Online Hemodiafiltration

Although the physical and chemical concepts of diffusion and convection are well known, dialysis has been carried out mainly by diffusion during its first four decades. This form of dialysis, hemodialysis (HD), has ensured the survival of millions of patients with advanced kidney disease worldwide and has met the increasing needs generated in the 50 years since dialysis was considered for long-term renal replacement therapy.

The delay in incorporating convection techniques as routine treatment has technological and economic reasons. Hemofiltration (HF) or hemodiafiltration (HDF) modalities require the use of dialyzers of high permeability and, at the same time, monitors with volume control and a dual pump. Replacement fluid is a further cost, is the main reason for abandoning HF, and was a key constraint on the initial HDF technique, with volumes ranging between 3 and 10 L. In the 1990s, the introduction of online HDF techniques using the dialysis fluid itself as a replacement solution has meant a revolution in HD units. It has taken another 10 years to renovate and upgrade water treatment, introduce specific monitors, and incorporate safety filters to ensure ultrapure dialysate.

What is hemodiafiltration?

The European Dialysis working group (EUDIAL) revisited the definition of hemodiafiltration (1) as the blood clearance treatment that combines diffusive and convective transport using a high-flux dialyzer with an ultrafiltration coefficient (KUF) >20 mL/mm Hg/h/m2, a sieving coefficient for ß2-microglobulin >0.6, and a percentage of effective convective transport greater than 20 percent of the total processed blood. Convection volume was defined as the sum of the replacement volume and the intradialytic weight loss achieved.

Can I provide online hemodiafiltration?

To answer this question, complete the checklist in Table 1. If the answer to all of the questions is yes, you are able to provide this treatment modality. If the answer to one or more of the questions is no, the treatment cannot be started until each point has been resolved. This checklist does not include training, because the current technology has been greatly simplified and is easy to use.

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Why should we systematically implement online hemodiafiltration?

Online HDF (OL-HDF) can be indicated for all patients receiving hemodialysis, because there are no contraindications. Online HDF techniques constitute progress toward renal replacement therapy that is most similar to the native kidney. These techniques offer a higher clearance of uremic substances with a greater range of molecular size.

The possible clinical benefits that convection techniques can provide are better control of hyperphosphatemia, malnutrition, inflammation, anemia, infectious complications, joint pain, amyloidosis associated with dialysis, intradialytic tolerance, insomnia, irritability, restless leg syndrome, polyneuropathy, and itching.

Does online hemodiafiltration improve survival?

Observational studies, adjusted for demographic and comorbidity factors, have shown that a lower risk of death is associated with online HDF (25). In addition, three large prospective randomized clinical trials (RCTs) have been conducted to compare survival outcomes in prevalent patients. The CONTRAST study randomized 714 patients to low-flux HD or OL HDF and at the end of the study the two groups showed no difference in survival (6). Similarly, in the Turkish HDF study, 782 patients were randomized to HF HD or OL HDF and the outcome was not affected by treatment allocation (7). However, the ESHOL study randomized 906 patients to HF-HD or OL HDF, and the allocation to OL HDF was associated with a 30 percent reduction in all-cause mortality (8).

Recently, two meta-analyses, including the three RCTs mentioned above, have confirmed that OL-HDF increases overall and cardiovascular survival. Online HDF was associated with a reduction of 13 percent to 16 percent in all-cause mortality and 25 percent to 27 percent in cardiovascular mortality (910).

Association between survival and convective volume

In all large RCTs, the connvective volume seemed to be an important issue. A post hoc analysis of the CONTRAST study showed that in the group of patients with the highest delivered convection volume (upper tertile >21.95 L), mortality was 39 percent lower than in patients randomized to LF-HD (6). In a Turkish study, the median value of substitution volume in the OL-HDF group was 17.4 L, and when patients were stratified according to this threshold, those in the high-efficiency OL-HDF group were associated with a 46 percent risk reduction for overall mortality and a 69 percent risk reduction for cardiovascular mortality (7). In post hoc analyses of the ESHOL study, mortality in the intermediate tertile (23.1–25.4 L per session) and upper tertile (>25.4 L) was significantly lower than that in patients randomized to HD: 40 percent and 45 percent risk reduction for overall mortality, respectively (8).

Convective dose prescription

Convective target volume should therefore be the maximum possible for the individual characteristics and parameters of each patient dialysis. Based on the results of secondary analyses of the main clinical trials, the current recommendation of the optimal dose of OL-HDF, in postdilutional mode with a thrice-weekly treatment schedule, would be a convective volume >23 L per session. However, bear in mind that this recommendation is based in secondary analysis, and therefore there could be a selection bias. Patients receiving greater convective volume are those in better overall condition, with good vascular access and less diabetes or cardiovascular disease. In the absence of more conclusive scientific evidence, it seems a reasonable and affordable recommendation that should be confirmed with future clinical trials.

How to optimize online hemodiafiltration

Vascular access

A native fistula is the best option for all HD modalities as well as for OL-HDF. However, the use of a native fistula or graft has decreased because of greater patient age and the increased prevalence of cardiovascular disease and diabetes. The use of a catheter means a lower blood flow (Qb) and convective volume. In a multicenter study, only a third of the patients with catheters achieved a minimum of 21 L of replacement volume target (11). It’s important to consider that patients with catheters should increase the duration of dialysis to achieve an adequate dialysis dose (additional 30 minutes if the catheter is used in the normal position and 1 hour if it is in a reversed position) (12). Therefore, catheter use should not be seen as an obstacle for HDF, but increasing dialysis duration must be considered.

Blood flow

The main limiting factor for convective volume is Qb. In postdilution mode, the maximum recommended infusion flow is 33 percent of the Qb value. Achieving adequate convective volumes may be complicated in patients with limited Qb. Some authors have suggested that the prescription of Qb is more a matter of treatment policy in each dialysis unit than the characteristics of the patients themselves (13).

Dialysis machine

New dialysis machines that allow an automatic infusion flow (Qi) to maximize the convective volume have reduced the risk of hemoconcentration and have increased convective volume (1415).

Dialyzer

Online HDF needs high-flux dialyzers. Currently, dialyzers are available with large convective capacity, with KUF between 40 and 100 mL/h/mm Hg. This means that with a transmembrane pressure of 200 mm Hg, allowing Qi of 133 to 333 mL/min, Qi is much higher than those that can actually be used. Therefore, a dialyzer with KUF > 45 mL/h/mm Hg is not a limiting factor in the convective volume, and the differences obtained in the purification capacity would be minimal.

Dialysis duration

Increase in the duration of dialysis will always be a valid alternative to increase in convective volume.

Is it time to change from diffusion techniques to online hemodiafiltration?

We are fully convinced that now is the time to change to convective techniques. First, the available scientific evidence supports that this treatment increases overall and cardiovascular survival. Second, technological development in water treatment, advances in monitors, and the widespread use of synthetic high-flux dialyzers, make this a feasible proposition. Finally, online HDF provides possible clinical benefits, and we have found no published literature showing any undesirable effects.

References

1. 

Tattersall JE, et al. Online haemodiafiltration: definition, dose quantification and safety revisited. Nephrol Dial Transplant 2013; 28:542–550.

2. 

Canaud B, et al. Mortality risk for patients receiving hemodiafiltration versus hemodialysis: European results from the DOPPS. Kidney Int 2006; 69:2087–2093.

3. 

Jirka T, et al. Mortality risk for patients receiving hemodiafiltration versus hemodialysis. Kidney Int 2006; 70:1524–1525.

4. 

Panichi V, et al. Chronic inflammation and mortality in haemodialysis: effect of different replacement therapies. Results from the RISCAVID study. Nephrol Dial Transplant 2008; 23:2337–2343.

5. 

Vilar E, et al. Long-term outcomes in online hemodiafiltration and high flux hemodialysis: a comparative analysis. Clin J Am Soc Nephrol 2009; 4:1944–1953.

6. 

Grooteman MP, et al. Effect of online hemodiafiltration on all-cause mortality and cardiovascular outcomes. J Am Soc Nephrol 2012; 23:1087–1096.

7. 

Ok E, et al. Mortality and cardiovascular events in online-hemodiafiltration (OL-HDF) compared with high-flux dialysis: results from the Turkish Online Haemodiafiltration Study. Nephrol Dial Transplant 2013; 28:192–202.

8. 

Maduell F, et al. High-efficiency postdilution online hemodiafiltration reduces all-cause mortality in hemodialysis patients. J Am Soc Nephrol 2013; 24:487–497.

9. 

Nistor I, et al. Convective versus diffusive dialysis therapies for chronic kidney failure: an updated systematic review of randomized controlled trials. Am J Kidney Dis 2014; 63:954–967.

10. 

Mostovaya I, et al. Clinical evidence on hemodiafiltration: a systematic review and a meta-analysis. Semin Dial 2014; 27:119–127.

11. 

Marcelli D, et al. High-volume postdilution hemodiafiltration is a feasible option in routine clinical practice. Artif Organs 2015; 39:142–149.

12. 

Maduell F, et al. How much should dialysis time be increased when catheters are used? Nefrologia 2008; 28:633–636.

13. 

Chapdelaine I, et al. Treatment policy rather than patient characteristics determines convection volume in online post-dilution hemodiafiltration. Blood Purif 2014; 37:229–237.

14. 

Panichi V, et al. Divert to ULTRA: differences in infused volumes and clearance in two on-line hemodiafiltration treatments. Int J Artif Organs 2012; 35:435–443.

15. 

Maduell F, et al. Impact of the 5008 monitor software update on total convective volume. Nefrologia 2014; 34:599–604.