**5. Hemodiafiltration in a nutshell**

1-year hospitalization days (*p* = 0.07). However, the 1-year mortality was found to be 33% in the pUF group and 23% in the control cohort, although this result was not statistically significant. In comparison to standard medical treatment, pUF was found to significantly improve volume overload (*p* < 0.05), the NYHA functional class (*p* < 0.001), and mental health (*p* < 0.05) of the patients. Furthermore, in the pUF group, the hospitalization days for all causes, including cardiovascular incidents, were significantly reduced during the interim periods (*p*

Another study evaluated pUF in patients with severe HF that was refractory to aggressive drug therapy [42]. Treatment with pUF was considered in these patients, as they had been hospitalized at least three times in the preceding year for ADHF that had required extracor‐ poreal UF. This study comprised 48 patients; of those, 30 received one nocturnal icodextrin exchange, 5 received two daily exchanges, and the remaining 13 received two to four sessions per week of automated peritoneal dialysis (PD). In the first year of therapy, renal function remained stable with a decline in pulmonary artery systolic pressure to 40 ± 6.09 mmHg from 45.5 ± 9.18 mmHg (*p* = 0.03). At the same time, significant improvement was noted in the NYHA functional status. Furthermore, patient hospitalizations decreased to 11 ± 17 days/patient-year from 43 ± 33 days/patient-year seen in the preceding year, which was before the onset of PUF treatment (*p* < 0.001). Thus, this study confirms the efficacy of PUF treatment in elderly patients

Recently, a systematic review conducted to evaluate the efficacy of PD in patients with refractory CHF identified 21 studies from 13 countries [43]. This review comprised 673 patients and suggested that in patients with refractory CHF, PD can be an effective and safe treatment option, leading to improved heart function and weight control. It also reported that PD can reduce patient hospitalization days without any progressive worsening of renal function. The

Sustained low-efficiency dialysis (SLED), or sustained low-efficiency daily dialysis (SLEDD), is a conventional hemodialysis that is performed over a longer period (6–12 h) of time using lower rates of blood flow (50–200 mL/min) and dialysate flow (200–400 mL/min). It is an alternative treatment in critically ill patients with affected kidney function [44–46], where fluid is removed slowly over longer time ensuring better hemodynamic stability [47]. This is in particular the case when the cost of HF/HDF is considered expensive. It combines the logistic advantages, the cost-effectiveness and the scheduling flexibility of the intermittent dialysis, and the hemodynamic stability of continuous renal replacement therapy with fewer side effects during the fluid removal [48]. There is still a limited clinical data in the literature on the effectiveness of SLED in patients with CHF. However, Iorio et al.'s experience suggested that SLED is an alternative treatment for acute dialysis in patients with diuretic resistant systolic CHF [49]. Violi et al. mentioned that the SLED as an alternative treatment is the most indicated

rates of PD complications such as peritonitis were also found to be acceptable.

**4. Sustained low-efficiency dialysis (SLED) in patients with CHF**

< 0.05 and *p* < 0.001, respectively).

62 Advances in Hemodiafiltration

with chronic HF.

in NYHA class IV CHF [50].

Dialysis refers to diffusive clearance. During dialysis, low-molecular weight solutes such as sodium and potassium move down their concentration gradient. The solute must be of appropriate size to pass through a semi-permeable membrane. By passing fluid across the membrane countercurrent to blood flow, equilibration of plasma and dialysate solute concen‐ trations occur. This process may remove or add solute to the plasma water space depending upon the relative concentrations in dialysate and plasma. At the same time, water will also move along a gradient, in this case the osmolar or osmotic gradient, in effect "following" the solute. Diffusive clearance is more effective at removal of small solute, such as serum ions and urea, than for larger solutes.

Hemofiltration (HF) or ultrafiltration (UF) refers to convective clearance. The difference from dialysis is that pressure gradient rather than concentration gradient has its main effect on water movement. Solute movement is secondary and in conjunction with water. The transmembrane pressure difference can be adjusted as needed to remove water from the body down a pressure gradient. The flow of plasma water "drags" solute with it in the formation of ultrafiltrate. UF or HF is far superior for fluid clearance than diffusive clearance, and small solute clearance is almost identical. Slow continuous ultrafiltration (SCUF) is a term used for removing isotonic plasma water, which is indicated in patients with fluid overload such as those with CHF.

**Figure 1.** Principle of hemodiafiltration.

Hemodiaflitraion refers to a combination of convective and diffusive therapies. An example is the use of continuous venovenous hemodiafiltration (CVVHDF) in critically ill patients. It constitutes lower blood flow rate and slower fluid removal which may cause less hemody‐ namic instability in a hypotensive critically ill patient [51].

The setup for HDF requires a double-lumen central venous catheter, a peristaltic pump, and a filter inserted into a venovenous extracorporeal circuit [52] (**Figure 1**). Negative pressure generated by the pump allows blood circulation in the circuit, starting from the central vein and returning to the patient through the filter. Pore fibers of the filter keep water and small particles separated from blood through convective transport. Plasma water flow makes the blood concentration transient, eventually causing intravascular refilling while transferring liquids from the outer to the inner vascular space, thus safeguarding the circulating volume.

After the dispatched intravascular fluid is replaced by extravascular fluid refilling, hypovo‐ lemia can be prevented, thus preventing hemodynamic worsening. According to previous reported studies, fluid removal through HDF has affirmative hemodynamic effects. A study was done on 24 patients with resistant CHF undergoing UF; blood gas analysis (in both systemic and pulmonary arteries), plasma volume changes, and plasma refilling rate were measured after every liter of plasma water removed; UF was performed safely without side effects or hemodynamic instability; and mean right atrial, pulmonary artery and wedge pressures progressively reduced during the procedure [18]. Heart rate and systemic vascular resistance did not increase, and other peripheral biochemical parameters did not worsen during UF. Cardiac output increased at the end of the procedure and, to a greater extent, 24 h later, in relation to the increase of stroke volume. Intravascular volume remained stable throughout the entire duration of the procedure, indicating that a proportional volume of fluid was refilled from the congested parenchyma. Thus, UF is associated with hemodynamic improvement. Fluid refilling from the over-hydrated interstitium is the major compensatory mechanism for intravascular fluid removal, and hypotension does not occur when plasma refilling rate is adequate to prevent hypovolemia.

When a patient in decompensated heart failure is treated with HDF, it is important to ensure that the amount of removed intravascular water is below the amount of the capillary refilling rate; otherwise, neurohumoral activation can lead the patient to hypotension and abnormal renal function [18]. Thus, the distinctive feature of HDF is its effectiveness in removing extravascular fluids without increasing or decreasing the circulating volume and in turn avoiding neurohormonal activation and its consequences [52]. Respiratory symptoms such as dyspnea and orthopnea can be improved not only by total fluid removal but also by improve‐ ment in lung mechanics, pulmonary gas exchange, interstitial edema, vascular congestion, etc. [53, 54]. The two strategies (mechanical and pharmacological) of fluid withdrawal can have different effects on intravascular volume, hemodynamics, neurohumoral activity, and other regulatory mechanisms, leading to differing clinical outcomes. The tonicity of the fluid removed by the two strategies is different (isotonic with ultrafiltration [UF] and hypotonic with loop diuretics) [52, 55, 56]. With HDF, intravascular volume can be preserved, whereas it can be reduced with loop diuretics. After HDF, a better water-salt balance can be achieved and maintained in the body, whereas rapid worsening of this balance to the baseline abnormal state can occur with loop diuretics. A number of pathophysiology-oriented studies have documented these concepts [18, 53, 57]. Still, some ambiguity remains regarding the exact mechanisms of HDF in treating CRS and diuretic resistance.
