**10. Discussion and conclusion**

This work aimed to develop and propose a measurable requirement to define the retention properties of the dialyzer being the last line of protection against endotoxins potentially present in the dialysis fluid. By setting out the boundary conditions of the endotoxin load on the feed side and the tolerable endotoxin dose on the patient

side, a requirement could be defined. The requirement employed the concept of the dimensionless logarithmic retention value (LRV). Since protein-free pristine membranes and protein-coated membranes show different endotoxin retention properties, two requirements were developed, one for each case. The requirement for protein-coated membranes is a minimum LRV of 2, and the requirement for proteinfree pristine membranes is a minimum LRV of 1. These requirements are based on the assumption that standard dialysis fluid per ISO 23500-5 [10] can be provided at any time by controlling the water system, the concentrates, and potential ultrafilters in the mixing unit (dialysis monitor). The development of the requirements considered various treatment conditions, where fluid can cross the dialyzer membrane from dialysate to blood side or endotoxins could pass by diffusion from dialysis fluid into the patient's blood. During the development of the requirements, worst-case considerations were employed when specific values were selected from a potential range. Maximum endotoxin concentrations and fluid volumes were assumed—to represent the highest possible endotoxin load—while on the patient side a relatively low body weight was selected. When backfiltration and backdiffusion during a dialysis treatment were taken into account, the hypothetical transfer of all endotoxins across the membrane was considered, which is probably an overestimation to some degree, because a large amount of endotoxins will probably just bypass the membrane in the dialysis fluid stream due to diffusion rate limitations. The proposed endotoxin requirements are realistic for state-of-the-art dialyzers; reference literature supported this for protein-coated membranes [17, 18], and experimental data were presented for protein-free pristine membranes. Even though standard dialysis fluid can be used to perform dialysis therapy according to ISO 23500-1 [15], it also stated that "standard dialysis fluid shall be regarded as the minimum acceptable quality. Ultrapure dialysis fluid is a step forward in improving biocompatibility, reducing inflammation, and preventing dialysis-related complications."
