**2. Medium cutoff (MCO) membranes characteristics**

#### **2.1 Radius and distribution of membrane pores**

Dialyzers' surface properties are crucial factors in evaluating the membrane performance. The morphological characteristics, such as mean pore size, pore size distribution, surface porosity, and pore tortuosity, influence the molecular weight removal spectrum and membrane clearance. For the MCO membrane, the size of the pores is intermediate between those of the HF and HCO membranes [7]. The MCO membrane has an effective pore radius of 3.0–3.5 nm after contact with blood, allowing for the removal of an expanded range of uremic toxins [8]. The distribution of the pores in dialysis membranes is not uniform. The more the membrane pore size distribution curves are deviated to the right, the better the removal of large middle molecules, but the risk of albumin loss is higher, it is the case with HCO membranes [9]. To improve the clearance of large middle molecules, while avoiding the loss of albumin, the distribution of the pore sizes has had to be "tightened." This is the principle used in MCO membranes.

In addition to the tight distribution of pores, there are two major differences between the MCO membrane and with HF dialyzer: first, the wall thickness is decreased from 50 μm to 35 μm, which allows a shorter diffusion path, second, the diameter of hollow fibers inside MCO membranes is reduced from the standard 200 μm to 180 μm, to improve convection and internal filtration (see internal filtration chapter below).

#### **2.2 Sieving curves**

One of the main characteristics of a dialysis membrane is its permeability in terms of sieving capacity. The sieving curve shows a progressive reduction of the observed

#### *Expanded Hemodialysis Therapy: From the Rational to the Delivery DOI: http://dx.doi.org/10.5772/intechopen.110262*

values for solute sieving as the solute molecular weight increases. Molecular weight cutoff (MWCO) is defined as the lowest molecular weight (in daltons) at which greater than 90% of a solute with a known molecular weight is retained by the membrane (sieving = 0.1). On the other side of the sieving curve, the molecular weight at which 10% of the solute is retained (sieving = 0.9) defines the retention onset of the membrane (MWRO). A classification scheme was proposed in which the MWCO and the MWRO are utilized in combination to define different dialyzer classes. As the separation between MWRO and MWCO decreases, the profile of the curve becomes steeper, resulting in increased removal of large uremic toxins and decreased loss of albumin [10]. Based on this concept of selectivity of the sieving coefficient, we can now differentiate the different membranes. MCO membrane, although presenting a similar MWRO to the HCO membrane, displays a completely different behavior. While MWRO for the HF membrane is in the range of 1200 Da (vitamin B12), MWRO for the MCO membrane is in the range of 12,000 Da (β-2 microglobulin). On the other side, when comparing MCO and HCO membranes, we see that these two membranes will have the same performance when extracting middle molecules, such as β-2 microglobulin, with a high MWRO for the two membranes, however, the MCO membrane has a much lower MWCO for albumin, thus making it possible to limit the leaks of albumin. For this reason, the MCO membranes have also been defined as high retention onset membranes (HRO), with the aim of optimizing clearances of medium to large MW solutes while avoiding significant albumin loss [11].

#### **2.3 Internal filtration**

Clearance of middle molecules cannot be improved by diffusive phenomena alone; convective clearance must also be optimized. Let us remember that convective clearance (K) results from the product of the UF rate (Qf) and sieving (S) of the selected molecule (K = Qf x S). Because the sieving of the selected molecule is low, the only way to increase K is to increase Qf. The on-line hemodiafiltration (OL-HDF) has made high convection rates possible thanks to the combined pre- and post-dilution configuration, but complex hardware and high blood flows are required. Due to the specific internal properties of the MCO membrane, HDx with MCO membranes represents a simpler way to improve convective clearance, with no need for fluid substitution. The ultrafiltration control system of regular hemodialysis machines provides the exact amount of net filtration required for the scheduled weight loss of dialysis patients. In OL-HDF, large amounts of ultrafiltration (UF) are achieved with high transmembrane pressure (TMP) and then replaced in the venous line after multiple steps of filtration of fresh dialysate. In HDx, the convection flow is maintained in the first part of the MCO membrane, based on excessive ultrafiltration due to the mentioned characteristics of this membrane, but it is compensated by the mechanism of internal filtration inside the filter, which takes place at about the terminal part of this membrane, and is considered as replacement fluids to the ultrafiltration [6].

The remarkable amount of convection in the proximal part is resulting from an increased end-to-end pressure drop. Internal filtration compensates for the excessive filtration rate in the distal part [12]. Thus, the convective transport of MCO membranes increases by a large margin along the length of the fibers, which makes it possible to remove large molecules with low diffusion coefficients. Indeed, to improve solute transport and avoid protein stagnation at the blood membrane interface, the diameter of hollow fibers inside MCO membranes is reduced from the standard 200 μm to 180 μm [13], which increases the rate of wall shear and blood flow velocity

[14]. Reducing the diameter and thickness of the membrane can increase internal convection by up to 30%. The combination of hydraulic permeability and geometric structure of the fibers enhances the process of internal filtration in MCO membranes [15]. MCO membranes are thus characterized by higher permeability than classic high-flux membranes. Blood flow ≥300 mL/min and dialysate flow ≥500 mL/min is sufficient to achieve optimal clearance in the system [6, 11].
