In hemodialysis, the dialyzer is often called the “artificial kidney.” At its core is the hemodialysis membrane, a filter that performs the life-sustaining task of cleansing the blood of individuals whose kidneys have failed. This semipermeable membrane separates blood from a specialized fluid called dialysate, allowing waste products and excess fluid to pass out while retaining blood cells and proteins.
Blood is circulated on one side of the membrane and dialysate flows on the other, creating the environment for this exchange. This technology is a form of renal replacement therapy, supplementing the filtration function that healthy kidneys normally provide.
Mechanism of Solute and Fluid Removal
The hemodialysis membrane cleans the blood through two main physical processes: diffusion and ultrafiltration. Diffusion is the primary mechanism for removing small waste molecules, such as urea and creatinine. This process works on a concentration gradient, where solutes move from an area of higher concentration (the blood) to one of lower concentration (the dialysate), which is free of these waste products. The rate of diffusion is influenced by the membrane’s surface area, its thickness, and the size of the waste solutes.
To maintain this gradient, fresh dialysate is constantly pumped into the dialyzer, and many systems use a countercurrent flow design where blood and dialysate flow in opposite directions to maximize efficiency. Fluid removal is achieved through ultrafiltration, which is driven by a pressure gradient. The higher pressure on the blood side of the membrane physically pushes excess water out of the blood. Convection is the process where dissolved solutes are dragged along with the water as it moves, an action effective for clearing “middle molecules” too large for removal by diffusion alone.
Classification of Membranes
Hemodialysis membranes are classified based on their pore size and permeability. The most fundamental distinction is between low-flux and high-flux membranes. Low-flux membranes have smaller pores and are less permeable to water. Their primary mechanism for solute removal is diffusion, making them effective at clearing small molecules like urea.
High-flux membranes feature larger pores and have much higher permeability to water and larger molecules. This structure allows them to use both diffusion and convection for a more comprehensive removal of toxins, including middle molecules like beta-2 microglobulin. The choice between them depends on the patient’s clinical needs.
A newer category, medium cut-off (MCO) membranes, further enhances the clearance of middle molecules. MCO membranes have a pore size larger than high-flux membranes but are still small enough to prevent significant loss of albumin, an important blood protein. This design increases convective transport within the dialyzer, allowing for “expanded hemodialysis” that more closely mimics a healthy kidney’s filtration.
Membrane Materials and Composition
The materials used for hemodialysis membranes have evolved from natural to synthetic polymers to improve performance and patient tolerance. Historically, the first membranes were cellulosic, derived from cotton, with the most common being cuprophane. While effective for their time, these early membranes are known to be less biocompatible.
Modern hemodialysis relies almost exclusively on synthetic membranes, which offer superior performance and are better tolerated. The most common materials are polysulfone (PSu) and its derivative, polyethersulfone (PES), which are favored for their high permeability and strength. Because these polymers are naturally hydrophobic (water-repelling), they are blended with hydrophilic (water-attracting) agents like polyvinylpyrrolidone (PVP) to reduce interactions with blood components.
Other synthetic materials used include polymethylmethacrylate (PMMA) and polyacrylonitrile (PAN). The continuous development of these synthetic materials focuses on optimizing the membrane structure to enhance solute removal and minimize adverse reactions.
Biocompatibility and Clinical Considerations
Biocompatibility in hemodialysis refers to the biological response that occurs when a patient’s blood contacts the dialyzer membrane. While an ideal membrane would be inert, all materials trigger some level of reaction. These interactions can activate biological pathways, including the coagulation and complement systems, which are part of the body’s immune and inflammatory responses. The magnitude of this activation depends heavily on the membrane’s material and surface characteristics.
A strong inflammatory response can cause acute symptoms during a dialysis session and may contribute to long-term complications. One indicator of a bio-incompatible reaction is the activation of the complement system. When activated, the complement cascade produces molecules that can lead to a temporary drop in white blood cell count and other inflammatory effects.
Older cellulosic membranes, such as cuprophane, are known to cause strong complement activation due to hydroxyl groups on their surface. In contrast, modern synthetic membranes, like those made from polysulfone, are more biocompatible. Their surfaces are smoother and modified to be more hydrophilic, reducing the interactions that initiate these inflammatory cascades. This improvement has been a major advance in making hemodialysis safer and better tolerated.