**7. How much endotoxin must a dialyzer be able to retain?**

Two boundary conditions were defined in the previous sections: the endotoxin load on the dialysate side and the non-pyrogenic dose on the blood side. The dialyzer membrane must reduce the endotoxin load on the dialysate side to a non-pyrogenic level on the blood side. With the help of these two boundary conditions, a minimum LRV can be calculated for a dialysis membrane. Since protein-free pristine membranes are different from protein-coated membranes, two requirements can be developed for either case. In the first step, the requirement for a protein-coated membrane will be developed. In the second step, the requirement for the pristine membrane is derived. In the following calculations, the use of standard dialysis fluid will be assumed as worst-case, and the accumulated effects of online bolus, backfiltration/ backdiffusion, and online rinse-back are concentrated into 1-hour treatment.

**Figure 1** shows the dose calculation for the 1-hour treatment case using standard dialysis fluid of 0.5 EU/ml. Fluid volumes for online bolus and rinse-back are assumed to be 500 ml each. The volume assumed for backfiltration or backdiffusion was derived from a blood flow rate of 600 ml/min being the limiting factor for endotoxin transfer irrespective of the mass transport mechanism; therefore, the volume is 600 ml/min × 60 min = 36 L. The endotoxin amount at each step is calculated as 0.5 EU/ml × fluid volume. This results in 250 EU, 18000 EU, and 250 EU for online bolus, backfiltration/ backdiffusion, and online rinse-back, respectively, producing a total of 18500 EU in 1 hour. The minimum LRV (rounded up to 1 significant digit) for the protein-coated membrane to reduce 18500 EU below 250 EU is LRV 2. The dose threshold of 250 EU was calculated using the limits of 5 EU/kg/hour for a 50 kg person as 5 EU/kg/hour x 50 kg × 1 hour = 250 EU. A protein-coated membrane with an LRV of 2 reduces the endotoxin load of 18500 EU on the dialysate side to 185 EU on the blood side.

**Figure 2** shows in summarized form the dose calculation when combining the 1-hour treatment case as described above with the online-priming situation with a pristine

#### **Figure 1.**

*Calculation of endotoxin load on the feed side, LRV, and endotoxin dose on the filtrate (patient) side for treatment cases, where a protein-coated membrane, reduces the transfer of endotoxins from the standard dialysis fluid.*

#### **Figure 2.**

*Calculation of endotoxin load on the feed side, LRV, and endotoxin dose on the filtrate (patient) side for treatment cases, where a protein-coated membrane (right side) and a pristine membrane (left side), reduces the transfer of endotoxins from the standard dialysis fluid.*

membrane. The volume of online-priming fluid infused into the patient was assumed to be 500 ml. The endotoxin amount of online priming calculates as 0.5 EU/ml x 500 ml = 250 EU. The dose threshold of 65 EU for online priming can be calculated as the total dose threshold of 250 EU (calculated with the limit of 5 EU/kg/hour for a 50 kg person) minus 185 EU covering online bolus, backfiltration/backdiffusion, and online rinseback. The minimum LRV (rounded to one significant digit) for the pristine membrane to reduce 250 EU below 65 EU is LRV 1. A pristine membrane with an LRV of 1 reduces the endotoxin load of 250 EU on the dialysate side to 25 EU on the blood side.

#### **Figure 3.**

*Calculation of endotoxin load on the feed side, LRV, and endotoxin dose on the filtrate (patient) side for treatment cases, where a protein-coated membrane (right side) and a pristine membrane (left side), reduces the transfer of endotoxins from ultrapure dialysis fluid.*

**Figure 3** shows a dose calculation for a 1-hour treatment case analogous to the calculations shown in **Figure 2**. The only difference is that the use of ultrapure dialysis fluid of 0.03 EU/ml was assumed instead of standard dialysis fluid. The minimum LRV of the protein-coated membrane would need to be LRV 1 in order to reduce 1110 EU to 111 EU. The pristine membrane would not need to have endotoxin retention properties at all during online priming. The total endotoxin dose of 126 EU (111 EU + 15 EU= 126 EU) would be below the endotoxin dose limit of 250 EU (5 EU/kg/hour for a 50 kg patient).
