New evidence that serum <i>β</i><sub>2</sub>‐microglobulin behaves as a biological marker of bone remodelling in women

Ripoll, Eduardo; Revilla, M.; Hernández, E. R.; Arribas, Ignacio; Villa, L. F.; Rico, H.

doi:10.1111/j.1365-2362.1996.tb02153.x

Cited by 12 publications

(4 citation statements)

References 36 publications

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“…We observed a direct association of serum β2‐M with bone‐cell number by histomorphometry and with serum markers of bone turnover in chronic hemodialysis patients (16). A similar association between β2‐M and indices of bone resorption has been observed in osteoporotic postmenopausal women, in the absence of CKD (17). Whether direct or indirect actions of β2‐M are involved in the formation of the osteoarticular erosions and cysts which are the predilection sites of β2‐M amyloid deposition in dialysis patients remains an unsolved issue.…”

Section: β2‐m—innocent Bystander or Active Player?supporting

confidence: 72%

PROGRESS IN UREMIC TOXIN RESEARCH: Beta2‐Microglobulin

Drüeke

Massy

2009

Seminars in Dialysis

108

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Among the uremic toxins in the "middle molecule" range, beta2-microglobulin (beta2-M) is certainly one of the most frequently studied compounds. Its serum level increases with the progression of chronic kidney disease, to reach very high concentrations in patients with end-stage kidney disease. It is the major protein component of dialysis-related amyloidosis, a dramatic complication which results from high extracellular concentration and posttranslational modification of beta2-M and a number of other promoters of amyloid fibril formation and deposition in osteo-articular tissues. Effective removal of beta2-M can be achieved with highly effective hemodialysis and hemodiafiltration techniques but predialysis session serum levels cannot be normalized. The prevalence and severity of beta2-M amyloidosis appear to have decreased in the last 20 years, although its occurrence may simply be delayed.

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Section: β2‐m—innocent Bystander or Active Player?supporting

confidence: 72%

PROGRESS IN UREMIC TOXIN RESEARCH: Beta2‐Microglobulin

Drüeke

Massy

2009

Seminars in Dialysis

108

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“…11 In addition, serum B2M has been suggested to be a marker of bone remodeling in postmenopausal women. 24,25 Despite this evidence of B2M's putative involvement in bone metabolism, we failed to find a relationship between B2M levels and bone density in our study population. The lack of a relationship may be related to the bone mass measurement sites studied here and/or to the fact that computed tomography (CT) is not an ideal method for evaluating bone density-especially in the absence of a phantom comparator, and certainly does not allow assessment of bone turnover.…”

Section: Discussioncontrasting

confidence: 54%

Plasma beta-2 microglobulin is associated with cardiovascular disease in uremic patients

Liabeuf

Lenglet

Desjardins

et al. 2012

Kidney International

148

111

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Since beta-2 microglobulin (B2M) is a surrogate marker for middle molecular weight uremic toxins and the major protein component in dialysis-related amyloidosis, it has been frequently studied in dialysis patients. It is not known, however, whether B2M has an impact in patients with chronic kidney disease (CKD) not yet on dialysis. Here we studied the relationship of plasma B2M levels to clinical and cardiovascular outcomes in 142 patients (mean age of 67 years) at different stages of CKD. B2M levels increased with CKD stage and thus were highest in hemodialysis patients. Baseline B2M levels were associated with vascular calcification but not with arterial stiffness or bone density. During a mean follow-up of 969 days, 44 patients died and 49 suffered a cardiovascular event. Higher B2M levels were independently associated with overall and cardiovascular mortality and cardiovascular events in the whole cohort and with cardiovascular events in the predialysis cohort. Moreover, B2M appeared to be a better predictor than well-established factors associated with outcomes in this population, such as estimated glomerular filtration rate ((eGFR), only for predialysis patients), inflammation biomarkers, and other factors included in a propensity score. Thus, we confirm the strong relationship between B2M levels and eGFR and confirm the power of B2M to predict overall and cardiovascular mortality and cardiovascular events in patients at different stages of CKD.

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“…In various observational studies both in non-dialyzed [ 320 ] and dialyzed CKD patients [ 321 , 322 , 323 , 324 ] and even in populations not specifically selected because of CKD [ 325 , 326 , 327 ] β 2 -microglobulin has been associated to hard outcomes or to surrogate outcomes like parameters of inflammation [ 323 ], vascular stiffness [ 323 , 324 ] or bone remodeling [ 326 , 327 ]. Although in some of these studies adjustments were made for GFR [ 320 , 325 ], it is difficult to support unequivocally the causative role of β 2 -microglobulin from these data as the concentration of the molecule may sometimes have functioned as a surrogate for (residual) renal function.…”

Section: Middle Moleculesmentioning

confidence: 99%

Biochemical and Clinical Impact of Organic Uremic Retention Solutes: A Comprehensive Update

Vanholder

Pletinck

Schepers

et al. 2018

Toxins

265

303

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Abstract:In this narrative review, the biological/biochemical impact (toxicity) of a large array of known individual uremic retention solutes and groups of solutes is summarized. We classified these compounds along their physico-chemical characteristics as small water-soluble compounds or groups, protein bound compounds and middle molecules. All but one solute (glomerulopressin) affected at least one mechanism with the potential to contribute to the uremic syndrome. In general, several mechanisms were influenced for each individual solute or group of solutes, with some impacting up to 7 different biological systems of the 11 considered. The inflammatory, cardio-vascular and fibrogenic systems were those most frequently affected and they are one by one major actors in the high morbidity and mortality of CKD but also the mechanisms that have most frequently been studied. A scoring system was built with the intention to classify the reviewed compounds according to the experimental evidence of their toxicity (number of systems affected) and overall experimental and clinical evidence. Among the highest globally scoring solutes were 3 small water-soluble compounds [asymmetric dimethylarginine (ADMA); trimethylamine-N-oxide (TMAO); uric acid], 6 protein bound compounds or groups of protein bound compounds [advanced glycation end products (AGEs); p-cresyl sulfate; indoxyl sulfate; indole acetic acid; the kynurenines; phenyl acetic acid;] and 3 middle molecules [β 2 -microglobulin; ghrelin; parathyroid hormone). In general, more experimental data were provided for the protein bound molecules but for almost half of them clinical evidence was missing in spite of robust experimental data. The picture emanating is one of a complex disorder, where multiple factors contribute to a multisystem complication profile, so that it seems of not much use to pursue a decrease of concentration of a single compound.Keywords: uremic toxins; uremic toxicity; uremia; Chronic Kidney Disease; CKD; cardiovascular disease; inflammation; fibrosis; patho-physiology CKD; middle molecules; protein bound uremic solutes; water-soluble uremic solutes Key Contribution: This publication contains a comprehensive overview of the current knowledge on uremic toxicity, as well as an estimation of the degree of toxicity attributed to each individual toxin, and a classification according to the degree of known toxicity.

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New evidence that serum β₂‐microglobulin behaves as a biological marker of bone remodelling in women

Cited by 12 publications

References 36 publications

PROGRESS IN UREMIC TOXIN RESEARCH: Beta2‐Microglobulin

PROGRESS IN UREMIC TOXIN RESEARCH: Beta2‐Microglobulin

Plasma beta-2 microglobulin is associated with cardiovascular disease in uremic patients

Biochemical and Clinical Impact of Organic Uremic Retention Solutes: A Comprehensive Update

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New evidence that serum β2‐microglobulin behaves as a biological marker of bone remodelling in women

Cited by 12 publications

References 36 publications

PROGRESS IN UREMIC TOXIN RESEARCH: Beta2‐Microglobulin

PROGRESS IN UREMIC TOXIN RESEARCH: Beta2‐Microglobulin

Plasma beta-2 microglobulin is associated with cardiovascular disease in uremic patients

Biochemical and Clinical Impact of Organic Uremic Retention Solutes: A Comprehensive Update

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New evidence that serum β₂‐microglobulin behaves as a biological marker of bone remodelling in women