UNRESOLVED ISSUES IN DIALYSIS: Extracorporeal Strategies for the Removal of Middle Molecules

Abstract

Uremic toxins with a molecular weight of less than 500 Da are classified as small nitrogenous waste products. They are highly water soluble, relatively homogeneous, and have no protein binding. Other uremic retention toxins differ significantly from the small nitrogenous metabolite class in molecular weight, heterogeneity, protein binding, and hydrophobicity. The European Uremic Toxin Work Group subdivided molecules into two categories: protein-bound solutes and middle molecules. Middle molecules were defined as toxins in the molecular weight range of 500-60,000 Da, which exceeds the molecular weight of 2000 Da defined in the original middle molecule hypothesis. Under this new proposed definition, most of these middle molecules are low molecular weight peptides and proteins (LMWPs). This concise review focuses on LMWPs. The metabolism of LMWPs is described, including molecular weight, physical conformation, and charge. Factors influencing dialytic removal of LMWPs such as membrane characteristics, protein-membrane interactions, and solute removal mechanisms, as well as strategies to enhance clearance of these compounds are discussed.

Biocompatibility of modified polyethersulfone membranes by blending an amphiphilic triblock co-polymer of poly(vinyl pyrrolidone)–b-poly(methyl methacrylate)–b-poly(vinyl pyrrolidone)

“…However, it is difficult to remove middle molecular weight toxins (such as b 2 -microglobulin (b 2 -M)) during conventional hemodialysis. b 2 -M, which is considered one of the middle molecular weight toxins for end-stage renal disease patients [76], is a non-glycosylated protein with a molecular weight of 11,800 Da. Free b 2 -M is found in the body fluids as a result of shedding from cell surfaces or intracellular release [77,78].…”

Dynamics of Changes in Heart Conduction System in Dialyzed Young Adults After Kidney Transplantation—Pilot Study

“…These pathophysiologic processes ongoing in the heart of patients with CKD could also be involved in slowing down or even halting the intraventricular electrical impulses propagation. As Winchester reported, development of disorders in the conduction system of the heart in CKD patients, could result from accumulation not only of uremic toxins, but also of endothelin-1, tumor necrosis factor a, leptin, interleukin-1a, interleukin-6, or parathormone [17]. The accompanying, biochemical shifts, typical for the secondary hyperparathyroidism in the population of CKD patients, are coresponsible for the intraventricular conduction disorders, as presented on the isochrone maps.…”

Sodium potassium adenosine triphosphatase (Na/K-ATPase) as a therapeutic target for uremic cardiomyopathy

“…Additionally, the uremic state itself appears to result in the transactivation of downstream signaling events that induce cardiomyocyte enlargement and cardiac fibroblast proliferation which account for the process of cardiac [11,30,31]. …”