**8. The impact of substitution volume in haemodiafiltration on patients' survival**

In the era of convective treatment modalities employed in oHDF, the substitution volume appears to be critical for patient survival in prevalent patients [14, 41–43]. The Dialysis Outcomes and Practice Patterns Study (DOPPS) showed better survival of prevalent patients with high-volume HDF defined as having a substitution fluid volume of >15 L compared to low-flux HD (RR 0.65) [14]. The Turkish RCT and the CONTRAST RCT revealed survival benefits of oHDF over conventional HD in prevalent patients with 17.4 L (RR 0.54) and 21.95 L (RR 0.61) of substitution and convective volumes, respectively, but only in post hoc analyses [41, 42]. The first positive RCT in favour of improved survival of oHDF over conventional HD was the ESHOL study which showed convective volumes cut-offs of 23.1–25.4 L (RR 0.60) and >25.4 L (RR 0.55) in the intermediate and upper tertiles, respectively, also in post hoc analysis of prevalent patients' data [43]. Eventually, the observational Balkan study in incident HD patients conducted in Bosnia and Herzegovina, Serbia and Slovenia, while using European Clinical Database (EuCliD®), [17] showed the lowest RR for mortality of 0.29 on high-volume oHDF compared to high-flux conventional HD. The substitution volume cut-off of 20.4 L was discriminating between low- and high-volume oHDF, which makes the convective volume at least in the range of the one achieved in ESHOL study. Consequently, overall negative correlation may be observed between increasing ultrafiltration volumes and mortality risks in patients on convective-based treatments in comparison with conventional HD. **Figure 13** shows descriptive hazard ratios for mortality based on literature data (not on forest-plot analysis).

**Figure 13.** Negative correlation between increasing ultrafiltration volumes and decreasing relative risk of mortality in patients on haemodiafiltration.

Recently, Canaud et al. aimed at determining optimal convection volume in 2293 international incident dialysis patients treated for 4 h with oHDF in post-dilution mode. Two-year survival rate was found to increase at about 55 L of convection volume per week and to stay increased up to about 75 L/week [44].
