Histological prevalence of β2-microglobulin amyloidosis in hemodialysis: A prospective post-mortem study

Jadoul, Michel; Garbar, Christian; Noël, H.; Sennesael, Jacques; Vanholder, Raymond; Bernaert, P.; Rorive, Georges; Hanique, G.; Strihou, Charles van Ypersele de

doi:10.1038/ki.1997.262

Cited by 153 publications

(93 citation statements)

References 14 publications

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“…However, a postmortem study showed that b 2 M amyloid deposition occurs in 21% of cases within 2 years and in 33% within 4 years after initiation of HD. 24 Although the significance of pathologically evident but Abbreviations: CaÂP, calcium-phosphorus product; HD, hemodialysis; HDL-C, high-density lipoprotein cholesterol; hs-CRP, high-sensitivity C-reactive protein; IMT, intima-media thickness; iPTH, intact parathyroid hormone; LDL-C, low-density lipoprotein cholesterol. clinically silent amyloid deposition is unclear, it is notable that in patients on HD, pathological distribution of b 2 M amyloid deposition was consistent with that of tissue calcification in previous reports.…”

Section: Discussionmentioning

confidence: 99%

Differences in associated factors between aortic and mitral valve calcification in hemodialysis

et al. 2010

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Increased prevalence of aortic and mitral valve calcification has been reported in patients on hemodialysis, but it remains unknown whether aortic and mitral valve calcification arise from similar pathogenesis. We detected heart valve calcification using two-dimensional echocardiography, and we related valve calcification to various clinical parameters in patients treated with hemodialysis three times a week for more than 1 year. In 112 patients (77 men and 35 women, age 67±10 years, duration on hemodialysis 95 ± 67 months), aortic and mitral valve calcification were observed in 84 (75.0%) and 58 (51.7%) patients, respectively. Aortic valve calcification was associated with increased age, higher serum calcium, lower serum albumin, lower total cholesterol and higher high-sensitivity C-reactive protein. Multivariate analysis showed that increased age and higher serum calcium were independently associated with aortic valve calcification. Conversely, mitral valve calcification was associated with increased age, higher high-sensitivity C-reactive protein and higher serum b 2 -microglobulin, but not with higher serum calcium. In multivariate analysis, increased age and higher serum b 2 -microglobulin were independently associated with mitral valve calcification. Serum b 2 -microglobulin was associated with longer duration on hemodialysis, malnutrition inflammation (lower serum albumin and higher high-sensitivity C-reactive protein) and dyslipidemia. Considering the results in previous studies showing that the distribution of b 2 -microglobulin amyloid deposition was consistent with that of tissue calcification in patients on hemodialysis, b 2 -microglobulin may have pathogenic roles in valve calcification.

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Section: Discussionmentioning

confidence: 99%

Differences in associated factors between aortic and mitral valve calcification in hemodialysis

et al. 2010

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“…21 A large-scale postmortem study showed amyloid deposition in sternoclavicular joint and in the knee in 21%, 33%, 50%, 90%, and 100% of patients receiving HD for <2 years, after 2-4 years, 4-7 years, 7-13 years, and >13 years, respectively. 2 As regards PD, there are little data about the rate of DRA because the dialysis vintage of patients on PD is usually not so prolonged as in HD and there are only a few studies comparing the prevalence of DRA in HD and PD. Accumulation of amyloid may occur more slowly in patients treated by CAPD because serum b2M levels are lower in patients treated by CAPD in comparison to patients on HD with low-flux membranes.…”

Section: Epidemiology and Risk Factorsmentioning

confidence: 99%

“…2 The ameliorations in dialysis techniques grow survival rates of hemodialyzed patients and, as a consequence, the risk of DRA. 25 • Age of onset of HD treatment: It is considered as an independent risk factor.…”

Section: Epidemiology and Risk Factorsmentioning

confidence: 99%

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Dialysis-related amyloidosis: challenges and solutions

Scarpioni¹,

Ricardi²,

Albertazzi³

et al. 2016

IJNRD

113

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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.

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“…Different proteins and polypeptides can acquire the abnormal conformational changes that lead to amyloid formation, and at least 19 different proteins are now known to be involved in the generation of amyloid in vivo (1). In the case of dialysis-related amyloidosis the protein involved is ␤ 2 -microglobulin (␤ 2 m), 1 which aggregates as amyloid fibrils in joints and tissues in ϳ20% of patients with kidney failure within 2 years after the onset of hemodialysis treatment (2). This type of amyloidosis does not seem to require a mutated, processed, or chemically modified precursor protein.…”

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confidence: 99%

Conformational Intermediate of the Amyloidogenic Protein β2-Microglobulin at Neutral pH

Heegaard¹,

Sen²,

Kaarsholm³

et al. 2001

Journal of Biological Chemistry

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Aggregation and fibrillation of ␤ 2 -microglobulin are hallmarks of dialysis-related amyloidosis. We characterize perturbations of the native conformation of ␤ 2 -microglobulin that may precede fibril formation. For a ␤ 2 -microglobulin variant cleaved at lysine 58, we show using capillary electrophoresis that two conformers spontaneously exist in aqueous buffers at neutral pH. Upon treatment of wild-type ␤ 2 -microglobulin with acetonitrile or trifluoroethanol, two conformations were also observed. These conformations were in equilibrium dependent on the sample temperature and the percentage of organic solvent present. Circular dichroism showed a loss of ␤-structures and gain of ␣-helices. Reversal to the native conformation occurred when removing the organics. Affinity capillary electrophoresis experiments showed increased specific interactions of the nonnative ␤ 2 -microglobulin conformation with the dyes 8-anilino-1-naphthalene sulfonic acid and Congo red. The observations may relate to early folding events prior to amyloid fibrillation and facilitate the development of methods to detect and inhibit pro-amyloid protein and peptide conformations.Abnormal protein folding leads to amyloid deposition in a number of different chronic disorders including Alzheimer's disease, senile systemic amyloidosis, transmissible spongiform encephalopathies, and dialysis-related amyloidosis (1). Different proteins and polypeptides can acquire the abnormal conformational changes that lead to amyloid formation, and at least 19 different proteins are now known to be involved in the generation of amyloid in vivo (1). In the case of dialysis-related amyloidosis the protein involved is ␤ 2 -microglobulin (␤ 2 m), 1 which aggregates as amyloid fibrils in joints and tissues in ϳ20% of patients with kidney failure within 2 years after the onset of hemodialysis treatment (2). This type of amyloidosis does not seem to require a mutated, processed, or chemically modified precursor protein. Although the cause of the abnormal folding in vivo is unknown, it has been reported recently that ␤ 2 m can be induced to generate amyloid fibrils in vitro at low pH and high salt conditions (3) and that fibrillar ␤ 2 m can be refolded back in vitro (4).Similar pre-amyloid folding states have now been demonstrated for a number of amyloidosis-related proteins (5-9) and also in other proteins and peptides without known amyloid disease associations (10 -13). ␤ 2 m is an attractive protein for studying amyloid-promoting folding events because it is small (M r ϭ 11,729), nonglycosylated, nonpolymorphic, and has a simple native structure (14), i.e. it is a one-chain all ␤-protein with two antiparallel pleated sheets of ␤-strands linked together by a disulfide bridge (15). It is structurally homologous to constant domains of immunoglobulins (14). In chronic renal failure ␤ 2 m serum concentrations may increase 10 -70 times despite dialysis, but there is no simple relationship between ␤ 2 m serum concentrations and the extent of amyloidosis (16 The Lys 58 -␤ 2 ...

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Histological prevalence of β2-microglobulin amyloidosis in hemodialysis: A prospective post-mortem study

Cited by 153 publications

References 14 publications

Differences in associated factors between aortic and mitral valve calcification in hemodialysis

Differences in associated factors between aortic and mitral valve calcification in hemodialysis

Dialysis-related amyloidosis: challenges and solutions

Conformational Intermediate of the Amyloidogenic Protein β2-Microglobulin at Neutral pH

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