iRAD: The Kidney Project Abstract The kidney is one of the most important organs in the human body. It removes waste and regulates various different compounds found in the blood stream. Individuals suffering from end stage renal disease have kidneys that can no longer function properly and are in need of assistance either through dialysis or a transplant. A new remarkable device called the implantable renal assist device or iRAD is on its way to helping hundreds of thousands of people with the disease get back to their daily lives. Introduction Most of us have never thought twice about our kidneys and the important role they play in our lives nor do we realize our bodies would cease to function without at least one of them. The recent rapid improvement in technology has led to the availability of bioartificial instruments that can replace failing organs. Until now the kidney was one of a kind, but researchers at the University of San Francisco have started to develop the first implantable bioartificial kidney, iRAD. Dr. Shuvo Roy, the head researcher for the project, states the iRAD will “carry out approximately 60-75 percent of the functions of a healthy kidney” [1]. What your kidneys do for you Before I can introduce what the bioartificial kidney does, I need to review the various jobs performed by the kidneys that are pertinent for life. One of the most important roles of the kidney is to remove the various waste products in the blood that are created from the normal wear and tear of tissues and the by-products that are not used by the body. The blood first enters the kidneys with both waste products and beneficial nutrients. These waste products are then removed from the blood by a multitude of different units and tubules throughout the kidney without displacing most of the beneficial nutrients. The kidneys regulate some chemicals, such as sodium, by either dispensing it back into the blood or with the wastes [2]. Before the clean blood is released to circulate the body, the kidney produces hormones that are to be deposited in the stream [2]. Some of the most important hormones help with the absorption of calcium to create strong bones, the active form of Vitamin D, and help create more red blood cells [1, 2]. Kidney Failure Kidney failure is still not completely understood. However, researchers do know that kidney diseases cause the tissues in the kidneys that filter toxins out of the blood, called the nephrons, to slowly cease to function [2]. People who suffer from diabetes, have high blood pressure or have kidney failure that runs in their family are the most likely to develop kidney failure some time in their lifetime [3]. Chronic kidney failure, CKF, is the gradual decrease of the ability of the kidney to perform the various jobs that are pertinent to survival [3]. Once the kidneys irreversibly lose 85 to 90 percent of overall function, the patient has reached end stage renal disease in which they cannot survive without a transplant or dialysis [3]. Dialysis is a temporary solution for end stage renal disease while waiting for a transplant that may never come. The Need There are 26 million people in the United States that have been diagnosed with chronic kidney disease, and this number has been increasing by eight percent over the past five years [3, 4]. In addition, 600,000 people in the United States per year are diagnosed with end stage renal disease and only 90,000 patients are on the transplant list [5]. There is a blatant need to not only save the lives of hundreds of thousands of people, but also to help them live their lives as though they had a perfectly functioning kidney. With end stage renal disease, dialysis needs to be performed several times a week for on average three to four hours each session, and researchers have found that numerous individuals have lost their jobs due to the time commitment of dialysis [6]. Although most patients use dialysis three times a week, studies have shown that when dialysis was done daily for several hours at a time the patient’s health increased [7]. Dialysis is normally done in a hospital but can be done in the comforts of home. However, researchers have seen that numerous people do not use at-home dialysis due to unfamiliarity with the machinery and the various adjustments that need to be made during the procedure [6, 4]. A device with which these patients could go on with their daily activities would greatly decrease the number of unemployed individuals on dialysis. This would also decrease the number of individuals with this chronic illness who suffer from bouts of depression [6]. Individuals who can no longer partake in activities that were once easy may start to identify with themselves differently [8]. This transition can put quite a mental and emotional strain on the individual, which can lead to a feeling of sorrow [8]. Transplantation, while effective, is in itself not a complete fix due to the need of “immunosuppressant medication to prevent rejection” of the transplant by the body [5]. This medication reduces the activity of the immune system and therefore leaves the patient at risk for various infections and cancers [5]. The New Kidney As shown in Figure 1, the iRAD contains two completely separate biocompatible compartments that are connected together with various tubing into a space about the size of an average coffee cup [9]. A tube is connected to the iliac vessel and from here blood enters the first compartment and is filtered through a vast array of silicon membranes using blood pressure as the motive force [6, 9]. Once the toxins have been eliminated from the blood, the filtrate is then transported through a tube to the adjacent compartment, the bioreactor, where it is processed [9]. Within the bioreactor are renal or kidney cells that carry out the separation process [9]. The wastes are separated from the filtrate in the bioreactor and transported through a tube to the bladder for removal from the body [9]. The minerals, chemicals, and electrolytes that are to be used by the body are transported from the bioreactor to the vena cava for circulation [9]. Figure 1. The implantable renal assist device in comparison to an average coffee cup [9]. Putting the iRAD together Filtering System To achieve what happens naturally in the kidney, silicon membranes made by microelectromechanical systems or MEMS are used to create a filtrate [9]. As seen in Figure 2, together these membranes, known as the hemofilter, take the shape of the natural kidney through the use of “uniform, highly porous and elongated silt-shaped structures” throughout the surface [9]. A special polymer, poly(ethylene glycol) or PEG, coats the area that comes into contact with the blood stream in order to reduce the following: formation of blood clots in the vessel known as thrombosis; any accumulation of unwanted material that could decrease the function of the membrane known as fouling; and decrease the amount of protein absorption from the blood [7, 9]. This polymer also helps increase blood compatibility and decrease rejection by the body [7]. The blood is pushed through the silicon filter by the natural pressure found in the arteries instead of a pump and therefore does not need a power supply [9]. This filtrate contains sugar, salts, nutritious chemicals, and wasteful chemicals in an aqueous solution. Bioreactor The waste created by the body then needs to be separated from the useful chemicals and deposited in the bladder for removal. The useful sugars and chemicals needed by the body for metabolic uses are deposited back into the blood stream and water is also reabsorbed into the bloodstream for hydration purposes by the renal cells in the bioreactor [9]. Researchers have found that tissue engineered human renal tubules both “grow and maintain” the appropriate amount of renal cells needed to perform natural kidney functions such as maintaining water and electrolyte balance in the blood and some metabolic functions while impeding the reabsorption of any toxins into blood stream [9]. Figure 2. A description of the two compartments of the iRAD [14]. Potential Problems This device sounds perfect, so what could go wrong? The potential problems of miniaturizing a dialysis machine that occupies the same amount of space as a large cabinet into the size of a coffee cup is a somewhat daunting task to say the least. On average a dialysis machine will expel 240 liters of pure water to extract wastes from the blood during a single treatment whereas a normal healthy human will only expel approximately two liters of adequately concentrated waste in the form of urine a day [6]. This is one of the major complications faced by engineers, but there are other more major concerns regarded by consumers. The most prevalent concern for the consumer is whether the device would be covered by insurance. Currently, Medicare pays for approximately 80 percent of the cost for dialysis [10]. If this trend continues for the implantable renal assist device then it would make the cost bearable for most consumers. According to the developers, the device will “become eligible for insurance coverage” as soon as the device hits the market [11]. As with most implantable devices, some possible error could occur after some amount of use. If for any reason the device ceases to function properly, the device components would need to be replaced by another noninvasive surgery [11]. However, until the device is actually implanted in a patient for clinical trials it is hard to say whether the components will be easily replaceable. Future predicted by FDA The future already looks bright for the iRAD. Recently, the iRAD was approved for a more “timely and collaborative review” by the Food and Drug Administration [13]. This faster review time will allow the device to become available to the public more quickly. The researchers are currently in stage two of three in which they are improving on the design and components of the device [14]. The team has already achieved success in patients with end stage renal disease with a “room-sized external model” [14, 15]. This promising start has lead to a plan for clinical testing by 2017 [11, 13, 14]. If the iRAD is proven effective in the clinical trials, this device will help to save hundreds of thousands of lives, and help to solve a problem that has plagued multiple generations. Work Cited [1] (2013, May 12). Want a kidney? The Telegraph: Calcutta India. [Online]. Available: http://www.telegraphindia.com/1130512/jsp/7days/story_16888310.jsp#.UjvmSx Y1alJ [2] National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Heath. (2012, March 23). The Kidney’s and How They Work. [Online]. Available: http://kidney.niddk.nih.gov/kudiseases/pubs/yourkidneys/ [3] National Kidney Foundation. (2013). About Chronic Kidney Disease. [Online]. Available: http://www.kidney.org/kidneydisease/aboutckd.cfm [4] W. H. Fissell, H. D. Humes, A. J. Fleischman, and S. Roy. (2006, Dec 4). Dialysis and Nanotechnology: Now, 10 years, or Never? Blood Purification. [Online]. (25), pp. 1217. Available: http://www.karger.com/Article/Pdf/96391 [5] University of California, San Francisco. (2013). Statistics. [Online]. Available: http://pharmacy.ucsf.edu/kidney-project/need/statistics/ [6] W. H. Fissell, S. Roy, and A. Davenport. (2013 Feb 13). Achieving more frequent and longer dialysis for the majority: wearable dialysis and implantable artificial kidney devices. Kidney International. [Online]. (84), pp. 256-264. Available: http://zb5lh7ed7a.search.serialssolutions.com.libproxy.usc.edu/uschsl?sid=Entrez: PubMed&id=pmid:23407434 [7] W. H. Fissel, A. Dubnisheva, A. N. Eldridge, A. J. Fleischman, A. L. Zydney, and S. Roy. (2009, Jan 5). High-Performance Silicon Nanopore Hemofiltration Membranes. Journal of Membrane Science. [Online]. 326 (1), pp. 58-63. Available: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2607036/ [8] Cleveland Clinic. (2007) Chronic Illness and Depression. [Online]. Available: http://www.clevelandclinic.org/health/health-info/docs/2200/2282.asp [9] University of California, San Francisco. (2013). Device. [Online]. Available: http://pharmacy.ucsf.edu/kidney-project/device/ [10] National Kidney Foundation. (2013). Dialysis. [Online]. Available: http://www.kidney.org/atoz/content/dialysisinfo.cfm [11] University of California, San Francisco. (2013). Frequently asked questions by patients. [Online]. Available: http://pharmacy.ucsf.edu/kidney-project/device/faq/ [12] University of California, San Francisco. (2013). Development plan. [Online]. Available: http://pharmacy.ucsf.edu/kidney-project/device/development-plan/ [13] K. Bole and L. Cisneros. (2013, March 21). Artificial Kidney Holds Promise for Vast Majority on Dialysis. [Online]. Available: http://www.ucsf.edu/news/2013/03/13699/artificial-kidney-holds-promise-vastmajority-dialysis [14] K. Bole. (2010, Sep 2). UCSF Artificial Kidney Project Tapped for Accelerated FDA Program. [Online]. Available: http://www.ucsf.edu/news/2012/04/11836/ucsf-artificial-kidney-project-tappedaccelerated-fda-program