**1. Introduction**

In 2010, more than 2 million individuals worldwide were receiving maintenance dialysis, and this number was expected to increase to 5.4 million by 2030 [1]. Despite improvements in technology and medical care, the mortality rate of patients on maintenance dialysis remains high, with 55% dying within 5 years of initiating dialysis therapy [2]. It has even been shown that the survival in maintenance dialysis patients was lower than that for patients with several types of cancer [3].

This mortality is largely related to the accumulation of uremic toxins. The existence of an interaction between uremic toxins, inflammation and/or oxidative stress, and cardiovascular mortality is well reported in the various epidemiological studies. In accordance with the European Uremic Toxins Work Group (EUTox) database, there are currently more than 153 uremic solutes listed, and that number should increase over time [4].

According to the molecular weight of these uremic toxins, they are divided into six classes, including small water-soluble molecules (<500 Da), protein-bound uremic toxins (PBUTs; mostly <500 Da), small-middle molecules (0.5–15 kDa), mediummiddle molecules (15–25 kDa), large-middle molecules (25–58 kDa), and large molecules (>58 kDa) [5]. Complications, such as anemia, neuropathies, osteodystrophy,

dialysis-related amyloidosis, accelerated atherosclerosis, and cardiovascular complications, have been correlated with uremic toxins in the molecular range of 5–50 kDa [6].

Originally, membranes for hemodialysis were designed to remove small solutes, such as urea and creatinine. Since then, technological progress has continued to develop to improve the clearance of uremic toxins. The advent of ultrafiltration control systems led to the development and use of high-flux (HF) membranes that allowed improved middle molecule removal. Further evolution in technology led to the development of a new class of membranes referred to as super-flux or high cutoff (HCO), with albumin loss representing a limitation to their practical application. Hemodiafiltration (HDF) at high volumes (>23 L/1.73 m2/session) has produced some results on middle molecules and clinical outcomes, although complex hardware and high blood flows are required. A new class of membranes has recently been developed with characteristics allowing high clearances of solutes in a wide spectrum of molecular weights without significant loss of albumin. These membranes originally defined as "medium cutoff" are probably better classified as "high retention onset" and have introduced a new concept of hemodialysis called "expanded hemodialysis" (HDx). It is a simple dialysis technique, requiring no sophisticated equipment or special training for nurses, making its application possible in every setting once the quality of the dialysis fluid is guaranteed to ensure the safe conduct of the dialysis session.

In this chapter, we describe the characteristics of the medium cutoff membranes, their potential benefits, and considerations for the prescription and delivery of HDx.
