This document discusses haemodialysis versus haemodiafiltration (HDF) for end-stage renal disease therapy. It provides historical context on the development of dialysis. It describes how HDF combines diffusion and convection to clear small molecules as well as middle and larger molecules like beta-2 microglobulins that standard haemodialysis cannot. Several studies comparing HDF and haemodialysis are summarized that have had mixed results, with some showing benefits of HDF like reduced symptoms and beta-2 microglobulin levels but not clear improvements in mortality. For HDF to provide benefits, a minimum convective volume of 20 litres per session is recommended. Barriers to wider adoption of HDF include cost and infrastructure requirements.

1. Haemodialysis
OR
Haemodifiltration?
By
Mohsen El Kossi
Consultant Renal Physician
Doncaster Royal Infirmary

4. Current ESRD Therapy
 Delivers 10-15% GFR equivalency
 Is pro-inflammatory
 Is intrusive on patient life-style
 Is associated with significant intradialytic
complications and interdialytic symptoms

5. Benjamin Burton (1976)
“Maintenancedialysis on the wholeis non-physiological
andcan bejustifiedonly because of the finiteness of its
alternative.”

6. Historical Background
• 1913:
– John J. Abel first dialysis attempt on animals.
• 1924:
– Georg Haas: first dialysis attempt in human, 6
patients and all died.
• 1945:
– Kolf: first 15 patients died, but the 16th, survived
after 11 hours of dialysis.

7. Recent Technological Advances in
RRT
High efficiency/high flux membranes
Biocompatible membranes
Alterations in internal dialyzer geometry to
increase efficiency
On-line replacement solution production
for continuous therapies for AKI or
hemofiltration for ESRD
On-line monitoring of dialysis dose and
vascular access function

8. Is There Any Achievement?

9. HD & HDF
• Introduced in 1970s (Henderson et al 1974 &
Leber et al 1978).
• It combines both diffusion and convection.
• HD: mainly diffusion, hence effective for small
size molecules (urea, electrolytes, acid base,
water correction).
• HDF: convection, middle and larger size
molecules (e.g. B2 microglobulins)

10. Dialysis versus Haemofiltration

11. Glomerular UF and HDF
IGP
1
U
U
2
U
Re-absorption
3
1
2
3

12. Water in HD & HDF

13. Technical Aspects

14. Dialysis Quality
• High Flux (amount of water transfer):
– Low flux: Kuf <10 mL/h/mmHg
– High flux: Kuf >20 mL/h/mmHg
– B2 microglobulin clearance of 20ml/min
• High Efficiency (urea clearance):
– Low efficiency: KoA <500 mL/min
– High efficiency: KoA >600 mL/min
– Urea clearance rate > 210 mL/min

15. Clearance and Survival

16. Once upon a time in dialysis: the
last days of Kt/V?
Vanholder et al 2015

17. Theoretical Advantages
of HDF

18. Examples of Uremic Toxins

19. Other Middle Molecules Cleared
by HDF

20. Effect of RRT on Clearance

21. B2 microglobulin

22. Anaemia and HDF

23. Theoretical Advantages of HDF

24. Clinical Evidence
HDF versus HD

25. Wizemann et al 2000
• HDF vs low flux HD.
• Limited number (44).
• Negative outcome (only reduction of B2
microglobulins).

26. Schiffl 2007
• HDF vs high flux HD.
• Limited number (76).
• Cross over RCT each modality for 24 month.
• Negative outcome in terms of mortality.
• Kt/V and B2 microglobulins were better with
HDF.

27. Canaud et al 2006 (DOPPS)
• Adequate number (2165).
• 4 Groups, low flux HD, low efficiency HDF, high
flux, high efficiency HDF.
• Observational study with inherent selection
bias.
• Better survival with high efficiency HDF, (RR
0.65).

28. Locatelli et al 2010
• HDF/HF vs low flux HD.
• Limited number (40/36/70).
• Outcome is stable intradialytic blood pressure
in convective therapy vs HD.
• Significant increase of predialysis systolic BP in
HDF compared to HD and HF (+4.2/-0.6/-1.8
mmHg).

29. Grootenman et al 2012
(CONTRAST Trial)
• OL-HDF vs low flux HD RCT
– Adequate number (714).
– Negative outcome in terms of all cause mortality.
– For the first time it highlighted the importance of
the convective volume (>20 litres/session).

31. OK et al 2012
(Turkish Trial)
• OL-HDF vs high flux HD RCT.
• Adequate number (782).
• Negative outcome.
• Highlighted again importance of convective
volume (>17.4 litres, better cardiovascular and
overall mortality).
• Selection bias (patients >17.4 L have less
diabetes, higher blood flow rate, higher serum
albumin, lower serum phosphate, lower
interdialytic weight gain).

32. Turkish Results

33. Maduell et al 2013
ESHOL Trial
• OL-HDF vs high flux HD.
• Adequate number (906).
• Positive survival advantage 30 % reduction of all cause
mortality in favour of OL-HDF.
• Convective volume >18 litres.
• Survival advantage independent of middle molecule
clearance (no difference between the 2 arms).
• OL-HDF arm with less DM, less catheters, slightly
younger, low Charlson morbidity score.
• 39% discontinued treatment.

34. Spanish Study

35. Wang et al 2014
Systematic Review
• 16 Trials including 3,220 patients.
• HDF did not reduce all cause mortality or cardiac
events significantly.
• It reduced symptomatic hypotension and B2
microglobulin level.
• No impact on small molecule clearance (Kt/V).
• Increased chances to receive a kidney transplant for
HDF patients but non significant.
• Limitations: suboptimal quality trials, underpowered,
imbalance in some prognostic variables at baseline.
• Benefits of HDF vs HD for CVS outcomes and mortality
remain unproven.

36. Nistor et al 2014
Systematic Review
• 35 Trials (4,039 participants).
• Convective dialysis may reduce cardiovascular
but not all-cause mortality.
• Effects on nonfatal cardiovascular events and
hospitalization are inconclusive.
• Treatment effects of convective dialysis are
unreliable due to limitations in trial methods
and reporting.

37. Siriopol et al 2015
HDF Romanian Experience
• Retrospective analysis incident and prevalent
HDF vs HD.
• Survival benefit in both incident and prevalent
HD. (HR 0.58 and 0.24)
• Adequate number 1546 prevalent and 2447
incident patients.

38. Mercadal et al 2015
HDF French Experience
• Retrospective analysis of incident HDF vs HD.
• REIN registry HDF/HD (5526/28407) from
2008-12.
• HR of all cause and cardiovascular mortality in
HDF patients 0.84 and 0.73 respectively.

39. OL-HDF Prevalence
• Europe: 50800/294400 (as of 2010)
• Japan: 2013: 31 371/ 314 438. (Masakane et al 2015)
• USA:
– Increased 5X over 2 years.

40. Prevalence of HDF in Europe by
2010

41. Optimal Convective Volume
• DOPPS >15 l/session (retrospective
observational study).
• Contrast and Turkish trials (subgroup analysis
survival advantage > 17 & 22 l/session).
• ESHOL > 22 l/session.
• Standardizing convective volume to body
surface area correlated well with survival
(Davenport et al 2015, Peters et al 2015).

42. Convective Volume & Solute Reduction
Ratio for Each Treatment Type

43. Minimum Convection Volume
- <20% of the processed blood volume
(high flux).
- >20% of the processed blood volume
(HDF).
- Minimum is 20 litres to achieve the
desired effect.
- High flux: UF coefficient 20ml/h/mm
Hg/m2 and sieving coefficient of 0.6 B2
microglobulin.

44. Effect of Blood Flow Rate

45. Recommendation to Obtain The
Optimal HDF Dose
(Francisco Maduell 2015)

46. Post versus Pre Dilution

47. Choice of HDF versus HD

48. Reasons of Not Using HDF

49. Barriers Against HDF

50. KDOQI HD Adequacy Guideline
2015 Update
Further study is needed before HDF can be
recommended.

51. Adequacy of Renal Replacement
Therapy
Electrolyte &
Acid/base Control
Anaemia
Status
Nutritional
status
Middle molecule
clearance
Small molecule
clearance
Adequacy
Volume Control
Blood Pressure
Control
Well Being
Quality of Life
Quality of
Sleep
Long Term
Survival

52. THANK YOU