Synthesis of ,β2-Microglobulin in Lymphocyte Culture: Role of Hemodialysis, Dialysis Membranes, Dialysis-Amyloidosis, and Lymphokines

Campistol, Josep M.; Molina, Rafael; Bernard, David B.; Rodriguez, R.; Mirapeix, E; Múñoz-Gómez, J; Revert, Li.

doi:10.1016/s0272-6386(12)80432-x

Cited by 14 publications

(7 citation statements)

References 25 publications

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“…Although suggested by some in vitro studies (324, 325), other ex vivo (326, 327) and in vivo (328) investigations did not demonstrate an effect of flux on β 2 M gene transcription or protein expression. On the other hand, both in vitro (329) and in vivo (328) flow cytometric studies have shown that dialysis with LF membranes is associated with a larger dissociation of β 2 M from the HLA-I complex compared to their HF-HD counterparts.…”

Section: β2m: Synthesis and The Way Forwardmentioning

confidence: 87%

Rediscovering Beta-2 Microglobulin As a Biomarker across the Spectrum of Kidney Diseases

et al. 2017

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There is currently an unmet need for better biomarkers across the spectrum of renal diseases. In this paper, we revisit the role of beta-2 microglobulin (β2M) as a biomarker in patients with chronic kidney disease and end-stage renal disease. Prior to reviewing the numerous clinical studies in the area, we describe the basic biology of β2M, focusing in particular on its role in maintaining the serum albumin levels and reclaiming the albumin in tubular fluid through the actions of the neonatal Fc receptor. Disorders of abnormal β2M function arise as a result of altered binding of β2M to its protein cofactors and the clinical manifestations are exemplified by rare human genetic conditions and mice knockouts. We highlight the utility of β2M as a predictor of renal function and clinical outcomes in recent large database studies against predictions made by recently developed whole body population kinetic models. Furthermore, we discuss recent animal data suggesting that contrary to textbook dogma urinary β2M may be a marker for glomerular rather than tubular pathology. We review the existing literature about β2M as a biomarker in patients receiving renal replacement therapy, with particular emphasis on large outcome trials. We note emerging proteomic data suggesting that β2M is a promising marker of chronic allograft nephropathy. Finally, we present data about the role of β2M as a biomarker in a number of non-renal diseases. The goal of this comprehensive review is to direct attention to the multifaceted role of β2M as a biomarker, and its exciting biology in order to propose the next steps required to bring this recently rediscovered biomarker into the twenty-first century.

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Section: β2m: Synthesis and The Way Forwardmentioning

confidence: 87%

Rediscovering Beta-2 Microglobulin As a Biomarker across the Spectrum of Kidney Diseases

et al. 2017

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“…In addition, lysosomal enzymes such as myeloperoxidase (MPO) and elastase, various cytokines, and active oxygen species are released [6]. These substances may enhance the development of complications due to dialysis, such as accelerated atherosclerosis, increased susceptibility to infection, malignant tumors, and amyloidosis [7, 8]. Although the transient neutropenia during a hemodialysis (HD) session is a well-known phenomenon and has been attributed to the cellulose dialysis membrane [9, 10], there is so far no appropriate membrane material to study this phenomenon.…”

Section: Introductionmentioning

confidence: 99%

Reduction of Neutrophil Activation by Vitamin E Modified Dialyzer Membranes

Omata¹,

Higuchi²,

Demura

et al. 2000

Nephron

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Background/Aim: Transient leukopenia during hemodialysis due to neutrophil activation is attributed to bioincompatibility of the dailysis membrane, but the mechanism remains unclear. We studied the mechanism of neutrophilic activation by comparing a vitamin E modified membrane (CLEE) and a regular cellulose membrane (CLSS). Methods: (1) CLSS and CLEE membranes were used in a crossover clinical study in 7 chronic hemodialysis patients. Neutropenia, CD11b expression, and plasma C3a and myeloperoxidase concentrations were compared between the two dialyzer membranes. (2) Normal blood was circulated through CLEE and CLSS minimodels, and the same parameters were compared. (3) Blood samples with modified complement activities (EDTA: both classical and alternative pathways inactivated; EGTA+Mg: classical pathway inactivated; heating: alternative pathway inactivated; control: no modification) were incubated in the CLSS minimodel, and the neutrophilic activation was compared. Results: In clinical hemodialysis, neutropenia, CD11b expression, and C3a and myeloperoxidase levels were significantly lower when CLEE membranes were used. The same tendency was observed in minimodels. However, the degrees of inhibition in clinical dialysis, especially at the venous line, were significantly higher than in minimodels. As compared with controls, CD11b expression and myeloperoxidase level were significantly lower when both classical and alternative pathways were inactivated or when the classical pathway alone was inactivated, but were not significantly different when the alternative pathway alone was inactivated. Conclusions: Vitamin E modification of the dialyzer reduces some reactions of neutrophilic activation, such as CD11b expression and myeloperoxidase release, more effectively in the clinical situation than in ex vivo models, suggesting a possible effect of vitamin E in inhibiting bioreactions due to pyrogen in the dialysate. The classical complement pathway is required in membrane-induced neutrophilic activation, at least during the initial stage.

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“…P2M has a molecular weight of 11,800 and should be cleared more readily by peritone al dialysis than HD using cellulosic membrane dialyzers. It is cleared exclusively by the kidney, glomerular filtra tion and tubular reabsorption, after which it is catabolized within peritubular cells [22], Renal failure does not significantly modify the production of P2M [23], Ogawa et al [24] reported that the presence of novel P2M, but not native P2M, might be related to amyloidogenic predispo sition in HD patients. It is possible that exposure to the dialysis membrane and plastic tubing over a prolonged period of time results in stimulation of immune response in HD patients with eventual amyloid deposition.…”

Section: Discussionmentioning

confidence: 99%

Carpal Tunnel Syndrome in Patients Undergoing CAPD: A Collaborative Study in 143 Centers

Nomoto

Kawaguchi²,

Ohira³

et al. 1995

Am J Nephrol

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Patients undergoing continuous ambulatory peritoneal dialysis (CAPD) who developed carpal tunnel syndrome (CTS) were retrospectively studied in 143 centers in Japan. Among the total 5,050 patients undergoing CAPD between 1980 and 1993 only 7 patients (0.14%) given CAPD developed CTS. Five of these 7 patients treated solely with CAPD developed CTS 12-108 months after starting CAPD. The remaining 2 patients who were initially treated with HD for 7-9 years and then switched to CAPD developed this complication 9 years after starting CAPD. All 7 patients were women, ranging in age from 32 to 70 (average 52) years. We detected the presence of amyloid deposits in 2 of 5 specimens and Β₂-microglobulin in 2 of 4 specimens from these patients. It was concluded that CAPD minimizes the emergence of CTS although constant surveillance is necessary to detect CTS in patients during CAPD.

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Synthesis of ,β2-Microglobulin in Lymphocyte Culture: Role of Hemodialysis, Dialysis Membranes, Dialysis-Amyloidosis, and Lymphokines

Cited by 14 publications

References 25 publications

Rediscovering Beta-2 Microglobulin As a Biomarker across the Spectrum of Kidney Diseases

Rediscovering Beta-2 Microglobulin As a Biomarker across the Spectrum of Kidney Diseases

Reduction of Neutrophil Activation by Vitamin E Modified Dialyzer Membranes

Carpal Tunnel Syndrome in Patients Undergoing CAPD: A Collaborative Study in 143 Centers

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