Artificial kidney

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Artificial kidney is often a synonym for hemodialysis, but may also refer to the other renal replacement therapies (with exclusion of kidney transplantation) that are in use and/or in development. This article deals mainly with bioengineered kidneys/bioartificial kidneys that are grown from renal cell lines/renal tissue.

Contents

The first successful artificial kidney was developed by Willem Kolff in the Netherlands during the early 1940s: Kolff was the first to construct a working dialyzer in 1943.

Medical uses

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. [1] 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 excess fluid. [2]

Kidney failure results in the slow accumulation of nitrogenous wastes, salts, water, and disruption of the body's normal pH balance. This failure typically 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. [3] Diabetes and high blood pressure are seen as the 2 most common causes of kidney failure. [4] Experts predict that the demand for dialysis will increase as the prevalence of diabetes increases. [5] 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. [6]

One in three American adults are at a risk for developing kidney disease. [7] Over 26 million American adults have kidney disease and most are not aware of it. [7] More than 661,000 of them have kidney failure and 468,000 are on dialysis. [7] The large population of individuals with kidney failure drives continuing advancements in the technology of artificial kidneys so that more people can have access to treatments.[ citation needed ]

Home hemodialysis has become rare because of its disadvantages. It is expensive, time-consuming and space inefficient. In 1980, 9.7% of the dialysis population was on home hemodialysis but by 1987 the proportion had dropped to 3.6%. [8]

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 among advanced countries after Japan. [5] The United States has the highest mortality rate among patients with ESRD. On average 20% of American ESRD patients die annually, which is more than twice that of Japan. [5] 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. [5] In 2001 there were only 296,000 Americans on some form of dialysis. [5] Ten years later that number increased to more than 430,000 as a result of chronic conditions developing such as diabetes and hypertension. [5]

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). [9] 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. [10] 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. [11]

Proposed solutions

Artificial kidney

Dialyser used in hemodialysis Kunstnier.JPG
Dialyser used in hemodialysis

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 patient's blood is called a dialyser, also known as an artificial kidney. 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.[ citation needed ]

Implantable artificial kidney

The implantable artificial kidney is a second project that is being co-developed by a nephrologist named William H. Fissell IV, MD, from the Vanderbilt University Medical Center with Professor Shuvo Roy from the University of California, San Francisco. Fissell and his colleagues 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 porous 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. Fissell and his research team continue to make progress and they expected the implantable artificial kidney would enter human trials by 2017. [12] [13]

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 hope of an effective wearable hemodialysis device has become realizable. Some patients already receive continuous peritoneal dialysis treatment which allows them to remain ambulatory. However, only a small portion of dialysis patients use peritoneal dialysis treatment because it requires large amounts of dialysate to be stored and disposed. A healthy individual's kidneys filter blood 24 hours/day, 168 hours/week compared to an individual with end-stage renal disease whose dialysis treatment plan is approximately 12 hours a week. The treatment results in a lower quality of life as well as a higher 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 receive dialysis continuously while maintaining a normal life. [14] [15] [16] The FDA approved the first human clinical trial in the United States for a wearable artificial kidney designed by Blood Purification Technologies Inc. The 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. [14] It is designed to run continuously on batteries, allowing patients to remain ambulatory when wearing the device, leading to a greater quality of life. The device is designed to improve other physiological aspects of the patient's health such as improved volume control, decreased hypertension and sodium retention, as well as a decreased rate of cardiovascular disease and stroke. [14] [15] [16]

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.[ citation needed ]

One experiment that took place included eight people who wore the WAK for four to eight hours. [14] 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. [14] Another outcome that took place during this experiment was that a needle connected to the WAK ended up disconnecting itself. [14] When this happened, the WAK was able to recognize this, and the blood stopped pumping. [14] When the blood stopped pumping, the needle could be reinserted without the body losing a large amount of blood. [14] 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. [17] 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. [17]

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. [14] 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. [18] 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. [18] 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. [14]

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. [19] [20] [21]

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. [22]

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.

The Kidney Project is a national research initiative that focuses on the development and testing of an implanted, freestanding bioartificial kidney. [23]

See also

Related Research Articles

<span class="mw-page-title-main">Autosomal dominant polycystic kidney disease</span> Medical condition

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common, life-threatening inherited human disorders and the most common hereditary kidney disease. It is associated with large interfamilial and intrafamilial variability, which can be explained to a large extent by its genetic heterogeneity and modifier genes. It is also the most common of the inherited cystic kidney diseases — a group of disorders with related but distinct pathogenesis, characterized by the development of renal cysts and various extrarenal manifestations, which in case of ADPKD include cysts in other organs, such as the liver, seminal vesicles, pancreas, and arachnoid membrane, as well as other abnormalities, such as intracranial aneurysms and dolichoectasias, aortic root dilatation and aneurysms, mitral valve prolapse, and abdominal wall hernias. Over 50% of patients with ADPKD eventually develop end stage kidney disease and require dialysis or kidney transplantation. ADPKD is estimated to affect at least one in every 1000 individuals worldwide, making this disease the most common inherited kidney disorder with a diagnosed prevalence of 1:2000 and incidence of 1:3000-1:8000 in a global scale.

<span class="mw-page-title-main">Kidney dialysis</span> Removal of nitrogenous waste and toxins from the body in place of or to augment the kidney

Kidney dialysis is the process of removing excess water, solutes, and toxins from the blood in people whose kidneys can no longer perform these functions naturally. This is referred to as renal replacement therapy. The first successful dialysis was performed in 1943.

<span class="mw-page-title-main">Kidney failure</span> Disease where the kidneys fail to adequately filter waste products from the blood

Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as either acute kidney failure, which develops rapidly and may resolve; and chronic kidney failure, which develops slowly and can often be irreversible. Symptoms may include leg swelling, feeling tired, vomiting, loss of appetite, and confusion. Complications of acute and chronic failure include uremia, hyperkalaemia, and volume overload. Complications of chronic failure also include heart disease, high blood pressure, and anaemia.

<span class="mw-page-title-main">Uremia</span> Type of kidney disease, urea in the blood

Uremia is the term for high levels of urea in the blood. Urea is one of the primary components of urine. It can be defined as an excess in the blood of amino acid and protein metabolism end products, such as urea and creatinine, which would be normally excreted in the urine. Uremic syndrome can be defined as the terminal clinical manifestation of kidney failure. It is the signs, symptoms and results from laboratory tests which result from inadequate excretory, regulatory, and endocrine function of the kidneys. Both uremia and uremic syndrome have been used interchangeably to denote a very high plasma urea concentration that is the result of renal failure. The former denotation will be used for the rest of the article.

<span class="mw-page-title-main">Hemodialysis</span> Medical procedure for purifying blood

Hemodialysis, also spelled haemodialysis, or simply dialysis, is a process of purifying the blood of a person whose kidneys are not working normally. This type of dialysis achieves the extracorporeal removal of waste products such as creatinine and urea and free water from the blood when the kidneys are in a state of kidney failure. Hemodialysis is one of three renal replacement therapies. An alternative method for extracorporeal separation of blood components such as plasma or cells is apheresis.

<span class="mw-page-title-main">Peritoneal dialysis</span> Type of dialysis

Peritoneal dialysis (PD) is a type of dialysis which uses the peritoneum in a person's abdomen as the membrane through which fluid and dissolved substances are exchanged with the blood. It is used to remove excess fluid, correct electrolyte problems, and remove toxins in those with kidney failure. Peritoneal dialysis has better outcomes than hemodialysis during the first couple of years. Other benefits include greater flexibility and better tolerability in those with significant heart disease.

<span class="mw-page-title-main">Diabetic nephropathy</span> Chronic loss of kidney function

Diabetic nephropathy, also known as diabetic kidney disease, is the chronic loss of kidney function occurring in those with diabetes mellitus. Diabetic nephropathy is the leading causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD) globally. The triad of protein leaking into the urine, rising blood pressure with hypertension and then falling renal function is common to many forms of CKD. Protein loss in the urine due to damage of the glomeruli may become massive, and cause a low serum albumin with resulting generalized body swelling (edema) so called nephrotic syndrome. Likewise, the estimated glomerular filtration rate (eGFR) may progressively fall from a normal of over 90 ml/min/1.73m2 to less than 15, at which point the patient is said to have end-stage renal disease. It usually is slowly progressive over years.

<span class="mw-page-title-main">Home hemodialysis</span>

Home hemodialysis (HHD) is the provision of hemodialysis to purify the blood of a person whose kidneys are not working normally, in their own home. One advantage to doing dialysis at home is that it can be done more frequently and slowly, which reduces the "washed out" feeling and other symptoms caused by rapid ultrafiltration, and it can often be done at night, while the person is sleeping.

<span class="mw-page-title-main">Hepatorenal syndrome</span> Human disease

Hepatorenal syndrome is a life-threatening medical condition that consists of rapid deterioration in kidney function in individuals with cirrhosis or fulminant liver failure. HRS is usually fatal unless a liver transplant is performed, although various treatments, such as dialysis, can prevent advancement of the condition.

In medicine, Kt/V is a number used to quantify hemodialysis and peritoneal dialysis treatment adequacy.

<span class="mw-page-title-main">Hemofiltration</span>

Hemofiltration, also haemofiltration, is a renal replacement therapy which is used in the intensive care setting. It is usually used to treat acute kidney injury (AKI), but may be of benefit in multiple organ dysfunction syndrome or sepsis. During hemofiltration, a patient's blood is passed through a set of tubing via a machine to a semipermeable membrane where waste products and water are removed by convection. Replacement fluid is added and the blood is returned to the patient.

Renal replacement therapy (RRT) is therapy that replaces the normal blood-filtering function of the kidneys. It is used when the kidneys are not working well, which is called kidney failure and includes acute kidney injury and chronic kidney disease. Renal replacement therapy includes dialysis, hemofiltration, and hemodiafiltration, which are various ways of filtration of blood with or without machines. Renal replacement therapy also includes kidney transplantation, which is the ultimate form of replacement in that the old kidney is replaced by a donor kidney.

<span class="mw-page-title-main">Ultrafiltration (kidney)</span> Filtration by a semi-permeable membrane

In renal physiology, ultrafiltration occurs at the barrier between the blood and the filtrate in the glomerular capsule in the kidneys. As in nonbiological examples of ultrafiltration, pressure and concentration gradients lead to a separation through a semipermeable membrane. The Bowman's capsule contains a dense capillary network called the glomerulus. Blood flows into these capillaries through the afferent arterioles and leaves through the efferent arterioles.

Hemoperfusion or hæmoperfusion is a method of filtering the blood extracorporeally to remove a toxin. As with other extracorporeal methods, such as hemodialysis (HD), hemofiltration (HF), and hemodiafiltration (HDF), the blood travels from the patient into a machine, gets filtered, and then travels back into the patient, typically by venovenous access.

<span class="mw-page-title-main">Northwest Kidney Centers</span>

Northwest Kidney Centers is a regional, not-for-profit community-based provider of kidney dialysis, public health education, and research into the causes and treatments of chronic kidney disease. Established in Seattle in 1962, it was the world's first out-of-hospital dialysis provider. It offers dialysis throughout the greater Seattle area in 20 free-standing clinics, eight hospitals and its home dialysis program. It opened its first clinic in Everett in 2020, the organization's first in Snohomish county.

Nathan W. Levin is an American physician and founder of the Renal Research Institute, LLC., a research institute dedicated to improving the outcomes of patients with kidney disease, particularly those requiring dialysis. Levin is one of the most prominent and renowned figures in clinical nephrology as well as nephrology research. He has authored multiple book chapters and over 350 peer-reviewed publications, including articles in leading journals such as Nature, the New England Journal of Medicine, and The Lancet.

A liver support system or diachysis is a type of therapeutic device to assist in performing the functions of the liver. Such systems focus either on removing the accumulating toxins, or providing additional replacement of the metabolic functions of the liver through the inclusion of hepatocytes to the device. This system is in trial to help people with acute liver failure (ALF) or acute-on-chronic liver failure.

<span class="mw-page-title-main">Rockwell Medical</span>

Rockwell Medical Inc. is a company based in Wixom, United States of Michigan and founded in the year of 1996.This company works on the development and commercialization of treatments against diseases such as end-stage renal disease (ESRD) and chronic kidney disease (CKD).

<span class="mw-page-title-main">Epstein syndrome</span> Medical condition

Epstein syndrome is a rare genetic disease characterized by a mutation in the MYH9 gene in nonmuscle myosin. This disease affects the patient's renal system and can result in kidney failure. Epstein Syndrome was first discovered in 1972 when two families had similar symptoms to Alport syndrome. Epstein syndrome and other Alport-like disorders were seen to be caused by mutations in the MYH9 gene, however, Epstein syndrome differs as it was more specifically linked to a mutation on the R702 codon on the MYH9 gene. Diseases with mutations on the MYH9 gene also include May–Hegglin anomaly, Sebastian syndrome and Fechtner syndrome.

<span class="mw-page-title-main">Amira Abdelrasoul</span> Canadian researcher and professor

Amira Abdelrasoul is a researcher and associate professor at the Department of Chemical and Biological Engineering at the University of Saskatchewan. She is the principal investigator of the Hemodialysis Membrane Science and Nanotechnology Research Centre at the University of Saskatchewan. She is also a membrane technology leader in Canada, and her interdisciplinary research program focuses on solving existing hemodialysis system problems.

References

  1. "Kidney Anatomy: Overview, Gross Anatomy, Microscopic Anatomy". 2017-08-29.{{cite journal}}: Cite journal requires |journal= (help)
  2. "The Kidneys and How They Work". www.niddk.nih.gov. Retrieved 2015-11-30.
  3. "Kidney Overview". WebMD. Retrieved 2015-12-02.
  4. "Key Points: About Dialysis For Kidney Failure". www.kidney.org. National Kidney Foundation. 2016.
  5. 1 2 3 4 5 6 Johnson, Steven (2014-10-11). "Dialysis Demand Strong as Kidney Disease Grows". www.modernhealthcare.com. Modern Healthcare.
  6. Bywaters EGL, Beall D (1941). "Crush injuries with impairment of renal function". British Medical Journal. 1 (4185): 427–32. doi:10.1136/bmj.1.4185.427. PMC   2161734 . PMID   20783577.
  7. 1 2 3 "Fast Facts". The National Kidney Foundation. National Kidney Foundation. 2014-08-12. Retrieved 2016-11-13 via kidney.org.
  8. Twardowski, Zbylut J. (Aug 9, 1994). "Artificial kidney for frequent (daily) Hemodialysis". United States Patent.
  9. Fissell WH, Humes HD, Fleischman AJ, Roy S (2007). "Dialysis and Nanotechnology: Now, 10 years, or Never?". Blood Purification. 25 (1): 12–17. doi:10.1159/000096391. PMID   17170531. S2CID   42050968.
  10. Lindsay RM, Le itch R, Heidenham AP, Kortas C (2003). "The London daily/nocturnal Hemodialysis study: Study design, morbidity, and mortality results". Am J Kidney Dis. 42 Supp 1 (1 Suppl): S5–S12. doi:10.1016/S0272-6386(03)00531-6. PMID   12830437.
  11. Fissell W, Manley S, Westover A, Humes HD, Fleischman AJ, Roy S (2006). "Differentiated Growth of Human Renal Tubule Cells on Thin-Film and Nanostructured Materials". ASAIO Journal. 52 (3): 221–227. doi: 10.1097/01.mat.0000205228.30516.9c . PMID   16760708. S2CID   9494223.
  12. "Implantable artificial kidney project making progress - Nephrology News & Issues". Nephrology News & Issues. 2016-02-25. Retrieved 2016-12-07.
  13. "World's First Implantable Artificial Kidney Could Enter Human Trials By 2017". Med Device Online. Retrieved 2016-12-07.
  14. 1 2 3 4 5 6 7 8 9 10 Ronco, Claudio; Davenport, Andrew; Gura, Victor (2008-07-01). "Toward the wearable artificial kidney". Hemodialysis International. 12: S40–S47. doi:10.1111/j.1542-4758.2008.00295.x. ISSN   1542-4758. PMID   18638240. S2CID   5721553.
  15. 1 2 Gura, Victor; Rivara, Matthew B.; Bieber, Scott; Munshi, Raj; Smith, Nancy Colobong; Linke, Lori; Kundzins, John; Beizai, Masoud; Ezon, Carlos (2016). "A wearable artificial kidney for patients with end-stage renal disease". JCI Insight. 1 (8). doi:10.1172/jci.insight.86397. ISSN   2379-3708. PMC   4936831 . PMID   27398407.
  16. 1 2 Gura, Victor; Macy, Alexandra S.; Beizai, Masoud; Ezon, Carlos; Golper, Thomas A. (2016-12-07). "Technical Breakthroughs in the Wearable Artificial Kidney (WAK)". Clinical Journal of the American Society of Nephrology. 4 (9): 1441–1448. doi:10.2215/CJN.02790409. ISSN   1555-9041. PMC   2736696 . PMID   19696219.
  17. 1 2 Markovic, M.; Rapin, M.; Correvon, M.; Perriard, Y. (2013-09-01). "Design and Optimization of A Blood Pump for A Wearable Artificial Kidney Device". IEEE Transactions on Industry Applications. 49 (5): 2053–2060. doi:10.1109/TIA.2013.2260851. ISSN   0093-9994. S2CID   16399324.
  18. 1 2 Kim, Jeong Chul; Garzotto, Francesco; Nalesso, Federico; Cruz, Dinna; Kim, Ji Hyun; Kang, Eungtaek; Kim, Hee Chan; Ronco, Claudio (2011). "A wearable artificial kidney: technical requirements and potential solutions". Expert Review of Medical Devices. 8 (5): 567–579. doi:10.1586/erd.11.33. PMID   22026622. S2CID   38028816.
  19. Saito A, Aung T, Sekiguchi K, Sato Y, Vu D, Inagaki M, Kanai G, Tanaka R, Suzuki H, Kakuta T (2006). "Present status and perspectives of bioartificial kidneys". J Artif Organs. 9 (3): 130–5. doi:10.1007/s10047-006-0336-1. PMID   16998696. S2CID   19908009.
  20. Saito A, Aung T, Sekiguchi K, Sato Y (2006). "Present status and perspective of the development of a bioartificial kidney for chronic renal failure patients". Ther Apher Dial. 10 (4): 342–7. doi:10.1111/j.1744-9987.2006.00387.x. PMID   16911187. S2CID   6460237.
  21. Wang P, Takezawa T (2005). "Reconstruction of renal glomerular tissue using collagen vitrigel scaffold". J Biosci Bioeng. 99 (6): 529–40. doi:10.1263/jbb.99.529. PMID   16233828.
  22. Fissell W, Fleischman AJ, Roy S, Humes HD (2007). "Development of continuous implantable renal replacement: past and future". Translational Research. 150 (6): 327–336. doi:10.1016/j.trsl.2007.06.001. PMID   18022594.
  23. "Home | The Kidney Project | UCSF". pharm.ucsf.edu. Retrieved 2018-12-11.