**2. What are endotoxins and can endotoxin retention requirements be inferred from other dialyzer properties?**

Endotoxins are mainly lipopolysaccharides (LPS) originating as fragments of bacterial cell membranes. The dominant bacterial source is gram-negative bacteria, which possess an LPS-rich outer membrane. A chemical feature of LPS is their amphiphilic character, which means the molecules combine hydrophilic and hydrophobic parts. This amphiphilic character enables the LPS to form supramolecular structures and biological entities, such as micelles, vesicles, or cell membranes. In those structures, the hydrophobic lipid parts bind together to avoid interaction with water while the hydrophilic polysaccharide parts are exposed to the hydrophilic aqueous environment. This chemical behavior takes place in dialysis fluid and aqueous solutions, in general. More on endotoxins can be found in work done by Williams [1] and Bishop [2].

Dialyzers are primarily designed to remove water and uremic toxins from a patient's blood, and design specifications typically address those requirements. Chemically, uremic toxins are distinctly different from LPS molecules. Uremic toxins are small molecules or proteins that accumulate in the patient's blood when kidney function is impaired. Uremic toxins, even though diverse in chemical nature, are commonly water-soluble in most cases; therefore, do not form larger, aggregated structures in blood plasma water. Water-insoluble uremic toxins bind to albumin, which makes them water-soluble in the albumin-bound form, and they are then called protein-bound uremic toxins.

Dialyzer specifications, such as clearance, sieving coefficient, or ultrafiltration coefficient, as defined and required by technical standards, such as ISO 8637-1 [3], specify the ability to remove water or uremic toxins. Due to the distinct differences in chemical nature and chemical environment of LPS vs. uremic toxins, endotoxin retention properties cannot be simply inferred from specifications describing uremic toxin removal but rather need to be described and investigated in their specific way.
