Expanded Hemodialysis

Innovative Clinical Approach in Dialysis

C. Ronco, C., Ronco, Claudio Ronco, Claudio, Ronco

• Publisher: S. Karger
• Year: 2017
• Print ISBN: 9783318061161
• eBook ISBN: 9783318061178
• Topic: Medicine
• Subtopic: Medical Technology & Supplies

Despite constant significant advances, cardiovascular as well as more general outcomes of hemodialysis treatment remain unsatisfactory. The introduction of innovative 'high retention onset' membranes has led to the development of a new treatment modality called 'expanded hemodialysis' (HDx), which is the focus of this book. This new therapy is likely to benefit end-stage kidney disease patients, thanks to enhanced removal of molecules retained by current dialysis techniques. HDx is simple to set up and application does not require special hardware or specific nursing skills. This book contains emerging evidence and fascinating new hypotheses on HDx. It is highly recommended for all physicians and healthcare professionals who are caring for dialysis patients and are seeking innovation and improved care solutions. It will also be of considerable interest to students and fellows.

Ronco C (ed): Expanded Hemodialysis – Innovative Clinical Approach in Dialysis.
Contrib Nephrol. Basel, Karger, 2017, vol 191, pp 84–99 (DOI: 10.1159/000479258)

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Solute Transport in Hemodialysis: Advances and Limitations of Current Membrane Technology

William R. Clark^a · Dayong Gao^b · Mauro Neri^c · Claudio Ronco^{c, d}

^aDavidson School of Chemical Engineering, Purdue University, West Lafayette, IN, and ^bDepartment of Mechanical Engineering, University of Washington, Seattle, WA, USA; ^cInternational Renal Research Institute of Vicenza (IRRIV) and ^dDepartment of Nephrology, San Bortolo Hospital, Vicenza, Italy

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Abstract

Extracorporeal therapy for end-stage renal disease is now provided to more than three million patients globally. Nearly all treatments are performed with filters containing hollow fiber membranes, removing solutes and water by diffusion, convection, and ultrafiltration. In this review, we will provide a detailed quantitative analysis of the transport processes involved in different hemodialysis (HD) therapies. We will also report some technical aspects of hollow fiber membranes and filters composed of them along with the mechanisms of solute and water removal for such devices. Diffusive mass transfer will be assessed according to the three major aspects of a hollow fiber filter (blood compartment, membrane, and dialysate compartment). With regard to convective transport, the importance of internal filtration as a solute removal mechanism in high-flux HD will be highlighted, along with the critical role that blood/membrane interactions assume in filtration-based therapies.

© 2017 S. Karger AG, Basel

Introduction

Extracorporeal therapy for end-stage renal disease is now provided to more than three million patients globally. Nearly all treatments are performed with filters containing hollow fiber membranes, removing solutes and water by diffusion, convection, and ultrafiltration. The routine use of these therapies belies their technical complexity and dynamic nature. In this review, we will provide a detailed quantitative analysis of the transport processes involved in different hemodialysis (HD) therapies. We will also report some technical aspects of hollow fiber membranes and filters composed of them along with the mechanisms of solute and water removal for such devices.

Hollow Fiber Membranes

Solute Characteristics

Uremic retention molecules represent a spectrum of substances, normally cleared by the native kidney, whose concentration in blood increases significantly as renal function decreases. Several of these molecules are efficiently removed by the current HD techniques, although limitations to solute transport may occur due to the intrinsic characteristics of the molecule, including molecular weight, molecular radius, hydrophicity, electrical charges, and protein binding. As discussed below, diffusive transport rates tend to decrease with increasing molecular weight or radius. This limitation has two basic determinants: the diffusion coefficient of the molecule and the possible restriction imposed by the membrane. The combination of diffusion and convection in HD is intended to overcome this limitation and optimize solute removal in the widest possible molecular weight spectrum.

Hollow Fiber Design

An individual hollow fiber can be viewed as a solid cylinder in which the central region has been removed (“cored out”) to form an annular blood compartment [1]. The process of manufacturing (“spinning”) a hollow fiber membrane is complex, and incorporates aspects of a broad array of scientific disciplines, including polymer chemistry, thermodynamics, reaction kinetics, and chemical engineering [2]. Although clear differences exist among the different types of membranes used clinically, a number of common features apply. From a structural perspective, most hollow fibers have a relatively standard inner (blood compartment) diameter (approximately 180–220 µm) and length (20–24 cm). These parameters are dictated essentially by the operating conditions existing during HD and are the result of a compromise between opposing forces. On one hand, a relatively small hollow fiber inner diameter is desirable because it provides a short diffusive distance for solute mass transfer. At a given blood flow rate, a smaller bore fiber also creates a higher shear rate, resulting in greater attenuation of blood-side boundary layer effects [3]. However, the degree to which the inner diameter can be reduced is limited. Flow along the length of a cylinder (i.e., axial flow) of fluids such as water and blood (i.e., Newtonian fluids) is governed by the Hagen-Poiseuille law [4]:

where Q_B is the blood flow rate, ΔP is the axial pressure drop, µ is the blood viscosity, L is the fiber length, and r is the hollow fiber radius. A specific application of this equation is blood flow from the arterial to venous end of a hollow fiber membrane during HD. A more general form of equation 1 is:

From equations 1 and 2, the resistance (R) to blood flow is:

Due to the inverse relationship between flow resistance and r⁴, a small decrease in the inner diameter of the hollow fiber induces a large increase in flow resistance. Equation 3 also demonstrates that increases in fiber length and hematocrit (Hct; through an effect on blood viscosity) are associated with an increase in flow resistance. In turn, as indicated by equation 2, an increase in flow resistance results in a proportional increase in axial pressure drop at constant blood flow rate.

Surface Area

For a particular hollow fiber, the inner annular surface represents the nominal blood compartment surface and is theoretically the maximum area available for blood contact. For the entire group of fibers comprising a filter (i.e., the fiber bundle), the total nominal surface depends on the fiber length, inner diameter, and overall number of fibers, the latter of which varies generally from approximately 9,000 to 16,000. For calculation of dialyzer membrane surface area, the surface area of an individual fiber can be estimated by using the formula for a cylinder:

Based on assumed values of r = 100 µm (10^-4 m) and L = 24 cm (0.24 m), the surface area of an individual fiber can be calculated as 1.51 × 10^-4 m². For a relatively large filter (n = 14,000):

Fig. 1. Idealized membrane model in which all pores have the same radius and are cylinders perpendicular to the blood and dialysate flows. Reprinted with permission from Takeyama and Sakai [5].

Effect of Membrane Pore Characteristics on Water Permeability

To provide a rough quantitative estimate of parameters related to pore characteristics of a hollow fiber membrane, a straight cylindrical pore model can be used as a first approximation. As shown in Figure 1 [5], this model assumes that the membrane’s pores have the same radius (r_p), which is larger than the radius (r_s) of the hypothetical solute given. In addition, the directional orientation of the parallel cylinders is assumed to be perpendicular to the flow of blood and dialysate. As noted above, the Hagen-Poiseuille law governs the fluid flow through cylindrical tubes in many situations, applying also to transmembrane ultrafiltrate flow through the pores in this model. As such, the rate of ultrafiltrate flow is directly related to the fourth-power of the pore radius (i.e., r⁴) at constant transmembrane pressure.

A more sophisticated approach accounts for the fact that membrane pores are not “perfect” cylinders [6]:

In this equation, K_f is the hydraulic permeability of the membrane, n is the number of pores per unit area (i.e., pore density), r is the pore radius, τ is a factor accounting for pore tortuosity, µ is the ultrafiltrate viscosity, and Δx is ...

Table of contents

• Cover Page
• Front Matter
• The Evolving Patterns of Uremia: Unmet Clinical Needs in Dialysis
• Middle-Molecule Uremic Toxins and Outcomes in Chronic Kidney Disease
• Uremia Retention Molecules and Clinical Outcomes
• End-Stage Renal Disease, Inflammation and Cardiovascular Outcomes
• The Cardiovascular Burden in End-Stage Renal Disease
• Inflammation and Protein-Energy Wasting in the Uremic Milieu
• Inflammation: A Key Contributor to the Genesis and Progression of Chronic Kidney Disease
• Solute Transport in Hemodialysis: Advances and Limitations of Current Membrane Technology
• Membrane Innovation in Dialysis
• Multidimensional Classification of Dialysis Membranes
• Modeling of Internal Filtration in Theranova Hemodialyzers
• The Rationale for Expanded Hemodialysis Therapy (HDx)
• Expanded Hemodialysis Therapy: Prescription and Delivery
• Effects of Hemodialysis Therapy Using Dialyzers with Medium Cut-Off Membranes on Middle Molecules
• The Place of Large Pore Membranes in the Treatment Portfolio of Patients on Hemodialysis
• Large Middle Molecule and Albumin Removal: Why Should We Not Rest on Our Laurels?
• Effects of Expanded Hemodialysis Therapy on Clinical Outcomes
• Author Index
• Subject Index
• Back Cover Page