In the late seventies, convective-based therapies (i.e., Hemofiltration (HF), Hemodiafiltration (HDF) were recognized for their potential clinical benefits (i.e., reduce intradialytic hypotension, improve dialysis tolerance) and increased efficiency on solute removal (i.e., increased removal of middle-sized uremic compounds) compared to conventional hemodialysis (HD) as supportive treatment of end stage kidney disease (ESKD) patients (1-4). Soon after, online HDF emerged as an appealing (5) and viable modality (6) to address main concerns (i.e., disease burden, cardiovascular burden, poor quality of life) associated with current renal replacement modalities including high-flux hemodialysis (7, 8).

HDF has gained, over the last decade, higher clinical acceptance worldwide. As indicated in a recent survey report, HDF has been used to treat 286,000 patients worldwide, of which 278,000 were treated by online HDF (97%) (9). This represents the vast majority of convective therapies (9). Online HDF acceptance is growing faster in the two leading regions (Europe and the Asia Pacific Region including Japan) after having approved the method, with patient average growth rates of 12 to 24% -far above the total patient HD growth rate of 6.6% (9).

Recognizing HDF as an advanced and promising renal replacement modality for end stage kidney disease patients, it is worthwhile to review clinical evidence regarding potential benefits of HDF, as well as  identify gaps and complementary research questions that are needed (10, 11).

In this module, scientific reports were clustered according to the level of evidence and degree of clinical importance (12-14). Three categories have been thus established: the first category consists of short-term prospective studies with a focus on intermediary outcomes (e.g., clinical performances, biological effects); the second category consists of large cohort studies reporting intermediary and/or a hard clinical endpoint (mortality); the third category consists of prospective randomized studies and/or meta-analyses of large studies where HDF was the primary intervention.

References:

1. Baldamus CA, Ernst W, Lysaght MJ, Shaldon S, Koch KM. Hemodynamics in hemofiltration. The International journal of artificial organs. 1983;6(1):27-31.
2. Maggiore Q, Pizzarelli F, Dattolo P, Maggiore U, Cerrai T. Cardiovascular stability during haemodialysis, haemofiltration and haemodiafiltration. Nephrol Dial Transplant. 2000;15 Suppl 1:68-73.
3. van Kuijk WH, Hillion D, Savoiu C, Leunissen KM. Critical role of the extracorporeal blood temperature in the hemodynamic response during hemofiltration. J Am Soc Nephrol. 1997;8(6):949-55.
4. Henderson LW, Silverstein ME, Ford CA, Lysaght MJ. Clinical response to maintenance hemodiafiltration. Kidney Int Suppl. 1975(2):58-63.
5. Leber HW, Wizemann V, Goubeaud G, Rawer P, Schütterle G. Hemodiafiltration: a new alternative to hemofiltration and conventional hemodialysis. Artif Organs. 1978;2(2):150-3.  
6. Canaud B, N’Guyen QV, Lagarde C, Stec F, Polaschegg HD, Mion C. Clinical evaluation of a multipurpose dialysis system adequate for hemodialysis or for postdilution hemofiltration/hemodiafiltration with on-line preparation of substitution fluid from dialysate. Contrib Nephrol. 1985;46:184-6.
7. Blankestijn PJ. Haemodiafiltration: becoming the new standard? Nephrol Dial Transplant. 2013;28(1):1-2.
8. Canaud B, Collins A, Maddux F. The renal replacement therapy landscape in 2030: reducing the global cardiovascular burden in dialysis patients. Nephrol Dial Transplant. 2020;35(Suppl 2):ii51-ii7.
9. Canaud B, Kohler K, Sichart JM, Moller S. Global prevalent use, trends and practices in haemodiafiltration. Nephrol Dial Transplant. 2020;35(3):398-407.
10. Blankestijn PJ, Grooteman MP, Nube MJ, Bots ML. Clinical evidence on haemodiafiltration. Nephrol Dial Transplant. 2018;33(suppl_3):iii53-iii8.
11. Blankestijn PJ, Ledebo I, Canaud B. Hemodiafiltration: clinical evidence and remaining questions. Kidney Int. 2010;77(7):581-7.
12. Milano G. The hierarchy of the evidence-based medicine pyramid: classification beyond ranking. Joints. 2015;3(3):101.
13. Murad MH, Asi N, Alsawas M, Alahdab F. New evidence pyramid. Evid Based Med. 2016;21(4):125-7.
14. Alper BS, Haynes RB. EBHC pyramid 5.0 for accessing preappraised evidence and guidance. Evid Based Med. 2016;21(4):123-5.

P/N 104622-01 Rev A 02/2021