FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2000972462> ?p ?o ?g. }

• W2000972462 endingPage "1299" @default.
• W2000972462 startingPage "1297" @default.
• W2000972462 abstract "β2M is a strong and independent indicator of hemodialysis patient outcomes and an excellent surrogate for middle molecules, and deserves to be routinely monitored and incorporated into dialysis adequacy targets. β2M has a double meaning, reflecting both dialysis efficacy in terms of solute mass transfer and patient bioactivity. The work of Ward et al. in this issue warrants a study to test the hypothesis that long daily hemodiafiltration treatment would be the optimal renal replacement modality to improve dialysis patient outcomes. β2M is a strong and independent indicator of hemodialysis patient outcomes and an excellent surrogate for middle molecules, and deserves to be routinely monitored and incorporated into dialysis adequacy targets. β2M has a double meaning, reflecting both dialysis efficacy in terms of solute mass transfer and patient bioactivity. The work of Ward et al. in this issue warrants a study to test the hypothesis that long daily hemodiafiltration treatment would be the optimal renal replacement modality to improve dialysis patient outcomes. In this issue, Ward and coworkers1.Ward R.A. Greene T. Hartmann B. Samtleben W. Resistance to intercompartmental mass transfer limits β2-microglobulin removal by post-dilution hemodiafiltration.Kidney Int. 2006; 69: 1431-1437Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar report an interesting study exploring the barriers to the reduction of circulating β2-microglobulin (β2M) levels in long-term hemodialysis patients. By applying β2M kinetic modeling analysis to a group of dialysis patients, the authors determined that the limitation in β2M mass removal during post-dilution hemodiafiltration (HDF) was mainly due to the patient body mass transfer resistance rather than the hemodiafilter clearance per se. This finding is not really new but is still crucial, as it illustrates the fact that the body clearance is not equivalent to the dialyzer clearance. The difference between body and dialyzer mass transfer rates reflects precisely the β2M mass transfer resistance resulting from the complex interaction of the patient–hemodialysis system. The limitation of the β2M mass removal during an HDF session is due to the high intracorporeal mass transfer resistance that limits the access to β2M stores in the remote poorly perfused compartment. The β2M concentration gradient built during the dialysis session within these two compartments (superficial well-perfused and remote poorly perfused) is referred to as the compartmentalization effect. This apparent sequestration of β2M within the patient's body occurs during high-efficiency HDF and resolves in post-dialysis by the rebound phenomenon. The amplitude of the post-dialysis rebound reflects the intensity of the body concentration disequilibrium generated during the dialysis session. In this context, β2M kinetic modeling analysis appears to be quite helpful in designing the optimal renal replacement modality and in describing the complex behavior of middle-sized and large uremic solutes in hemodialysis patients. In clinical practice, such kinetic analysis may serve also to identify the causes of limitation of the removal of middle-sized solutes in short dialysis treatment schedules.2.Leypoldt J.K. Kinetics of beta2-microglobulin and phosphate during hemodialysis: effects of treatment frequency and duration.Semin Dial. 2005; 18: 401-408Crossref PubMed Scopus (54) Google Scholar Phosphate kinetics is a typical example of such a problem with an acute clinical relevance. Phosphate mass transfer per session remains desperately inadequate despite the extensive use of high-flux membrane and high-efficiency modalities. Limitation of the removal of phosphate is mainly due to its high body mass transfer resistance and is minimally affected by the dialyzer clearance. Reduced body clearance of inorganic phosphate is due to the intracellular and mitochondrial location of this compound. This phenomenon has been well documented in a recent study showing that phosphate kinetics fits a four-compartment model with biphasic concentration changes during high-efficiency dialysis methods.3.Spalding E.M. Chamney P.W. Farrington K. Phosphate kinetics during hemodialysis: evidence for biphasic regulation.Kidney Int. 2002; 61: 655-667Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar Scientific evidence now supports the hypothesis that middle- and large-molecular-weight compounds that accumulate in chronic uremia might contribute to morbidity and mortality of dialysis patients. In the early 1970s, Babb et al. formulated the ‘middle molecules‘ hypothesis to explain some unresolved manifestations of uremia in patients treated by conventional hemodialysis. It was then postulated that the accumulation of middle and large molecules in hemodialysis patients treated with a hemodialyzer with low membrane permeability was responsible for specific complications such as pericarditis and/or neuropathy. Over the past two decades, this fascinating hypothesis has stimulated scientific clinical research and technical improvement in membrane and dialyzer manufacturing. Tremendous work to isolate and identify middle-molecule compounds has been undertaken by several groups, with limited success.4.Bergstrom J. Furst P. Zimmerman L. Uremic middle molecules exist and are biologically active.Clin Nephrol. 1979; 11: 229-238PubMed Google Scholar The complexity of this task has led a group of experts to set up the European Uremic Toxin Work Group (EUTox), dedicated to breaking up and identifying these uremic toxins. At the same time, synthetic highly permeable (high-flux) membranes have been engineered, and hemodialyzers have been designed to increase the clearance of middle- and large-molecular-weight solutes. High-flux membranes reduce significantly the mortality in dialysis patients.5.Chauveau P. Nguyen H. Combe C. et al.Dialyzer membrane permeability and survival in hemodialysis patients.Am J Kidney Dis. 2005; 45: 565-571Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar Enhancement of convective clearances has been applied in the clinic by means of hemofiltration and hemodiafiltration methods in order to increase the removal of large-molecular-weight solutes. Maximizing removal of middle-sized uremic toxins is a new goal that is manifested by the increase in prescription of high-flux hemodialyzers, a practice supported by the recently published European Best Practices Guidelines. This trend was clearly boosted after amyloidosis was diagnosed in long-term hemodialysis patients and β2M was identified as the major component of this amyloid tissue. The toxic role of middle-sized and large compounds in dialysis patients is supported by recent findings of the EUTox group recognizing their heterogeneity and identifying their specific toxicity in uremic patients.6.Vanholder R. Glorieux G. De Smet R. et al.New insights in uremic toxins.Kidney Int Suppl. 2003; 84: S6-S10Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar Among these middle-sized toxins, β2M has emerged as a particularly interesting biomarker of morbidity and mortality in uremic patients.7.Miyata T. Jadoul M. Kurokawa K. Van Ypersele de Strihou C. Beta-2 microglobulin in renal disease.J Am Soc Nephrol. 1998; 9: 1723-1735PubMed Google Scholar β2M is the marker of reference for middle-sized uremic toxins that is used to assess dialyzer performance and treatment efficacy schedule. β2M may be considered as a surrogate for middle molecules in this case. β2M kinetic analysis also provides useful insight into the kinetics of middle and large molecules that are not measurable in the clinic. In this context, blood β2M kinetics should be considered as a complementary tool to optimize treatment schedule, particularly for defining the frequency and duration of sessions. Until recently, β2M was considered a prominent and pathogenic maker for β2M amyloidosis, a severe and disabling complication observed in long-term dialysis patients. The relationship was established on the observation that a gradual rise in blood β2M concentrations occurs in chronic kidney failure patients and that, similarly, the prevalence of β2M amyloidosis increases with years spent on dialysis. This observation supports the fact that β2M and middle molecules accumulate in dialysis patients as a result of the loss of residual kidney function and the low β2M removal of low-flux hemodialysis. Although the exact mechanism by which the circulating β2M tends to deposit in tissue and to polymerize in amyloid fibrils remains unclear, it has been clearly shown that this process requires several chemical modifications of the β2M. The uremic internal milieu, including the chronic microinflammation, the oxidative and carbonyl stress, and the cell phagocytosis defect, offers a quite favorable environment for these modifications.8.Miyata T. Sugiyama S. Saito A. Kurokawa K. Reactive carbonyl compounds related uremic toxicity (“carbonyl stress”).Kidney Int Suppl. 2001; 78: S25-S31Crossref PubMed Google Scholar In other words, the pathogenic role of β2M is correlated not simply to its high blood concentration but rather to the chemical abnormalities of the uremic environment that modify its reactivity. This is a very important finding suggesting that toxicity of β2M is strongly amplified by an environment of inflammation and oxidative stress. High blood β2M concentration has emerged very recently as an independent and strong indicator of poor outcomes in hemodialysis patients. A secondary analysis of the Hemodialysis (HEMO) Study has recently identified that β2M levels predict mortality in hemodialysis patients.9.Cheung A.K. Rocco M.V. Yan G. et al.Serum β-2 microglobulin levels predict mortality in dialysis patients: results of the HEMO Study.J Am Soc Nephrol. 2006; 17: 546-555Crossref PubMed Scopus (337) Google Scholar The relative risk of all-cause mortality increased by 11% per 10-mg-per-liter increase in β2M over a reference value of 27 mg per liter after adjustment for kidney urea clearance and time on dialysis. This study highlights the fact that, in time-dependent Cox regression models, blood β2M levels but not dialyzer β2M clearance are predictive of all-cause mortality. Such an observation means that blood β2M concentrations reflect much more than a passive accumulation of solute due to low β2M dialyzer removal; rather, they are a mixed biomarker reflecting the poor hemocompatibility of the dialysis system, the unfavorable chemical environment, and the periodic cell activation. Interestingly, one can link this observation to the better outcomes recently reported in chronic kidney disease patients treated with highly efficient HDF. Two large cohort studies of hemodialysis patients using Cox regression models have reported that the relative risk of all-cause mortality was reduced by 35%–37% in patients treated with highly efficient HDF as compared with hemodialysis after adjustment for age and main comorbid conditions. By combining high diffusive and convective clearances with a low hemoincompatible profile, HDF offers the best available method to date to reduce circulating β2M levels over a long period of time in dialysis patients. These recent findings suggest that β2M is a strong biomarker of morbidity and mortality in hemodialysis patients. Pre-dialysis blood β2M concentrations provide dual information, both on dialysis efficacy and on internal-milieu bioactivity. Considering all these factors, it is obvious that the β2M kinetic analysis proposed by Ward and coworkers,1.Ward R.A. Greene T. Hartmann B. Samtleben W. Resistance to intercompartmental mass transfer limits β2-microglobulin removal by post-dilution hemodiafiltration.Kidney Int. 2006; 69: 1431-1437Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar based on on-line post-dilution HDF, is very well taken. In this study it is proved that the limitation of β2M mass removal in HDF is mainly due to the intercompartmental mass transfer resistance within the patient and is not a consequence of the low hemodiafilter clearance. This study leaves us with four important messages: First, it confirms that on-line HDF is the most efficient renal replacement therapy method to remove β2M and middle molecules, twice compared with high-flux hemodialysis. Under highly efficient HDF operative conditions, the β2M clearance obtained was 73 ml per minute, which means that the β2M mass removed during the 4-hour session was close to 200 mg per session (600 mg per week). Second, the calculated intracorporeal β2M clearance was 82 ml per minute, a value close to that of the dialyzer clearance. Under these conditions, HDF induces an apparent and progressive sequestration of β2M in the remote poorly perfused compartment. Third, a simple weekly mass balance considering the β2M generation rate (0.136 mg per minute, 1300 mg per week) and the β2M removal rate indicates that the weekly accumulation was close to 700 mg. Fourth, to achieve a zero weekly β2M mass balance in anuric HDF patients, one must change the treatment schedule, by increasing the treatment duration (6 to 8 hours) and/or by increasing the frequency of sessions (daily HDF). Short daily hemofiltration and HDF programs have been evaluated in several studies that have all underlined the power of daily treatment in increasing β2M removal capacity.10.Canaud B. Assounga A. Kerr P. et al.Failure of a daily haemofiltration programme using a highly permeable membrane to return beta 2-microglobulin concentrations to normal in haemodialysis patients.Nephrol Dial Transplant. 1992; 7: 924-930PubMed Google Scholar, 11.Maduell F. Navarro V. Torregrosa E. et al.Change from three times a week on-line hemodiafiltration to short daily on-line hemodiafiltration.Kidney Int. 2003; 64: 305-313Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar Unfortunately, the impact of long daily HDF has not been tested to confirm this hypothesis." @default.
• W2000972462 created "2016-06-24" @default.
• W2000972462 creator A5008299664 @default.
• W2000972462 creator A5052787236 @default.
• W2000972462 creator A5054201980 @default.
• W2000972462 creator A5091602101 @default.
• W2000972462 date "2006-04-01" @default.
• W2000972462 modified "2023-10-15" @default.
• W2000972462 title "β2-microglobulin, a uremic toxin with a double meaning" @default.
• W2000972462 cites W1554800629 @default.
• W2000972462 cites W1913833542 @default.
• W2000972462 cites W1991509112 @default.
• W2000972462 cites W1996669601 @default.
• W2000972462 cites W2012350727 @default.
• W2000972462 cites W2017546730 @default.
• W2000972462 cites W2022224726 @default.
• W2000972462 cites W2064303862 @default.
• W2000972462 cites W2159877216 @default.
• W2000972462 cites W2311976571 @default.
• W2000972462 doi "https://doi.org/10.1038/sj.ki.5000389" @default.
• W2000972462 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16612412" @default.
• W2000972462 hasPublicationYear "2006" @default.
• W2000972462 type Work @default.
• W2000972462 sameAs 2000972462 @default.
• W2000972462 citedByCount "32" @default.
• W2000972462 countsByYear W20009724622012 @default.
• W2000972462 countsByYear W20009724622013 @default.
• W2000972462 countsByYear W20009724622015 @default.
• W2000972462 countsByYear W20009724622016 @default.
• W2000972462 countsByYear W20009724622018 @default.
• W2000972462 countsByYear W20009724622019 @default.
• W2000972462 countsByYear W20009724622020 @default.
• W2000972462 countsByYear W20009724622021 @default.
• W2000972462 countsByYear W20009724622022 @default.
• W2000972462 crossrefType "journal-article" @default.
• W2000972462 hasAuthorship W2000972462A5008299664 @default.
• W2000972462 hasAuthorship W2000972462A5052787236 @default.
• W2000972462 hasAuthorship W2000972462A5054201980 @default.
• W2000972462 hasAuthorship W2000972462A5091602101 @default.
• W2000972462 hasBestOaLocation W20009724621 @default.
• W2000972462 hasConcept C111472728 @default.
• W2000972462 hasConcept C126322002 @default.
• W2000972462 hasConcept C138885662 @default.
• W2000972462 hasConcept C185592680 @default.
• W2000972462 hasConcept C21957315 @default.
• W2000972462 hasConcept C2777367657 @default.
• W2000972462 hasConcept C2778063415 @default.
• W2000972462 hasConcept C2780876879 @default.
• W2000972462 hasConcept C2994496059 @default.
• W2000972462 hasConcept C55493867 @default.
• W2000972462 hasConcept C71924100 @default.
• W2000972462 hasConceptScore W2000972462C111472728 @default.
• W2000972462 hasConceptScore W2000972462C126322002 @default.
• W2000972462 hasConceptScore W2000972462C138885662 @default.
• W2000972462 hasConceptScore W2000972462C185592680 @default.
• W2000972462 hasConceptScore W2000972462C21957315 @default.
• W2000972462 hasConceptScore W2000972462C2777367657 @default.
• W2000972462 hasConceptScore W2000972462C2778063415 @default.
• W2000972462 hasConceptScore W2000972462C2780876879 @default.
• W2000972462 hasConceptScore W2000972462C2994496059 @default.
• W2000972462 hasConceptScore W2000972462C55493867 @default.
• W2000972462 hasConceptScore W2000972462C71924100 @default.
• W2000972462 hasIssue "8" @default.
• W2000972462 hasLocation W20009724621 @default.
• W2000972462 hasLocation W20009724622 @default.
• W2000972462 hasOpenAccess W2000972462 @default.
• W2000972462 hasPrimaryLocation W20009724621 @default.
• W2000972462 hasRelatedWork W1557864465 @default.
• W2000972462 hasRelatedWork W2398464262 @default.
• W2000972462 hasRelatedWork W2406070173 @default.
• W2000972462 hasRelatedWork W2460478490 @default.
• W2000972462 hasRelatedWork W2550998727 @default.
• W2000972462 hasRelatedWork W2607134830 @default.
• W2000972462 hasRelatedWork W2951396236 @default.
• W2000972462 hasRelatedWork W389056650 @default.
• W2000972462 hasRelatedWork W4385877123 @default.
• W2000972462 hasRelatedWork W3112862310 @default.
• W2000972462 hasVolume "69" @default.
• W2000972462 isParatext "false" @default.
• W2000972462 isRetracted "false" @default.
• W2000972462 magId "2000972462" @default.
• W2000972462 workType "article" @default.