hemodialysis is significantly disturbed. There are data that hemodiafiltration (HDF) may be more effective than conventional hemodialysis in the removal of uremic toxins and may reduce frequency and severity of intradialytic and postdialysis adverse symptoms in patients. Also, some researchers suggest advantages of using high-flux membranes compared with low-flux. Objective: The aim of this study was to examine whether hemodialysis modality and membrane flux, independent of membrane biocompatibility, make differences in quality of life in patients. Methods: In our cross-sectional study, we evaluated 124 patients who were divided, based on therapy, into three groups: online HDF, high-flux hemodialysis, and low-flux hemodialysis. Data were collected using the Short Form-36 questionnaire combined with special questionnaire, which included demographic and clinically related questions. Results: Health-related quality of life was better in patients on HDF compared with patients on hemodialysis, especially compared with low-flux hemodialysis patients in most of the scales and in both dimensions: physical component scale and mental component scale. There were no statistically significant differences in Short Form-36 domains between high-flux hemodialysis and low-flux hemodialysis. Conclusion: Our data suggest the potential advantages of HDF with regard to influence on quality of life, which is sufficient to justify further research in prospective and longitudinal study design.

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“…Serum b2-microglobulin seems to be an inconstant indicator of dialy-166 Bellini, Paparella: Dialysis arthropathy and the biochemical database sis-related arthropathy. In our study, this common arthropathy dialysis-related indicator, b2-microglobulin (15,16), was si milar in the two groups.…”

Section: Discussionmentioning

confidence: 83%

Clinical Biochemistry Database Analysis: A Restricted Dialysis Cohort /

Bellini¹,

Paparella²

2013

Journal of Medical Biochemistry

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SummaryBackground: A retrospective study was undertaken to investigate the biochemistry data of a restricted cohort of dialysisrelated arthropathy patients. The aim of our study was to characterize this specific cohort of dialysis patients using a clinical chemistry database analysis. Methods: An elaboration of more than 160,000 items of biochemical data, collected from 2001 to 2011, was made of 50 patients, 25 with dialysis-related arthropathy and 25 patients asymptomatic for arthropathy. A Student's t-test was applied, considering a P-value less than 0.05 as statistically significant. Results: Significant and relevant unexpected biochemical differences were found between the two groups of patients. The serum level of b2-microglobulin was similar, while ferritin values were significantly higher in symptomatic patients. We excluded the possibility that the ferritin difference between the two groups was due to different iron storage and to an inflammatory profile. Conclusions: The correct use of a biochemical database could permit to identify significant values which must be correlated with clinical data, but which could be the first step to a wider research.

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PROGRESS IN UREMIC TOXIN RESEARCH: Beta2‐Microglobulin

Cited by 108 publications

References 25 publications

DE‐loop mutations affect β2 microglobulin stability, oligomerization, and the low‐pH unfolded form

DE‐loop mutations affect β2 microglobulin stability, oligomerization, and the low‐pH unfolded form

Influence of Dialysis Modality and Membrane Flux on Quality of Life in Hemodialysis Patients

Clinical Biochemistry Database Analysis: A Restricted Dialysis Cohort /

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