**5. Haemodiafiltration**

improvements in quality‐of‐life measures from switching to NHD [62] or SDHD [63], some show only small improvements in kidney‐specific measure of quality of life [64], while others show no difference. Larger studies have shown a reduction in depressive symptoms related

Data from the recent FHN daily trial showed a significant increase in quality‐of‐life score in the SDHD group [35] with no specific benefit from NHD over CHD at home. In the FHN NHD arm, however, both groups had an increase in their quality‐of‐life score showing the positive effect that the setting of the haemodialysis treatment has on this outcome [36] regardless of prescription. Perceived burden on unpaid carers is high among HD patients [66]; however, the FHN trials did not show a higher perceived burden with either SDHD or LDNHD [67].

The patient‐reported experience on both LDNHD and SDHD has been positive in terms of physical, psychological and lifestyle aspects [68]. There is also an associated faster recovery time with home haemodialysis [69]. Once again, it is fair to say once again that the jury is still with regard to whether these treatments truly impact on quality of life. In general, the effect

Intensive dialysis has been used very successfully in pregnancy. A case series from Canada [70] shows a markedly improved live birth rate and duration of pregnancy with a dose response between dialysis and pregnancy outcomes. Women who had >36 hours of dialysis per week had significantly improved live birth rates (85 vs. 45% in those who had <20 hours of dialysis per week), which again demonstrates and gives strength to high‐dose dialysis.

While there are many advantages of home haemodialysis, the treatment is not suitable for all patients and it is not a treatment without disadvantages. Although exceedingly rare, there is always the possibility that human error can occur resulting in significant blood loss through a variety of mechanisms. There are reports of patient deaths from exsanguination while on home haemodialysis [71]. The sophistication of safety mechanisms is continually improving to make this event less likely with blood leak detectors, pressure monitoring and line discon‐

A clear finding from the FHN trial was an increase in interventions needed for vascular access with 47% of the frequent dialysis group requiring intervention compared with 29% in the CHD group. Interventions to fistulas were required much more often than in catheters. This was not an entirely surprising finding given the considerably increased use of vascular access form more frequent haemodialysis. A solution to this could be the use of a buttonhole technique for fistula cannulation or using single‐needle haemodialysis to reduce the number of needling events. The evidence, however, is not there to support this practice and a systematic review of buttonhole cannulation in home haemodialysis patients found an increase in infectious events, an increase in staff support required and no reduction in surgical interventions compared with

seems to be positive with a paucity of data suggesting a negative impact.

**4.2. Disadvantages of more frequent and home haemodialysis**

nect detectors featuring on newer machines.

to increased dialysis frequency [65].

108 Advances in Hemodiafiltration

*4.1.7. Pregnancy*

Haemofiltration allows clearance of solutes of up to 20 kDa through the process of convection as previously described. Large volumes of replacement fluid are required for the treatment, and this can be administered either before the filter (pre‐dilution) or after the filter (post‐ dilution). Newer technology also allows a mix of pre‐ and post‐dilution or mid‐dilution in an attempt to gain the advantages of both pre‐ and post‐dilution (largely the anticoagulant requirement) [73].

Conventional HDF provides enhanced B2M clearance compared with HD [74]. It is associated with a reduction in pro‐inflammatory cytokines such as IL‐6 and TNF‐α [75] and reduced episodes of hypotension during treatment [76]. There does not appear to be a benefit in terms of left ventricular mass, pulse wave velocity or ejection fraction [77]. This could be due to achieving low substitution volumes or large interdialytic fluid shifts induced by conventional thrice‐weekly schedule.

There have been three recent large prospective clinical trials, which have compared HDF with high‐flux HD with contrasting results. The ESHOL study [78], a Spanish study, showed promising results with a 30% lower all‐cause mortality, a 33% lower cardiovascular mortality and 55% lower infection‐related mortality compared with haemodialysis. A Dutch study [79] showed no difference in outcome between HDF and HD and a Turkish [80] study drew the same conclusion. Looking back at these studies, the ESHOL study achieved the highest convective volumes (22.9–23.9 l per session) and *post hoc* analyses of the Turkish and Dutch study also show an association between high convection volume and a survival benefit.

In order to provide HDF with high convection volumes, large volumes of sterile replacement fluid are required (>15 l), which would not be practical with pre‐packaged solutions. Instead of online preparation of fluid, which is the most practical solution, HDF uses an additional 50– 80 l of water per session [81] (with a typical haemodialysis session using around 500 l of mains water to generate dialysate [82]). Ultrapure dialysate must be generated by the machine to the standards previously described.

#### **5.1. Adding HDF in the home setting**

There appears to be a benefit from high convective volume haemodiafiltration. The biggest determinants to achieving a high convective volume are treatment time and blood flow [83]. A blood flow between 360 and 500 ml/min is required to achieve the necessary transmembrane pressure [84]. A well‐functioning vascular access would therefore also be required. Although there are reports of achieving a convective volume of >20 l with a haemodialysis catheter, a well‐functioning AV fistula would allow higher blood flows [84].

Given that treatment time is clearly an important factor in achieving the dose of HDF associated with improved outcomes, the home setting is an ideal place to deliver the treatment. Vascular access would not be a barrier and combining frequent haemodialysis with a convective treatment should maximize middle molecule clearance. Switching patients from a conven‐ tional HDF schedule to a short daily schedule has been reported to result in a higher removal of middle and large molecules, a reduction in phosphate binders, the disappearance of post‐ dialysis fatigue, an improvement in nutritional status as well as a 30% reduction in left ventricular mass [85]. The improvements in switching to more frequent OL‐HDF are outlined in **Table 1**.


a: *P*<0.05;

b: *P*<0.01 with respect to baseline value.

Adapted from Maduell et al. [85].

Abbreviations: URR, urea reduction ratio; sp*K*<sup>t</sup> /*V*, single‐pool *K*<sup>t</sup> /*V*; e*K*<sup>t</sup> /*V*, equilibrated *K*<sup>t</sup> /*V*; std*K*<sup>t</sup> /*V*, standard *K*<sup>t</sup> /*V*; TAC, time average concentration; TAD, time average deviation; ERK, equivalent renal urea clearance.

**Table 1.** Change from three times a week on‐line haemodiafiltration (OL‐HDF) to short daily on‐line haemodiafiltration (D‐OL‐HDF): comparison of urea kinetics during the two study periods.

While the technology to provide HDF in the home setting exists, it is not widely used at present and there is very little published literature about HDF as a home therapy. Until recently, there have not been haemodialysis machines specifically manufactured for the home market. As a result, patients have been trained on the machines used in the main dialysis unit. Using the same technology both in the home and in the main dialysis unit makes the logistics of maintenance much easier. The health care team, including the technicians, are often more comfortable and experienced using and providing support for a single machine. As technology has developed and haemodialysis machines have become more advanced, it is important that more user‐friendly technology, specifically for the home market, is developed. This will allow further uptake and expansion of home dialysis programmes.

A blood flow between 360 and 500 ml/min is required to achieve the necessary transmembrane pressure [84]. A well‐functioning vascular access would therefore also be required. Although there are reports of achieving a convective volume of >20 l with a haemodialysis catheter, a

Given that treatment time is clearly an important factor in achieving the dose of HDF associated with improved outcomes, the home setting is an ideal place to deliver the treatment. Vascular access would not be a barrier and combining frequent haemodialysis with a convective treatment should maximize middle molecule clearance. Switching patients from a conven‐ tional HDF schedule to a short daily schedule has been reported to result in a higher removal of middle and large molecules, a reduction in phosphate binders, the disappearance of post‐ dialysis fatigue, an improvement in nutritional status as well as a 30% reduction in left ventricular mass [85]. The improvements in switching to more frequent OL‐HDF are outlined

/*V* 2.30 ± 0.20 1.13 ± 0.15<sup>b</sup> 1.11 ± 0.11<sup>b</sup>

/*V* 1.96 ± 0.17 0.90 ± 0.12<sup>b</sup> 0.88 ± 0.08<sup>b</sup> URR *%* 84.3 ± 2.5 64.2 ± 5.3<sup>b</sup> 63.3 ± 4.2<sup>b</sup>

EKR *mL*/*min* 19.2 ± 0.5 24.2 ± 2.6<sup>b</sup> 23.8 ± 1.9<sup>b</sup>

/*V* 2.62 ± 0.1 3.87 ± 0.3<sup>b</sup> 3.86 ± 0.2<sup>b</sup> Weekly URR *%* 253 ± 7.5 385 ± 32<sup>b</sup> 380 ± 25<sup>b</sup>

/*V*, single‐pool *K*<sup>t</sup>

While the technology to provide HDF in the home setting exists, it is not widely used at present and there is very little published literature about HDF as a home therapy. Until recently, there have not been haemodialysis machines specifically manufactured for the home market. As a result, patients have been trained on the machines used in the main dialysis unit. Using the same technology both in the home and in the main dialysis unit makes the logistics of maintenance much easier. The health care team, including the technicians, are often more comfortable and experienced using and providing support for a single machine. As technology has developed and haemodialysis machines have become more advanced, it is important that

time average concentration; TAD, time average deviation; ERK, equivalent renal urea clearance.

**Table 1.** Change from three times a week on‐line haemodiafiltration (OL‐HDF) to short daily on‐line haemodiafiltration (D‐OL‐HDF): comparison of urea kinetics during the two study periods.

/*V*; e*K*<sup>t</sup>

/*V*, equilibrated *K*<sup>t</sup>

/*V*; std*K*<sup>t</sup>

/*V*, standard *K*<sup>t</sup>

/*V*; TAC,

/*V* 6.90 ± 0.59 6.78 ± 0.91 6.67 ± 0.64

/*V* 5.88 ± 0.52 5.39 ± 0.75<sup>a</sup> 5.30 ± 0.50<sup>a</sup>

**Baseline Month 3 Month 6**

well‐functioning AV fistula would allow higher blood flows [84].

in **Table 1**.

110 Advances in Hemodiafiltration

Weekly sp*K*<sup>t</sup>

Weekly e*K*<sup>t</sup>

std*K*<sup>t</sup>

a: *P*<0.05;

b: *P*<0.01 with respect to baseline value. Adapted from Maduell et al. [85].

Abbreviations: URR, urea reduction ratio; sp*K*<sup>t</sup>

sp*K*<sup>t</sup>

e*K*<sup>t</sup>

The ideal home HD machine has been described [86] as one which is fast and easy to setup, allows a range of prescriptions (such as short daily and nocturnal), teaches and interacts with the patient and allows the patient to deliver intravenous fluid at the push of a button. The description suggests the ability of the machine to re‐use blood sets and dialysers, prepare all fluids to a standard beyond ultrapure and have the ability to provide HDF. There are many machines in development and it is likely that this "ideal machine" will be in existence in the near future. There is the potential for HDF machines to be complex given the choice in pre‐ dilution, post‐dilution and mixed dilution and the blood and dialysate flow. Technology should strike a balance, remaining simple for safe use with minimal margin for error and fast training times but also allow some flexibility to tailor treatment.

As previously described, providing a high water quality is of great importance given the high volume that is infused into the patient. The body of evidence to support the use of ultrapure water really lies in convective treatments, and thus, an essential requirement for any home HDF programme will be the production of ultrapure dialysate. Water may contain both chemical and microbiological contaminants, and in the home setting, this is likely to vary considerably depending on the local feed water. A variety of contaminants can have clinical consequences, such as chloramines, leading to haemolytic anaemia [87], calcium and magne‐ sium contributing to a "hard water syndrome" [88] and nitrates [89], zinc [90] and fluorides [91] have all been documented to have potential clinical effects. After initial assessment of the feed water and the subsequent installation of the filters and water softeners, a surveillance programme for chemical contaminants, endotoxins and bacteria is important. This logistics of such a programme needs to be considered as the sampling protocol, laboratory protocols and the transport and storage of samples must all be carefully planned.

Microbiological contamination can still theoretically occur. Reverse osmosis units filter out substances with a molecular weight > 200 kDa and thus bacterial fragments and small endotoxins can still pass through [92]. Vigilance must be employed for unexplained febrile episodes or signs of chronic inflammation. This would apply to both home haemodialysis and haemodiafiltration.

Portability is an important factor for dialysis patients. Peritoneal dialysis has provided a treatment that can be carried out virtually anywhere making the treatment appealing for patients who work or need to travel. To date, the quantity of water and the size of the water treatment devices has limited the portability of haemodialysis. Increasingly, there are haemo‐ dialysis machines that allow portability by utilizing sorbent technology to purify water and thus reduce water requirements [93]. With the high convective volumes required for adequate HDF, water requirements remain high and thus limit portability. Developments in this area are needed allow to make HDF a more appealing home treatment for patients. Water use must be minimized and where possible, water should be recycled. Water rejected from reverse osmosis units can be recycled and used elsewhere in the home or dialysis unit and this is being increasingly utilized [82].

Anticoagulation must be a major consideration for any extracorporeal dialysis therapy. Many patients on home haemodialysis manage well with the administration anticoagulation, and unfractionated heparin and low molecular weight heparin are in common use. These strategies can also be used in HDF and should not pose a barrier to home HDF use. HDF may allow dialysis without anticoagulation through the use of pre‐dilution HDF. This may be particularly helpful in patients with prolonged bleeding or intolerances to anticoagulation.

Today's dialysis technology enables HDF to be delivered in the home setting safely with the production of ultra‐pure dialysate and detection of venous dislodgement. There is a growing experience of centres using this technology [94] with a positive experience. Further details on optimal heparinization regimes, water quality variability and its surveillance in home HDF are necessary to define best clinical practice. It is likely that new technology coupled with increasing HDF uptake in dialysis centres will lead on to increasing use of HDF at home.

#### **5.2. Economic impact of HD and HDF**

Haemodialysis treatment in general is very costly, and in the United Kingdom, 1–2% of the National Health Service budget is spent on renal care with only 0.05% with ESRF [95]. After consumables, a large proportion of the cost is made up of direct nursing care and transportation [96] (both of which are considerably less in home haemodialysis). Home haemodialysis has been estimated to cost over a third less than hospital‐based haemodialysis in the United Kingdom [96] and frequent home haemodialysis has been shown to offer a cost saving in both Canada and Australia too [97].

In addition to the reduced transport and nursing costs, savings are also offered from a reduction in hospital admissions [37] and a reduction in medication costs (particularly phosphate binders) [98].

The initial setup costs of home haemodialysis are high due to the cost of training, the equipment and installation. These initial costs are usually paid back by 14 months after which savings occur [99], making home haemodialysis an attractive option not only from the clinical benefits but also from the cost‐saving aspect.

Costs of high‐flux dialysers have also reduced considerably over time and high‐flux haemo‐ dialysis is now the common standard care. A UK Study looked at the costs of 34 patients switching to OL‐HDF and 44 who remained on high‐flux HD. The cost of the treatment was either more expensive or cheaper depending on the choice of blood lines. There was a cost saving in the OL‐HDF group in terms of phosphate binders. Lebourg et al. [81] looked at >28,000 dialysis treatments in a single centre and once again HDF was found to be either cheaper or more costly (-€1.29 to +€4.58 per session) depending on treatment variables selected. It is clear that from a cost perspective, there is little difference between HDF and high‐flux HD.
