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