History of Sorbent Technology: Dialysis applications

Background

Hemodialysis requires approximately 120 liters of purified water per treatment for the preparation of dialysate. In many areas of the world, high quality water is not readily available. Additionally, the structure and size of traditional hemodialysis machines make adaptability to varying environments difficult. In response to the need for a versatile, portable dialysis machine which could be used in a variety of environments, sorbent systems for regeneration of dialysate were developed¹.

Central to the development of sorbent technology for dialysis was the need to remove nitrogenous waste products from the body. In 1920, experiments proved that activated carbon could remove nitrogenous waste products such as uric acid, creatinine and color from urine¹.

Historically, most sorbents were a form of activated coal and sorbent technology applications were concentrated in the control of environmental pollution.

Concepts and research in the early years

In the early 1960s, the Marquardt Corporation, an aerospace company in Van Nuys, California, employed sorbent technology in its government-funded aerospace programs for The National Aeronautics and Space Administration (NASA). The goal of those programs was to use sorbent chemistry to purify waste and drinking water².

In 1966, the concept of regenerating rather than discarding spent hemodialysate was suggested by Mr. A. Johnson, an engineer at Marquardt Corporation.  While engaged in the purification research of agricultural waste water, he thought that the same concept could be applied to waste hemodialysate³.  Drs. Arthur Gordon and Morton Maxwell of Cedars-Sinai Medical Center believed that development of the concept could provide information on uremic toxins and lead to a wearable artificial kidney. Work on the project commenced in June of 1967, involving a joint effort between the Marquardt Company and Cedars-Sinai Medical Center⁴.

Dr. L Marantz developed and designed the first suitable sorbent cartridge consisting of zirconium phosphate, hydrated zirconium oxide and activated carbon. Uremic dogs were successfully maintained using this cartridge to regenerate hemodialysate. Further dog trials were successful and human studies were started in 1968³.

The early achievements of the sorbent cartridge led to a project based on the concept and development of a complete dialysate supply system using sorbent technology⁴. The project’s goal was to develop a new dialysate supply system that would eliminate the need for large volumes of high quality water and plumbing installations through continually regenerating and reusing a few liters of dialysate. An appropriate combination of sorbents would remove all toxins, maintain the essential concentration of electrolytes and control acidosis and other metabolic disorders⁴. This new development would bring to fruition an innovative concept in hemodialysis treatments in which the principle of passing dialysate through the system once and then down the drain would be replaced by the regeneration of dialysate⁴.

After nearly 5 years of research and development and in-vitro, preclinical and clinical studies, the Recirculating Dialysate System (REDY), was placed on the market in 1973^3,4.   The REDY system’s components included the REDY machine, a sorbent cartridge and a dialysate storage container.

 

The launch of a new product

Initially, the major market for the REDY system was home hemodialysis³. There was no need to modify the home for installation of plumbing and thus the sorbent system was less expensive to install and operate than a single-pass system. In addition, the system was portable permitting patients to dialyze anywhere, including while traveling⁵. Dr. L. Lewin was the first nephrologist to use the REDY system to dialyze acute renal failure patients³.  By 1975 an estimated 10,000 hemodialysis treatments per month were utilizing the REDY system⁶.

Although the REDY system was used worldwide, emerging economic transformations, medical issues and industry innovations stimulated a decline in the use of the REDY system in the United States. In 1973, the U.S. government introduced reimbursement for the End Stage Renal Disease (ESRD) program. An unanticipated result of the ESRD program was a significant reduction in home hemodialysis, as in-center hemodialysis became more widely available.

Additionally, starting in 1981, a number of reports appeared implicating the REDY system as a cause of aluminum toxicity in patients on maintenance dialysis. In most cases less than 10ug/L of aluminum was present in the effluent from the sorbent cartridge containing hydrated zirconium oxide in the acetate form³. Unacceptable levels were present when bicarbonate dialysate was used with a cartridge containing hydrated zirconium oxide in the chloride form. Although this cartridge was immediately taken off the market³ and replaced with cartridges with negligible aluminum, the perception of potential issues with aluminum impeded larger acceptance of the REDY system. Current cartridge design technology has eliminated the aluminum toxicity issue.

Advantages and outcomes

Throughout the 1980s, sorbent dialysis technology continued to improve with chemical refinements and system design. Because of its portability, minimal resource consumption and simplicity, the REDY system served as the U.S. Army’s deployable dialysis equipment. During the 1988 earthquake that struck northern Armenia, international dialysis teams participating in the medical relief mission brought the REDY system⁷.  The REDY system provided the only functional dialysis available because of the extensive damage to the existing local water and power systems.

By 1991, peer reviewed medical publications commented the “effectiveness and safety of the sorbent system have been extensively proved in patients with chronic and acute renal failure, and in both stable and critically ill patients⁸”.

 

Sorbent technology’s sustainability

Though manufacturing of the REDY machine was discontinued in 1994⁷, use of the sorbent cartridge endured fulfilling the growing need of providing dialysis in a wide variety of clinical treatment environments. 

The nearly 40 year history of sorbent dialysis has shown the adaptability of this unique technology. Today, the need for a self-contained, transportable system that produces fresh dialysate utilizing a sorbent cartridge and only 6 liters of potable tap water is greater than ever. Current investigations incorporating the use of sorbent-based products not only offer the potential to provide portable and potentially wearable renal replacement therapy², but expand the role of sorbents in renal replacement therapy.

1. Shapiro WB. The current status of sorbent hemodialysis. Sem in Dial 4:40-45, 1991
2. Hansen SK. The history of sorbent dialysis. Retrieved April 18, 2008, from www.renalsolutionsinc.com
3. Roberts M. The regenerative dialysis (REDY) sorbent system. Nephrology 4:275-278, 1998
4. Greenbaum MA and Gordon A. A regenerative dialysis supply system. Dial Transplant 1:18-24, 1972
5. Roberts M. The status of sorbent technology in hemodialysis treatment. Clinical Neph 26:(Suppl 1) 44-46, 1986
6. Henderson L. Redy or not. ASAIO Journal 2:49-53, 1979
7. Welch PG. Deployment dialysis in the U.S. Army: History and future challenges. Military Medicine 165:737-741, 2000
8. Reyes A, Turchetto E, Bernis C, Cereijo E. Acid-base derangements during sorbent regenerative hemodialysis in mechanically ventilated patients. Critical Care Med 19:554-559, 1991