Artificial kidney

Kidney failure

Kidneys are paired vital organs located behind the abdominal cavity at the bottom of the ribcage corresponding to the levels T12-L3 of the spine vertebrae. They perform about a dozen physiologic functions and are fairly easily damaged. Some of these functions include filtration and excretion of metabolic waste products, regulation of necessary electrolytes and fluids and stimulation of red blood cell-production. These organs routinely filter about 100 to 140 liters of blood a day to produce 1 to 2 liters of urine composed of wastes and extra fluid.

Kidney failure results in the slow accumulation of nitrogenous wastes, salts, water, and disruption of the body's normal pH balance. This failure occurs over a long period of time, and when the patient's renal function declines enough over the course of the disease, is commonly known as end stage renal disease (ESRD; which is also known as Level 5 or 6 kidney disease, depending on whether dialysis or renal replacement therapy is used). Detecting kidney disease before the kidneys start to shut down is uncommon, with high blood pressure and decreased appetite being symptoms that indicate a problem. Diabetes and high blood pressure are seen as the 2 most common causes of kidney failure. Experts are predicting that the demand for dialysis will increase as the prevalence of diabetes increases. Until the Second World War, kidney failure generally meant death for the patient. Several insights into kidney function and acute kidney failure were made during the war.

1 in 3 American adults are at a risk for developing kidney disease. Over 26 million American adults have kidney disease and they are not even aware of it. Of those individuals more than 661,000 people have kidney failure and 468,000 are on dialysis. Since there is a large population of individuals with kidney failure, there continues to be advancements in technology of artificial kidneys so that more people can have access to treatments.

The prevalence of home hemodialysis has been decreasing because of the disadvantages of it. It is expensive, time consuming and takes up a lot of space. In 1980, 9.7% of the dialysis population was on home hemodialysis and by 1987 the number dropped to only 3.6% of the total.

According to a 2011 report by the Organization for Economic Cooperation and Development, the United States of America has the second-highest rate of dialysis use among advanced countries after Japan. The United States also has the highest mortality rate of patients with ESRD. On average 20% of American ESRD patients die annually, which is more than twice that of Japan. The growth of dialysis facilities in the United States is the result of more Americans developing end-stage renal disease. From 2001 to 2011 the number increased by about 49.7% from 411,000 citizens to 615,000 citizens. In 2001 there were only 296,000 Americans on some form of dialysis. Ten years later that number increased to more than 430,000 as a result of chronic conditions developing such as diabetes and hypertension.

Need for a bioartificial kidney

Over 300,000 Americans are dependent on hemodialysis as treatment for kidney failure, but according to data from the 2005 USRDS 452,000 Americans have end-stage kidney disease (ESKD). Intriguing investigations from groups in London, Ontario and Toronto, Ontario have suggested that dialysis treatments lasting two to three times as long as, and delivered more frequently than, conventional thrice weekly treatments may be associated with improved clinical outcomes. Implementing six-times weekly, all-night dialysis would overwhelm existing resources in most countries. This, as well as scarcity of donor organs for kidney transplantation has prompted research in developing alternative therapies, including the development of a wearable or implantable device.

Artificial Kidney

Hemodialysis is a method for removing waste products such as creatinine and urea, as well as free water from the blood when the kidneys are in kidney failure. The mechanical device used to clean the patients blood is called a dialyser, also known as an artificial kidney. The other name for artificial kidney is also called a dialysis machine. Modern dialysers typically consist of a cylindrical rigid casing enclosing hollow fibers cast or extruded from a polymer or copolymer, which is usually a proprietary formulation. The combined area of the hollow fibers is typically between 1-2 square meters. Intensive research has been conducted by many groups to optimize blood and dialysate flows within the dialyser, in order to achieve efficient transfer of wastes from blood to dialysate.

Implantable Artificial Kidney

The implantable artificial kidney is a second project that is being developed by a nephrologist named William H. Fissell IV, MD, at the Vanderbilt University Medical Center. Fissell and his colleges have been working on the implantable artificial kidney for over a decade but recently received a 6-million-dollar grant in November 2015 to further continue the research and development of the project. The goal of this project is to create a bio-hybrid device that can imitate the functions of a healthy kidney by removing enough waste products to keep a patient from needing dialysis treatment. The key to the success of this device is the use of silicon nanotechnology and the microchip which is precious and can act as a natural filter. Fissell and his team have designed each pore (of the filter) to perform a specific function or task. The microchips will also act as a platform for which living kidney cells will reside and grow on and around the filters with the goal of imitating the natural functions of the kidney. The bio-hybrid device will not be in reach of the body’s immune response which allows it to be protected against being rejected by the patient's body. The device will be designed to be small enough to fit inside a patient’s body that will successfully operate with the patient’s natural blood flow. Fissel and his research team continue to make progress and expect the implantable artificial kidney to enter human trials by 2017.

Wearable artificial kidney

A wearable artificial kidney is a wearable dialysis machine that a person with end-stage kidney disease could use daily or even continuously. A wearable artificial kidney (WAK) is not available, but research teams are in the process of developing such a device. The goal is to develop a portable device that will be able to imitate the functions of the regular kidney. This device would allow for a patient to be treated twenty-four hours a day. With the development of miniature pumps, the idea of an effective wearable hemodialysis device has become more achievable. Many patients are already receiving a continuous peritoneal dialysis treatment which allows them to remain ambulatory. One of the problems with this treatment is that only a small portion of dialysis patients use peritoneal dialysis as their method of treatment because it requires large amounts of dialysate to be stored and disposed of throughout the treatment. In a healthy individual the kidneys filter blood for roughly 168 hours a week compared to an individual with end-stage renal disease whose treatment plan is to be on dialysis for approximately 12 hours a week. This treatment is inadequate and results in a lower quality of life as well as a high mortality rate for patients with end stage renal disease (ESRD). Therefore, there is a need for an around-the-clock device that will allow ESRD patients to be administered higher doses of dialysis continuously while still maintaining a normal life. The FDA has approved the first human clinical trial in the United States for a wearable artificial kidney designed by Blood Purification Technologies Inc. of Beverly Hills, California. The present prototype of the WAK is a 10-pound device, powered by nine-volt batteries, which connects to a patient via a catheter, and should use less than 500mL of dialysate. It is designed to run continuously on batteries which will allow patients to be ambulatory when wearing the device ultimately leading to a greater quality of life.The device is also designed to make improvement in other physiological aspects of the patient’s health such as improvement in volume control, a decrease in hypertension and sodium retention, as well as a decreased chance of developing cardiovascular disease and stroke.

Experiments of the Wearable Artificial Kidney

The wearable artificial kidney (WAK) has constantly been modified throughout the years for the better of people who have kidney failure. To try and make the WAK usable, several experiments have been conducted. While conducting these experiments for the WAK, similar goals are trying to be achieved. For example, a main goal that these experiments are trying to achieve is to make sure that the WAK can function like a regular kidney.

One experiment that took place included eight people who wore the WAK for four to eight hours. As the participants wore the WAK, several outcomes occurred. For example, one outcome during the experiment was that the fluid removal for the WAK was controlled correctly by an ultrafiltration pump. Another outcome that took place during this experiment was that a needle connected to the WAK ended up disconnecting itself. When this happened, the WAK was able to recognize this, and the blood stopped pumping. When the blood stopped pumping, the needle could be reinserted without the body losing a large amount of blood. As other research has been conducted, it has been argued that using an ultrafiltration pump may not be the best pump for the WAK. For example, research has found that by using a peristaltic pump instead, would allow a person to know their blood flow rate without having a sensor, which is needed in an ultrafiltration pump used in the experiment mentioned above. A change in the type of pump used for the WAK may be crucial because it could help make the device cheaper and more reliable for the public by not having a sensor. Another experiment conducted by Victor Gura involved seven patients with end stage kidney disease to wear a WAK device for 24 hours. During the experiment, Victor Gura and the rest of his team noticed that two participants WAK stopped working because of technology issues. This has been acknowledged by Victor Gura and he has said that this must be corrected before WAK can be released to the public.

After doing a lot of research on the WAK, several research questions have been answered. For example, researchers have found out that the WAK can work without an outlet because it has been able to function on a nine-volt battery. Although, it has been argued by researchers that using nine-volt batteries are not effective enough for the WAK because it does not power the device long enough and indirectly it makes the WAK less affordable when having to constantly change the batteries. Due to this, other energy sources are being explored, for example, researchers are seeing if fuel cells, wireless transmission of energy from an active source, or harvesting energy from the environment would be better ways to power the WAK for longer periods of time. Another important question that attracted a lot of attention was if the WAK would be light enough for someone to wear comfortably throughout the day. After conducting several experiments the answer to this question is yes, because people have been able to shower and sleep while wearing the device. Also, at the same time the WAK can weigh as light as ten pounds, but researchers are trying to make the device as light as five pounds. Several questions have been answered about the WAK, but many research questions are still left unanswered. Researchers are still trying to figure out if the WAK can be energy efficient, affordable, and if it can reuse small amounts of dialysate.

Implantable Renal Assist Device (IRAD)

Currently, no viable bioengineered kidneys exist. Although a great deal of research is underway, numerous barriers exist to their creation.

However, manufacturing a membrane that mimics the kidney's ability to filter blood and subsequently excrete toxins while reabsorbing water and salt would allow for a wearable and/or implantable artificial kidney. Developing a membrane using microelectromechanical systems (MEMS) technology is a limiting step in creating an implantable, bioartificial kidney.

The BioMEMS and Renal Nanotechnology Laboratories at the Cleveland Clinic's Lerner Research Institute have focused on advancing membrane technology to develop an implantable or wearable therapy for end-stage kidney disease (ESKD). Current dialysis cartridges are too large and require superphysiologic pressures for blood circulation, and pores in current polymer membranes have too broad of a size distribution and irregular features. Manufacturing a silicon, nanoporous membrane with narrow pore size distributions improves the membrane's ability to discriminate between filtered and retained molecules. It also increases hydraulic permeability by allowing the mean pore size to approach the desired cutoff of the membrane. Using a batch-fabrication process allows for strict control over pore size distribution and geometry.

Studies show human kidney cells were harvested from donated organs unsuitable for transplantation, and grown on these membranes. The cultured cells covered the membranes and appear to retain features of adult kidney cells. The differentiated growth of renal epithelial cells on MEMS materials suggests that a miniaturized device suitable for implantation may be feasible.

A UCSF-led effort to create an implantable artificial kidney for dialysis patients has been selected as one of the first projects to undergo more timely and collaborative review at the Food and Drug Administration.

The FDA announced on April 9, 2012 that it had chosen three renal device projects to pilot a regulatory approval program called Innovation Pathway 2.0, intended to bring breakthrough medical device technologies to patients faster and more efficiently.

The artificial kidney project, which is targeted for clinical trials in 2017, was selected for its transformative potential in treating end stage kidney disease and for its potential to benefit from early interactions with the FDA in the approval process.

The FDA effort will involve close contact between the federal agency and device developers early in the development process to identify and address potential scientific and regulatory hurdles and create a roadmap for project approval. The goal is to improve the projects’ overall chance of success, while reducing the time and cost of FDA review and maintaining safety. Lessons, the agency said, will inform approvals in other areas.