**5. Rational for improved patients' survival on high-volume haemodiafiltration**

The European Dialysis Working Group (EUDIAL) performed a systematic review and metaanalysis of randomised controlled trials on haemodiafiltration in 2014 and found the beneficial effect of post-dilution oHDF over HD in reducing all-cause and cardiovascular mortality (pooled RR-0.84; 95% CI, 0.73–0.96) and recommended wide acceptance of this treatment modality [23]. EUDIAL recommends the adoption of effective convective volume as a key quantifier for HDF. Providing time is constant and anticoagulation is adequate, limiting factors for high-volume haemodiafiltration (i.e. the amount of substitution fluid produced) are blood viscosity, filter performance and blood flow rate.

#### **5.1. Limiting factors for high-volume on-line haemodiafiltration**

#### *5.1.1. Blood viscosity as a limiting factor for high-volume on-line haemodiafiltration*

It is not only that FF from **Figure 3** accounts for the proportion of UF volume in the blood volume, but in reality, FF is even higher, because UF volume comes from plasma water, not from the whole blood. **Figure 6** shows the example of a patient with FF of 0.30 (UF rate 120 ml/ min and blood flow rate 400 ml/min). However, if the haematocrit of this patient is 30%, it means that his/her plasma water flow is only 280 ml/min, which increases FF to 0.43 (**Figure 6**).

**Figure 6.** Increased filtration fraction in plasma water.

Consequently, too much convective volume increases the risk of haemoconcentration, thereby compromising the fine balance between the two by interfering with membrane permeability both on hydraulic and solute fluxes.

#### *5.1.2. Filter performance as a limiting factor for high-volume on-line haemodiafiltration*

The efficiency of HDF might be improved by increasing the size of the surface area of the membranes (provided optimal blood flow was achieved), so that high efficiency might be achieved with a surface area of 2.2 m2 , as opposed to the standard surface of 1.4 m2 , thereby allowing much more substitution fluid to be replaced at a rate of 120 ml/min in post-dilution mode, in contrast to 60 ml/min which was achieved with standard surface [24].

The size of a membrane pore dictates the sieving coefficient (SC) of a substance to be removed. The higher the sc, the higher the UF and clearance of a particular solute. The reduction ratios of beta-2 microglobulin with low-flux, high-flux haemodialysis and HDF are 20, 60 and 75% per session, respectively [25]. The EUDIAL group, nominated by the European Renal Associ‐ ation – European Dialysis and Transplant Association (ERA–EDTA), set the SC for beta-2 microglobulin at minimum of 0.6 [26] in high-flux filters (which are mandatory with HDF). However, in order to achieve the optimal outcome for the patients, filters are nowadays designed with even higher SC for beta-2 microglobulin of 0.8 for efficient elimination, but still retention of albumin (**Figure 7**).

effect of post-dilution oHDF over HD in reducing all-cause and cardiovascular mortality (pooled RR-0.84; 95% CI, 0.73–0.96) and recommended wide acceptance of this treatment modality [23]. EUDIAL recommends the adoption of effective convective volume as a key quantifier for HDF. Providing time is constant and anticoagulation is adequate, limiting factors for high-volume haemodiafiltration (i.e. the amount of substitution fluid produced) are blood

It is not only that FF from **Figure 3** accounts for the proportion of UF volume in the blood volume, but in reality, FF is even higher, because UF volume comes from plasma water, not from the whole blood. **Figure 6** shows the example of a patient with FF of 0.30 (UF rate 120 ml/ min and blood flow rate 400 ml/min). However, if the haematocrit of this patient is 30%, it means that his/her plasma water flow is only 280 ml/min, which increases FF to 0.43 (**Figure 6**).

Consequently, too much convective volume increases the risk of haemoconcentration, thereby compromising the fine balance between the two by interfering with membrane permeability

The efficiency of HDF might be improved by increasing the size of the surface area of the membranes (provided optimal blood flow was achieved), so that high efficiency might be

allowing much more substitution fluid to be replaced at a rate of 120 ml/min in post-dilution

The size of a membrane pore dictates the sieving coefficient (SC) of a substance to be removed. The higher the sc, the higher the UF and clearance of a particular solute. The reduction ratios

, as opposed to the standard surface of 1.4 m2

, thereby

*5.1.2. Filter performance as a limiting factor for high-volume on-line haemodiafiltration*

mode, in contrast to 60 ml/min which was achieved with standard surface [24].

viscosity, filter performance and blood flow rate.

12 Advances in Hemodiafiltration

**Figure 6.** Increased filtration fraction in plasma water.

both on hydraulic and solute fluxes.

achieved with a surface area of 2.2 m2

**5.1. Limiting factors for high-volume on-line haemodiafiltration**

*5.1.1. Blood viscosity as a limiting factor for high-volume on-line haemodiafiltration*

**Figure 7.** Solute membrane permeability: higher sieving coefficient for beta-2 microglobulin.

Correlation between ultrafiltered volume and beta-2 microglobulin elimination is linear, as specified by Lornoy et al. (**Figure 8**) [27].

**Figure 8.** A linear function of ultrafiltered volume and beta-2 microglobulin elimination. HDF, haemodiafiltration (with permission of authors).

Enhanced clearances of middle molecules such as beta-2 microglobulin [28] and phosphate [29] and other small molecules, such as homocysteine and complement D factor [30] are the main biochemical benefits of convective-based treatment over conventional HD.

#### *5.1.3. Blood flow as a limiting factor for high-volume haemodiafiltration*

On-line monitoring of blood parameters allows adjustment of ultrafiltration rate to identify the patient-specific exchange rate possible at any given point in time while enabling haemo‐ dynamic stability. The substitution rate is adjusted to blood flow rate, thereby controlling haemoconcentration, whereas blood flow rate is adjusted to dialysis flow rate to control diffusion [31] (as for the diffusion component on-line clearance monitoring is used and the goal is to achieve spKt/V of 1.4). Therefore, if the blood flow rate drops from 100 L to 70 L per session, and the total UF volume remains at 25 L, the filtration fraction rises from 25% to 37% (**Figure 9**), which may generate a lot of difficulty during the session, lot of alarms and lot of critical TMP notifications, and the session may not end with a volume that was targeted.

**Figure 9.** The impact of blood flow on filtration fraction.
