The magnitude of the convection volume and scaling factor that should be delivered to improve outcomes remains a critical question (1,2). This dosing concern should be addressed according to regional practices and patient profiles and should fit with the metabolic needs and haemodynamic tolerance of a patient. 

In Western and European regions, postdilution HDF represents the current practice covering 90% of HDF treated patients. CONTRAST was the first RCT to address this question as it was designed to deliver 24 L of convection volume for a 4-hour treatment. Unfortunately, due to local policy or inadequate training, the median convection volume achieved was only 19.8 L (3,4,5). Post hoc analysis showed that survival was significantly higher in the tertile of patients treated with the highest convection volume, >21.95 L (6). In the Turkish HDF study, a substitution fluid volume of at least 15 L was targeted, and a median substitution fluid volume of 17.2 L was achieved (7). The result was similar to CONTRAST in that no difference in survival could be shown between HDF and HD. Again, a post hoc analysis showed significantly improved survival with convection volumes of >19.9 L (including 2.5 L weight loss) (7). The results of the post hoc analyses from these two RCTs was confirmed by post hoc analysis of the ESHOL study results, which showed that patients treated with a convection volume exceeding 23.1 L per session had significantly improved survival compared to patients treated with high-flux HD (8).

The results of a large dose-finding study performed in an incident population also support a crucial role for convection volume in improving patient outcomes (9). Based on spline curve analysis, a beneficial dose-effect relationship was established with total convection volume as a continuous and independent variable. In addition, an inverse dose-effect relationship was found with serum β₂-microglobulin and CRP concentrations (9). Furthermore, a recent Spanish cohort study using propensity score matching analysis (1012 paired patients) comparing high-flux HD to HDF, showed that HDF-treated patients receiving a median replacement volume of 23.45 (IQ 21.27-25.51) L/session had 24 and 33% reduction in all-cause and cardiovascular mortality respectively (10). 

In Japan  predilution HDF represents the most current practice used in 80 to 90% of HDF treated patients due to vascular access blood flow limitation and regional practices (5,11). Unfortunately, no prospective RCT interventional study is currently available to assess the precise role of convection volume in predilution mode on patient outcome. However, referring to the recent JSDT (Japanese Society for Dialysis Therapy) registry study and more specifically to the spline analysis linking convection volume to patient outcome, one may observe that survival benefits starts at 40 L/session to become optimal at 50 L/session. In other words, predilution convection volume required to improve patient outcome is twice the postdilution volume delivered in European studies. Convective dose required for improving patient survival hold true whatever scaling factor used (i.e., Body Weight, Body-Mass-Index, Total Body Water, or Body Surface Area); using a factor of 2 to account for the predilution mode in Japan provided similar results to the European studies.

In brief, considering all recent study findings, one may consider that an optimal convective dose to improve dialysis patient outcome, based on a thrice weekly treatment schedule in anuric patients, is at least 23 L/session in postdilution mode (26 L/1.73m²) or 46 L/session in predilution mode (52 L/1.73m²). This convective dose target does not apply to specific treatment schedules, such as daily, nocturnal, or incremental dialysis modalities. These treatment options deserve further study in order to evaluate benefits and risks. However, few clinical studies have addressed the effects of increasing treatment time in HDF either by providing longer treatment time (i.e., 8 hrs x 3 weekly) and/or alternate days HDF (12-14). In all cases investigated to date, clinical benefits were observed including better blood pressure and fluid control, better anemia control with ESA dose reduction and better phosphate control, requiring even phosphate supplementation (13).

1. Maduell F. Is There an ‘Optimal Dose’ of Hemodiafiltration? Blood Purif. 2015;40 Suppl 1:17-23
   
2. Canaud B, Koehler K, Bowry S, Stuard S. What Is the Optimal Target Convective Volume in On-Line Hemodiafiltration Therapy? Contrib Nephrol. 2017;189:9-16
3. Canaud B, Kohler K, Sichart JM, Moller S. Global prevalent use, trends and practices in haemodiafiltration. Nephrol Dial Transplant. 2020;35(3):398-407
4. Penne EL, van der Weerd NC, Bots ML, van den Dorpel MA, Grooteman MP, Levesque R, et al. Patient- and treatment-related determinants of convective volume in post-dilution haemodiafiltration in clinical practice. Nephrol Dial Transplant. 2009;24(11):3493-9.
5. Masakane I, Sakurai K. Current approaches to middle molecule removal: room for innovation. Nephrol Dial Transplant. 2018;33(suppl_3):iii12-iii21.
6. Grooteman MP, van den Dorpel MA, Bots ML, Penne EL, van der Weerd NC, Mazairac AH, et al. Effect of online hemodiafiltration on all-cause mortality and cardiovascular outcomes. J Am Soc Nephrol. 2012;23(6):1087-96.
7. Ok E, Asci G, Toz H, Ok ES, Kircelli F, Yilmaz M, et al. Mortality and cardiovascular events in online haemodiafiltration (OL-HDF) compared with high-flux dialysis: results from the Turkish OL-HDF Study. Nephrol Dial Transplant. 2013;28(1):192-202.
8. Maduell F, Moreso F, Pons M, Ramos R, Mora-Macià J, Carreras J, et al. High-efficiency postdilution online hemodiafiltration reduces all-cause mortality in hemodialysis patients. J Am Soc Nephrol. 2013;24(3):487-97.
9. Canaud B, Barbieri C, Marcelli D, Bellocchio F, Bowry S, Mari F, et al. Optimal convection volume for improving patient outcomes in an international incident dialysis cohort treated with online hemodiafiltration. Kidney Int. 2015;88(5):1108-16.
10. Maduell F, Varas J, Ramos R, Martin-Malo A, Pérez-Garcia R, Berdud I, et al. Hemodiafiltration Reduces All-Cause and Cardiovascular Mortality in Incident Hemodialysis Patients: A Propensity-Matched Cohort Study. Am J Nephrol. 2017;46(4):288-97.
11. Watanabe Y, Kawanishi H, Suzuki K, Nakai S, Tsuchida K, Tabei K, et al. Japanese society for dialysis therapy clinical guideline for “Maintenance hemodialysis: hemodialysis prescriptions”. Ther Apher Dial. 2015;19 Suppl 1:67-92.
12. Cornelis T, van der Sande FM, Eloot S, Cardinaels E, Bekers O, Damoiseaux J, et al. Acute hemodynamic response and uremic toxin removal in conventional and extended hemodialysis and hemodiafiltration: a randomized crossover study. Am J Kidney Dis. 2014;64(2):247-56.
13. Maduell F, Ojeda R, Arias-Guillen M, Rossi F, Fontseré N, Vera M, et al. Eight-Year Experience with Nocturnal, Every-Other-Day, Online Haemodiafiltration. Nephron. 2016;133(2):98-110.
14. Maduell F, Navarro V, Torregrosa E, Rius A, Dicenta F, Cruz MC, et al. Change from three times a week on-line hemodiafiltration to short daily on-line hemodiafiltration. Kidney Int. 2003;64(1):305-13.

    P/N 104622-01 Rev A 02/2021