**3. The effect of blood on dialyzer performances**

When blood enters the HD system *via* the arterial line, a complex interplay of factors alters membrane performances *e.g.* clearances, ultrafiltration rates and sieving coefficients. These factors are patient- and system- dependent.

### **3.1 Patient-dependent factors**


#### **3.1.4 System-dependent factors**

3.1.4.1 Several factors are here involved such as the **vascular access flow rate**, and **the pump rate** and the response of the dialyzer depending on the membrane resistance and geometry. As seen from a kinetic perspective, the blood flow, and pressures are on-off events which are reflected in a "push-pull" effect on the dialyzer hollow fibre. Although these effects are still not completely known, they seem to be relevant on the shear rates, the erythrocyte orientation, leading in the worst conditions to predispose to their agglutination and clogging of the hollow fibre. Calculating clearances, ultrafiltration rates and sieving coefficient using aqueous solution can lead to an overestimate of 30%and is therefore hardly informative of the dialyzer behaviour in vivo. Finally, it was shown that sieving coefficients may change over the time of treatment rendering the calculation of clearances on the basis of the quantization of urea on the ultrafiltrate may also lead to an overestimation of the dialyzer performances (Claure-Del Granado et al., 2010).

Many soluble mediators are produced and released following the blood-membrane interaction. Products of the phospholipase A2 such as platelet-activating factor (PAF) and leukotrienes are released by the direct interaction of PMNs and platelets with complementactivating membranes. Although in the presence of blood, the mechanisms of production of PAF and leukotrienes can not be readily differentiated from the activation, as they follow the same kinetics, we could show that for PAF for example, its production and release could be observed in complement-independent conditions such as in the absence of plasma by purified cells incubated with flat HD membranes (Tetta et al., 1996). A large number of studies have also suggested the occurrence in the plasma of lytic enzymes normally present in the vacuoles of inflammatory cells such as elastases, and metalloenzymes. The release of these lytic enzymes is caused by a phenomenon named by cell physiologists as "frustrated

When blood enters the HD system *via* the arterial line, a complex interplay of factors alters membrane performances *e.g.* clearances, ultrafiltration rates and sieving coefficients. These

**3.1.1 Albumin**: Relevant amount of albumin fragments are detectable in the serum of patients undergoing HD. Uremia appears to facilitate the fragmentation of albumin and/or the retention of albumin fragments in blood (Donadio et al., 2009). Depending on their molecular weight, albumin fragments may be either lost in the dialysate or remain trapped in the wall of the hollow fibre. More in general, plasma proteins may

**3.1.2 Plasma viscosity** which is related (but not exclusively) to albumin, fibrinogen and lipids. **3.1.3 Free hemoglobin:** *In vitro* data have shown that blood circulation produces an increase of up to 280% in free hemoglobin levels and an increase of 320% in electronegative LDL (LDL(-) subfraction, a highly atherogenic form of oxidized LDL. The significant correlation between LDL(-) and free hemoglobin levels shows the oxidative activity of

3.1.4.1 Several factors are here involved such as the **vascular access flow rate**, and **the pump rate** and the response of the dialyzer depending on the membrane resistance and geometry. As seen from a kinetic perspective, the blood flow, and pressures are on-off events which are reflected in a "push-pull" effect on the dialyzer hollow fibre. Although these effects are still not completely known, they seem to be relevant on the shear rates, the erythrocyte orientation, leading in the worst conditions to predispose to their agglutination and clogging of the hollow fibre. Calculating clearances, ultrafiltration rates and sieving coefficient using aqueous solution can lead to an overestimate of 30%and is therefore hardly informative of the dialyzer behaviour in vivo. Finally, it was shown that sieving coefficients may change over the time of treatment rendering the calculation of clearances on the basis of the quantization of urea on the ultrafiltrate may also lead to an

overestimation of the dialyzer performances (Claure-Del Granado et al., 2010).

**2.3.1 Soluble mediators** 

phagocytosis".

**3. The effect of blood on dialyzer performances** 

cause a phenomenon names as "protein fouling".

free hemoglobin (Ziouzenkova et al., 1999) (**Figure 3**).

factors are patient- and system- dependent.

**3.1 Patient-dependent factors** 

**3.1.4 System-dependent factors** 

Fig. 3. Microhemolysis is the release of small quantities of hemoglobin (micro- or nanomolar) from erythrocytes. The tyrosine of a hemoglobin molecule can undergo a transition to a reactive free radical. This can react with other protein tyrosine residues to form a dityrosine molecule. Microhemolysis occurs during the HD procedure in which the erythrocytes are slightly damaged and tend to "leak" very small quantities of hemoglobin. This is a very common phenomena in HD and should not be confused with gross hemolysis.
