Uremia, a build-up of fluid, electrolyte, and toxins in the blood stream is a serious complication of failing kidneys. It is treated with hemodialysis, a process that uses a semi-permeable membrane (dialyzer) to remove wastes and restore the proper balance of fluid and electrolytes.
Historically, these membranes were made from cellulose (e.g., cuporphane) and sterilized using formaldehyde. However, residues of agents used in the manufacture of the membranes, including formaldehyde, were associated with a constellation of adverse patient reactions, known commonly as “first use syndrome.” To avoid this, as well as to manage high cost of early membranes, dialyzer re-use became a common practice.
While re-use of dialysis membranes has largely been shown to be safe with the implementation of stringent re-use disinfection processes, these processes can be challenging to maintain. Successful re-use is susceptible to disinfection process breakdowns in automation, as well as a need for human intervention in the multi-step process. Therefore, reuse comes with an additional significant burden of maintaining training standards, regulatory documentation, and a stringent quality assurance program.
The medical disadvantages of cellulose-based membranes, combined with the cost and complexity their manufacture, led to the development of synthetic polysulfone membranes. By 1999, only 5% of dialyzers were still being made from cellulose.
Some of the advantages of synthetic membranes include:
- Synthetic membranes can be sterilized with ethylene oxide, which can easily be rinsed from the dialyzer, as well as steam or radiation-based sterilization, thereby limiting exposure to toxic formaldehyde residue.
- Increased biocompatibility of synthetic membranes limits activation of the patient inflammatory response.
- Synthetic membranes, known as high-flux membranes, can be manufactured with a consistently larger pore size. The larger pore size enables more rapid diffusion of small molecules, compared to the older cellulose or mixed-cellulose membranes. They also allow removal of substances, such as beta-2 microglobulin, which could not pass through the smaller pore size of the cellulose membranes. Beta-2 microglobulin has been implicated in a number of adverse events in long-term dialysis patients so removing it is beneficial.
- Synthetic membranes work as a sponge as well as a filter, allowing adsorption of toxic molecules, such as endotoxin, that may be present in the dialysate (the fluid used to clean the blood). When endotoxin passes into a patient’s bloodstream via the dialysate, it produces multiple acute and chronic reactions. Clinical complications range from anaphylaxis to chronic inflammation associated with the development of coronary artery disease. The removal of endotoxin by synthetic membranes is associated with significant advantages.
- A 2012 systematic review of the use of high-flux membranes by the Cochrane Collaboration group concluded that high-flux membranes decreased cardiovascular events. It was estimated that three cardiovascular deaths can be prevented for every 100 dialysis patients treated for two years. Thus, there is data to compel the ongoing use of high-flux synthetic membranes.
The decline of re-use
In 1982, 82% of dialysis was done with reuse dialyzers. Studies in 2002 by the National Kidney Foundation and others demonstrated that the ongoing high utilization of reuse in the United States was being driven largely by the economics of a constrained reimbursement system. While the cost of making these high-flux membranes has been falling, they have historically been high. It is this high cost that has largely driven the ongoing practice of reuse of these membranes as opposed to single-use of the dialyzer.
As part of the evolution of dialyzer use, and acknowledging the disadvantages of reuse, Fresenius Medical Care-North America, the largest integrated manufacturer and dialysis provider, moved away from reuse in the early part of the last decade. Consequently, by 2005, the amount of reuse dialysis in the United States dropped to 61%. The dialysis industry as a whole, however, has not had the benefit of being simultaneously a dialysis service provider and a dialyzer manufacturer; therefore, the practice of reuse has persisted.
With an increasing number of dialysis membrane manufacturers having become available, as well as improvements in membrane manufacturer technology driving down production costs, the economic impetus, while still present for reuse, has decreased. Increasingly, it has become more and more difficult to ignore the advantages of single-use both from a medical and health care delivery perspective.
As such, mid-size dialysis providers, such as the one I am affiliated with—the not-for-profit Satellite Dialysis—have moved toward implementing single-use across the company. It is likely that this trend will continue amongst large and mid-size providers.
The challenges of single-use dialysis
Single-use dialysis comes with its own challenges. Single-use, by its very nature, dramatically increases the amount of medical waste generated as part of ongoing treatment.
Medical waste management itself is associated with significant direct costs, as well as critical environmental impacts. Medical waste management continues to emerge as an important area of research and development.
The bottom line
Dialysis health care delivery continues to rapidly evolve, and the move to single-use dialyzers is but one example of how improvements in technology can help improve patient outcomes.
Reference: Lacson and Lazarus, Seminars in Dialysis, 2006