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Middle Molecules (middle + molecule)
Selected AbstractsBack to the Future: Middle Molecules, High Flux Membranes, and Optimal DialysisHEMODIALYSIS INTERNATIONAL, Issue 1 2003Raymond C. Vanholder Middle molecules can be defined as compounds with a molecular weight (MW) above 500 Da. An even broader definition includes those molecules that do not cross the membranes of standard low-flux dialyzers, not only because of molecular weight, but also because of protein binding and/or multicompartmental behavior. Recently, several of these middle molecules have been linked to the increased tendency of uremic patients to develop inflammation, malnutrition, and atheromatosis. Other toxic actions can also be attributed to the middle molecules. In the present publication we will consider whether improved removal of middle molecules by large pore membranes has an impact on clinical conditions related to the uremic syndrome. The clinical benefits of large pore membranes are reduction of uremia-related amyloidosis; maintenance of residual renal function; and reduction of inflammation, malnutrition, anemia, dyslipidemia, and mortality. It is concluded that middle molecules play a role in uremic toxicity and especially in the processes related to inflammation, atherogenesis, and malnutrition. Their removal seems to be related to a better outcome, although better biocompatibility of membranes might be a confounding factor. [source] Prospective Evaluation of the Change of Predialysis Protein-Bound Uremic Solute Concentration With Postdilution Online HemodiafiltrationARTIFICIAL ORGANS, Issue 7 2010Natalie Meert Abstract Although protein-bound uremic compounds have been related to outcome in observational studies, few current dialysis strategies provide more removal of those compounds than standard hemodialysis. We evaluated the evolution of protein-bound uremic solutes after a switch from high-flux hemodialysis to postdilution hemodiafiltration (n = 13). We compared predialysis solute concentration at 4, 5, and 9 weeks versus baseline for several protein-bound compounds and water-soluble solutes, as well as for ,2 -microglobulin. After 9 weeks of postdilution hemodiafiltration, a significant decrease versus baseline could be detected for total concentration of protein-bound solutes: p-cresylsulfate (3.98 ± 1.51,3.17 ± 1.77 mg/dL, ,20%, P < 0.01) and 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid (0.72 ± 0.52,0.64 ± 0.46 mg/dL, ,11%, P < 0.01). For the other protein-bound solutes, hippuric acid, indoleacetic acid, and indoxylsulfate, no change in total concentration could be detected. The concentration of the middle molecule, ,2 -microglobulin, decreased as well after 9 weeks of postdilution hemodiafiltration (24.7 ± 9.3,18.1 ± 6.7 mg/L, ,27%, P < 0.01). For water-soluble compounds, no significant change of concentration was found. Postdilution hemodiafiltration in comparison to high-flux hemodialysis provided significant reduction of predialysis concentration of protein-bound compounds, especially those with the highest protein binding, and of ,2 -microglobulin, by ,11 to ,27% in 9 weeks. [source] Alternatives to standard hemodialysisHEMODIALYSIS INTERNATIONAL, Issue 2007Mark S. MACGREGOR Abstract Survival of patients on hemodialysis remains poor, but the benefits of increasing urea clearance have probably been maximized within our current treatment schedules. Long dialysis sessions (8 hr) produce impressive outcomes, with mortality 53% to 55% lower than conventional schedules. Even increasing from 4 to 5 hr may improve survival. Increased frequency of dialysis (6 times weekly) produces impressive reductions in left ventricular mass and could conceivably be implemented in-center. Preliminary data suggest a 61% reduction in mortality with increased frequency. Nightly dialysis combines longer sessions with increased frequency and has produced remarkable clinical gains in blood pressure, left ventricular mass, serum phosphate, and sleep apnea. However, the data are mainly from case series and impact on mortality remains unknown. Expansion of home hemodialysis would be necessary for this modality to grow. Convective therapies remove middle molecules more effectively, and observational data suggest hemodiafiltration has the potential to improve mortality by 35% to 36%. Hemodiafiltration has the advantage of being relatively easy to implement. The uremic milieu is complex and further investigation of the underlying pathophysiology is needed to inform future dialysis interventions. The survival data above are from observational studies, and hence benefits are likely to be exaggerated. Randomized trials of dialysis interventions are desperately needed. They remain difficult to perform, because of the complexity of both the patient population and the interventions, and because of limited available funding. [source] Uremic Toxins: Removal with Different TherapiesHEMODIALYSIS INTERNATIONAL, Issue 2 2003Raymond C. Vanholder A convenient way to classify uremic solutes is to subdivide them according to the physicochemical characteristics influencing their dialytic removal into small water-soluble compounds (<500 Da), protein-bound compounds, and middle molecules (>500 Da). The prototype of small water-soluble solutes remains urea although the proof of its toxicity is scanty. Only a few other water-soluble compounds exert toxicity (e.g., the guanidines, the purines), but most of these are characterized by an intra-dialytic behavior, which is different from that of urea. In addition, the protein-bound compounds and the middle molecules behave in a different way from urea, due to their protein binding and their molecular weights, respectively. Because of these specific removal patterns, it is suggested that new approaches of influencing uremic solute concentration should be explored, such as specific adsorptive systems, alternative dialytic timeframes, removal by intestinal adsorption, modification of toxin, or general metabolism by drug administration. Middle molecule removal has been improved by the introduction of large pore, high-flux membranes, but this approach seems to have come close to its maximal removal capacity, whereas multicompartmental behavior might become an additional factor hampering attempts to decrease toxin concentration. Hence, further enhancement of uremic toxin removal should be pursued by the introduction of alternative concepts of elimination. [source] Back to the Future: Middle Molecules, High Flux Membranes, and Optimal DialysisHEMODIALYSIS INTERNATIONAL, Issue 1 2003Raymond C. Vanholder Middle molecules can be defined as compounds with a molecular weight (MW) above 500 Da. An even broader definition includes those molecules that do not cross the membranes of standard low-flux dialyzers, not only because of molecular weight, but also because of protein binding and/or multicompartmental behavior. Recently, several of these middle molecules have been linked to the increased tendency of uremic patients to develop inflammation, malnutrition, and atheromatosis. Other toxic actions can also be attributed to the middle molecules. In the present publication we will consider whether improved removal of middle molecules by large pore membranes has an impact on clinical conditions related to the uremic syndrome. The clinical benefits of large pore membranes are reduction of uremia-related amyloidosis; maintenance of residual renal function; and reduction of inflammation, malnutrition, anemia, dyslipidemia, and mortality. It is concluded that middle molecules play a role in uremic toxicity and especially in the processes related to inflammation, atherogenesis, and malnutrition. Their removal seems to be related to a better outcome, although better biocompatibility of membranes might be a confounding factor. [source] | ||||||||||