**4. HDF prescription and implementation of best practices**

#### **4.1. Current status**

Online HDF can no longer be considered an experimental treatment but has now developed into a mature and accepted RRT. In fact, this dialysis modality is employed for sustaining the lives of more than 160,000 ESKD patients worldwide, including 80,000 in Europe, Middle East, and Africa. Europe played a leading role in developing this therapy, where the prevalence of HDF is close to 18% (varying across countries from 0 to 100%). The annual growth rate is approximately 6% [30]. In 2013, Japan treated 31,273 patients with HDF (23,445 thereof on online HDF), representing 10% of its total dialysis population (294,605 patients; Kawanishi, personal data). The number increased by 4% between 2013 and 2014 as positively influenced by the implementation of a specific reimbursement fee in 2012. Interestingly, in Japan, the predominant HDF mode is predilution HDF (90.8% of HDF treatments).

#### **4.2. Treatment schedule prescription**

The prescription of the HDF treatment schedule is based on the usual target of providing optimal RRT to the ESKD patient. It is a composite and trade‐off between patient‐specific issues (e.g., metabolic needs, treatment tolerance and acceptance, and patient‐treatment interaction), local logistical and practical issues (e.g., facility and/or modality availability), and health regulation and reimbursement policies.

for each patient per hour. Consequently, it could be possible to increase the time of the shift and the treatment time in a cost‐neutral manner. Is this possible? According to Tsobanelis et al. [27], new dialysis equipment under testing in HDF mode for fistula patients had a 24% reduction in the number of major handling steps compared to the previous dialysis machine

Other aspects to be considered when targeting an increase of patient to nurse ratio are those related to safety. The risk of harm has to be reduced as much as possible, and one option is to reduce this risk by the improved design of the equipment. As an example, we can again mention the recent experience of Tsobanelis et al. [28], who reported that the tested new equipment had 27% fewer major process steps and touch points critical to hygiene compared to the current machine version. The authors found it particularly noteworthy that it was possible to avoid disconnection of the arterial line from the arterial needle with the redesigned

Finally, in the time of green economy, the authors also highlighted that the switch from an infusion line to an integrated infusion port reduced the volume of contaminated waste. The major source of waste relates to the disposables (bloodlines and dialyzers), so that newly designed, integrated disposables can facilitate a reduction of disposable waste, for example, of approximately 0.2 kg/session as reported by Schleser et al. [29], which, given an average of 10,000 treatments yearly delivered by a dialysis unit, translates into 2000 kg less waste. In terms of carbon footprint, one should also consider the consumption of water and energy and how this can be limited, for example, by having a more efficient water

Online HDF can no longer be considered an experimental treatment but has now developed into a mature and accepted RRT. In fact, this dialysis modality is employed for sustaining the lives of more than 160,000 ESKD patients worldwide, including 80,000 in Europe, Middle East, and Africa. Europe played a leading role in developing this therapy, where the prevalence of HDF is close to 18% (varying across countries from 0 to 100%). The annual growth rate is approximately 6% [30]. In 2013, Japan treated 31,273 patients with HDF (23,445 thereof on online HDF), representing 10% of its total dialysis population (294,605 patients; Kawanishi, personal data). The number increased by 4% between 2013 and 2014 as positively influenced by the implementation of a specific reimbursement fee in 2012. Interestingly, in Japan, the

The prescription of the HDF treatment schedule is based on the usual target of providing optimal RRT to the ESKD patient. It is a composite and trade‐off between patient‐specific issues

**4. HDF prescription and implementation of best practices**

predominant HDF mode is predilution HDF (90.8% of HDF treatments).

from the same company.

84 Advances in Hemodiafiltration

treatment system.

**4.1. Current status**

**4.2. Treatment schedule prescription**

process of blood reinfusion at the end of the session.

The duration and frequency of sessions are based on two main components: (1) patient's metabolic needs and dialysis adequacy targets and (2) extracellular fluid management and cardiovascular tolerance depending on ultrafiltration rate. Increasing session length and frequency will facilitate the achievement of a high ultrafiltration volume. A pragmatic approach is to estimate a suitable convective dose for a given patient and to increase the treatment time according to the limitations present regarding effective blood flow or other hemorheological factors.

In clinical practice, prescription comprises the setting of the substitution rate (substitution volume per session extended to weekly volume) and adding the required weight loss to achieve the dry weight for that patient. Based on the results of recent studies, a minimal substitution volume of 60 L/week (or 40 L/m2 body surface area) is required in individual ESKD patients to improve patient outcome. The additional ultrafiltration volume required for the correction of extracellular fluid volume excess has to be added to the substitution volume.

The hemodialyzer used for HDF must contain membranes that are highly permeable for both water (Kuf>50 mL/h/mmHg) and solutes (sieving coefficient for β2M≥0.6) with adequate dialyzer surface area. Filter design should favor a low internal blood flow resistance, thereby reducing membrane fouling and minimizing backfiltration as much as possible. A simple rule of thumb commonly applied in clinical practice is to consider 1 m2 /each 200 mL/min effective extracorporeal blood flow, meaning that a 2.0 m2 hemodialyzer is appropriate for a blood flow of 400 mL/min [31].

In the past, the composition of the dialysis fluid differed from that of the substitution fluid. This is not the case in online HDF. Given the current definition of convective treatment adequacy, based on 23 L/session of convective dose in postdilution HDF, this equality of fluid compositions, and also the HDF mode, may affect the mass balance of electrolytes during the treatment session. Several studies dealing with the dialysate/substitution fluid prescription and focusing on sodium, calcium, and bicarbonate have been published.

Sodium: The importance of the correct sodium balancing during dialysis, preventing sodium overload with resultant thirst and water overload, has long been recognized. This risk of sodium loading also has to be considered in high efficiency treatments coupling diffusion and high volume convection. In a 1991 evaluation of HDF sessions with convective doses ranging between 9.1 and 16.7 L/week, Pedrini et al. [32] found that sodium balance was mainly affected by the sodium concentration gradient between initial plasma water and dialysate, the sodium level in the substitution fluid, and the imposed ultrafiltration rate. In the same patients treated with similar operating conditions, significantly lower net sodium removal was observed when on predilution compared to postdilution HDF [33]. Despite the complexity of managing the multifactorial equations describing the relationship between affecting variables and sodium balance (e.g., the laboratory method for the determination of sodium and the negative charge of plasma proteins) [33], ideal modern equipment should be able to automatically address sodium balance.

Calcium: The target in the case of calcium is to maintain a neutral calcium balance, as an excessive calcium load has been associated with vascular calcification, whereas calcium depletion has been linked to worsening secondary hyperparathyroidism and decreased bone mass [34]. Here also, the modality of HDF affects the balance. Although calcium balance during postdilution online HDF does not differ from standard HD, it is usually recommended to increase the dialysate/substitution fluid calcium concentration by 0.25 mmol/L in predilution HDF mode in order [34]. In addition, discrepancies between expected and observed concen‐ trations in the dialysate/substitution fluid play an important role in the case of online HDF. In a volumetric system based on conductivity, the sodium for the bicarbonate dialysate/substi‐ tution fluid comes in part from a basic component and in part from an acidic component. In cases of a decrease in dialysate sodium with concomitant increase of bicarbonate, a lower proportion of the acid component will produce a lower than expected calcium level in the dialysate/substitution fluid [35].

Bicarbonate: a positive bicarbonate balance is targeted during the treatment session to neutralize the interdialytic accumulation of strong acid anions and to avoid starting the next session with metabolic acidosis. However, there is also a risk of postdialysis alkalosis. In a recent publication by Havlin et al. [36] analyzing 68 patients on postdilution HDF treated for 4 to 5 h with 80 to 90 mL/min of substitution fluid (19–27 L/session) with a dialysate bicarbonate concentration of 32 mmol/L, 34% of patients were acidotic at dialysis initiation, but 80% had metabolic alkalosis after dialysis. They speculated that this was due to an excessive elimination of retained and endogenous anions. According to the authors, this observation requires further investigation. In any case, several factors affect the mass balance. A significantly lower bicarbonate gain was observed in predilution HDF versus postdilution HDF [37]. As is true for all electrolytes, the difference in concentration between bicarbonate levels in the dialysate/ substitution fluid and in the blood at the initiation of the session is positively correlated to the mass transfer. Therefore, to maintain the same bicarbonate balance when moving from postdilution HDF to predilution HDF, dialysate bicarbonate concentration should be increased by 2 mmol/L. In fact, in predilution HDF, bicarbonate levels of the blood entering in the dialyzer increase, enhancing the loss across the membrane and reducing the normal gain by diffusion from dialysis fluid to blood [33].
