**9. Conclusions**

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

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

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

**survival**

18 Advances in Hemodiafiltration

analysis).

patients on haemodiafiltration.

HV oHDF is a renal replacement treatment modality that is becoming increasingly employed in haemodialysis units worldwide because of a strong body of evidence of its survival benefit over conventional haemodialysis. Optimal substitution volume has become the measure of convective dose, reflecting mainly middle- and large-molecular-weight solutes, and it com‐ pleted former Kt/V that was mainly dedicated to small-molecular-weight solutes. Both dialysis dose components are intent to act synergistically and provide more precise tools for assessing dialysis adequacy. More specifically, convective dose should be tailored to individual patients' needs depending on optimal blood flow rate, rheological blood conditions and the condition of vascular access. Studies in this field are still needed to set the cut-offs of substitution volumes to be adjusted based on the residual renal function. An alternative proposal for dialysis dose is serum beta-2 microglobulin clearance or plasma level determination, but those measure‐ ments are relatively expensive and confounded by calibration differences and variations in the generation rate. The convective volume must be set for each individual patient and should be normalised to a body size-related factor as a surrogate for the convective dialysis dose [26], but given that they varied a lot between the studies, research is still needed to set the required cut-off values in the years to come [23].

## **Acknowledgements**

The authors would like to thank Dr. Aileen Grassmann, Director Clinical and Epidemiological Research, Fresenius Medical Care Deutschland GmbH for having the chapter critically reviewed; Prof. Bernard Canaud and Dipl. Ing. Angelica Kneppel for providing the figures; and Sanja Kozlik, NephroCare Manager, Bosnia and Herzegovina for covering the publication fee.
