**1. Introduction**

Untreated end-stage renal disease (ESRD) carries a high mortality. The management of ESRD is either by dialysis or by a kidney transplant. Due to insufficient number of kidney donors in comparison with the progressive increase in the number of ESRD patients in need for dialysis,

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dialysis remains the main modality of treatment. Since the care of patients with ESRD is resource intense, it is necessary to adopt measures that render the delivery of dialysis more cost-effective and improve the quality of care. The uremic syndrome is characterized by the accumulation of uremic toxins due to inadequate kidney function. The European Uremic Toxin Work Group has listed more than 90 compounds considered to be uremic toxins. Among them, 68 have a molecular weight less than 500 Da, 10 have between 500 and 12,000 Da, and 12 exceed 12,000 Da [1]. Solutes weighing less than 500 Da are considered low molecular weight solutes and they are removed by passive diffusion down a favorable concentration gradient. Urea is considered a marker of such toxins. Its clearance, as measured by Kt/V urea, correlates with patient morbidity showing the evidence that such toxins contribute to the uremic syndrome [2]. The mortality rate of patient on maintenance dialysis has been found to be 15–20% [3]. This is despite improvements in patient care and technology. In order to increase survival in dialysis patients, it was postulated in 1983 that increasing the Kt/V in conventional dialysis may help to reduce mortality. However, the hemodialysis (HEMO) study failed to show a positive effect on patient survival when dialysis dose per hemodialysis session was in‐ creased above the current K/DOQI recommendations [4]. Possible explanation for this unfavorable outcome could be in the kinetics of urea removal which is representative of small solutes, but not of larger-sized molecules such as middle molecules, large molecular weight proteins or protein-bound solutes, thereby making Kt/V misleading [5]. Clearance of urea accounts for only one-sixth of physiological clearance [1]. In addition, several shortcomings are associated with short dialysis schedules that are not captured by Kt/V index such as extracellular fluid volume control, phosphate control, and adequate removal of middle and larger uremic molecules compounds. Beta-2 microglobulin levels are associated with the development of dialysis-related amyloidosis and possibly reduced survival [6]. It seems likely that beta-2 microglobulin is a marker for overall-middle molecule clearance, including more toxic and yet unidentified uremic compounds [7–10]. Those solutes are better removed by high-flux membranes due to their more porous characteristics with increased permeability. Hemodialfiltration (HDF) is the treatment modality that combines diffusion and enhanced convection in order to facilitate removal of small molecular weight solutes. Moreover, small molecule removal is further increased with the use of high-volume OL-HDF. HDF is thus a more cardioprotective renal replacement therapy.

Recent randomized controlled trials (RCTs) have shown the survival advantage of HDF using high-convective volumes (23 L/session or 69 L/week prescription). In Peters et al.'s review [11] which is a pooled individual participant analysis of 4 RCTs, it was a observed that in patients receiving the higher delivered convection volume (>23 L per 1.73 m2 body surface area (BSA) per session), the longest survival benefit was seen with **Hazard Ratio (HR)** of 0.69 (95% CI: 0.47; 1.00) for cardiovascular disease mortality and HR of 0.78 (95% CI: 0.62; 0.98) for all-cause mortality.

In another study by Canaud et al. [12], which was a retrospective data collection from over 2000 patients with a minimum follow-up of 2 years, the relative survival rate of OL-HDF patients was found to increase at about 55 **L**–75 **L**/week of convection volume.
