PKD: Stem Cell Therapy, Artificial Kidney Development

Living with PKD

From Check BioTech

Polycystic Kidney Disease And Stem Cell Therapy

Polycystic kidney disease is a genetic disorder in which cysts form in the kidneys, causing the organ to enlarge, and gradually impairing its function as the disease progresses. The renal tubule of usually becomes irregularly and abnormally shaped, which eventually leads to the formation of the cysts. These cysts may start developing as early as when the individual was still in-utero, to when the affected individual becomes an adult. These cysts can be defined as tubules that have lost their functions but becomes filled with fluid. This size differs from people to people, but they usually range from small to large sizes. The cyst grows, and also goes further to impair the function of the next tubule, destroying it and turning it into a cyst too. Genetics has been identified as the cause of this disease. According to studies, these defected genes induces the production of an abnormal protein. The protein has been implicated as the reason behind the malformation and damage of the renal tubules, that would eventually become cysts. There are two types of Polycystic kidney disease. This includes the Autosomal polycystic kidney disease, and the autosomal recessive polycystic kidney disease.

This disease can be diagnosed based on the presenting symptoms. For example, patients would usually complain of a groin pain, colored urine, enlarged kidney or a history of a family member that had the disease. The diagnosis can be confirmed by undergoing a Computer tomography scan. Some of the complications of this disease are infections and hypertension. Treatment options are transplantation and other forms of symptomatic therapy.Adipose extracted stem cells have been shown to be effective in treating this disease.

What are the signs and symptoms of Polycystic kidney disease?

Polycystic kidney disease presents with various symptoms in different people. Some of the symptoms of this disease are;

1. Hypertension: This is one of the most common symptoms of this disease. Affected individuals usually have a high blood arterial pressure.
2. Headache
3. Pain: Patients might feel pain in their groin. This pain can sometimes become very severe.
4. Hematuria: Hematuria is a condition in which the patient’s urine contains blood. This is mostly as a result of the impairment of the renal tubules.
5. Kidney stones: The impaired function of the kidney tubules facilitate the development of renal stones. These stones if less than 3mm can pass on their own without the use of any medication. However, a kidney stone that is big sized might require procedures such as percutaneous nephrostomy.
6. Renal failure: This eventually happens when the disease is not well managed. This can also become worse if ignored.
7. Swelling of the abdomen: The abdomen usually feels bigger. This can be attributed to the enlarged kidneys.

What’s the cause of polycystic kidney disease?

As said earlier, this disease is caused by a defected gene that induces the production of an abnormal protein. This protein generally impairs the development of the kidney tubule. There are two types of this disease, and these are autosomal dominant polycystic kidney disease and autosomal recessive polycystic kidney disease. The cause of the disease is specific to each of them.

Autosomal dominant polycystic kidney disease: This is the most predominant type of the polycystic diseases. Studies have shown that about one in ten cases of patients on dialysis were initially diagnosed and treated for this disease. This disease is more common in people between the ages of thirty and forty. However, children do get affected by this disease. This disease is autosomal dominant, which implies that only a parent is needed to have this disease, for the children to get affected. A child has a fifty percent chance of having the disease even if one of the parents has the disease.
Autosomal recessive polycystic kidney disease: This disease is far less common when compared to autosomal recessive polycystic kidney disease. The signs and symptoms don’t usually present early until the child grows into adolescence. This disease is generally more predominant in children. It’s an autosomal recessive disease, so both parents must have the abnormal genes for the child to have a chance of having the disease.

What are the complications of Polycystic kidney disease?

Below are some of the complications of this disease;

1. Hypertension: This occurs due to as a result of the cysts in the kidney. This disease can progress to more severe complications if left untreated. Examples of further complications that can arise from this disease are renal failure, cardiac-related diseases and stroke.
2. Impairment of the renal system: The gradual loss of the functions of the kidney is one of the most prominent symptoms of this disease. According to statistics, more than half of the people affected with this disease usually presents with renal failure by the time they attain the age of sixty. Some of the symptoms of an impaired kidney include the inability of the kidney to eliminate toxic materials from the body.
3. Preeclampsia: Polycystic kidney disease increases the risk of which pregnant women can develop preeclampsia. This is a condition in which pregnant women experience proteinuria and hypertension during pregnancy.
4. Cardiac–related diseases.
5. Gastrointestinal problems
6. Long-term pains: Pain is a symptom that is common to most people affected by this disease. It often affects the lower part of the back and side of the body. Patients might also experience an infection of the urinary tract.

How is polycystic kidney disease currently treated?

There are no FDA approved treatments for this disease yet. However, patients are usually given symptomatic treatments. The purpose of these treatments is generally to reduce the progression of this disease and to treat the symptoms. Anti-hypertensive medications are usually given to treat high blood pressure, and analgesics are given to reduce the pain. In addition, antibiotics are administered to treat any infection that might occur as a result of the disease. In severe conditions, dialysis might be needed to maintain the functions of the kidney.

Stem cell therapy of Polycystic diseases

Stem cells are unique cells that can proliferate, regenerate, repair and replace damaged or injured cells and tissues of the body. This is what makes the therapy effective in the treatment of this disease. Stem cells extracted from the adipose tissues are usually used for this purpose. They are extracted from the patient and re-transplanted to the patient to induce other cells to repair the damaged part of the kidney.

Artificial Kidney Development

From National Institutes of Health, National Institute of BioMedical Imaging and BioEngineering

Artificial Kidney Development Advances, Thanks to Collaboration by NIBIB Quantum Grantees

Computer simulation addresses the problem of blood clotting

Creating an artificial implantable kidney would be an epic advance in medicine and could address a chronic shortage of donor kidneys needed for transplant. Researchers have been at this quest for the past 15 years and keep coming upon one extremely knotty problem: how to keep the blood flowing smoothly through the artificial device without clotting. In such devices, as blood platelets respond to mechanical forces, they have a natural tendency to clot, causing a device malfunction.

To surmount this problem, recipients of Quantum Awards from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) combined rare expertise in artificial kidney development and in computer simulation of blood flow, in a study in the Jan. 16, 2018, advance online issue of the Journal of Biomechanics.

While dialysis saves thousands, if not millions, of lives each year, it is not an ideal solution for kidney disease. Instead of continuous blood filtration, which keeps blood chemistry within a healthy range, dialysis results in ultra-cleansed and nutrient-depleted blood, which becomes gradually more toxic until the following dialysis treatment.

An artificial kidney would provide the benefit of continuous blood filtration. It would reduce kidney disease illness and increase the quality of life for patients. While researchers have made progress on wearable models, to make the device implantable—driven by the body’s own blood flows—the clotting problem would need to be resolved.

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What kidneys do—

Kidneys extract toxins from the blood and maintain fluid balance in the body by urine excretion. They also make hormones to regulate blood pressure, promote red-cell production, and support bone health.

When kidneys fail—

Kidney disease can cause kidneys to fail and toxins to build up in the blood. Kidney failure affects more than 660,000 people per year in the United States and contributes to 89,000 deaths.

Some people with kidney failure are fortunate enough to receive a transplanted donor kidney. Of the 100,000 people each year on the transplant waiting list, just 18,000 receive a donor kidney. A stop-gap measure for patients under these life-threatening conditions is dialysis, a way to process the blood through an external filtration system.

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“As developers of this technology know all too well, it is especially frustrating to deal with blood clots, which can both plug up the device, making in useless, and cause dangers to other parts of the body where blood flow would be compromised,” said Rosemarie Hunziker, Director of the NIBIB program in Tissue Engineering and Regenerative Medicine. “A clot that migrates to the heart could cause a heart attack; it could cause a stroke if it travelled to the brain.”

The implantable artificial kidney—a bioengineered device that combines a high-efficiency silicon filter and a bioreactor of kidney tubule cells—has been a long-term project for study co-authors Shuvo Roy, Ph.D., University of California, San Francisco (UCSF) professor of bioengineering and therapeutic sciences, and William H. Fissell, IV, M.D., University of Vanderbilt associate professor of medicine.

The experimental device is designed to accommodate up to a liter of blood per minute, filtering it through an array of silicon membranes. The filtered fluid contains toxins, water, electrolytes, and sugars. The fluid then undergoes a second stage of processing in a bioreactor of lab-grown cells of the type normally lining the tubules of the kidney. These cells reabsorb most of the sugars, salts, and water back into the bloodstream. The remainder becomes urine that is directed to the bladder and out of the body.

Much of the technology to implement this complex process exists, some of it developed by Roy and Fissell under previous funding from the NIBIB Quantum Award program. One of the remaining challenges is for researchers to integrate the various innovations into one functional, compact—and thus implantable—device.

In the newly published work, the UCSF-Vanderbilt team collaborated with co-author Danny Bluestein, Ph.D., professor of biomedical engineering at the State University of New York, Stony Brook, who also is a Quantum Award grantee. In 2010, NIBIB awarded Bluestein’s laboratory a grant to study thromboresistance—the prevention of clotting in circulating blood. Bluestein’s group used the technique to study cardiovascular implant devices, such as artificial heart valves, as well as the device used in surgery when temporarily bypassing heart circulation.

Roy and Fissell first heard about Bluestein’s methodology, called device thrombogenicity emulation (DTE), at a 2014 meeting at NIBIB for Quantum Award grantees. The Bluestein DTE methodology quantifies flow patterns and stressors that develop during the blood flow. During Bluestein’s description of DTE, Roy and Fissell immediately saw the potential for applying his theories to their artificial kidney design. Appropriate computer simulation could shave years or even decades off the design process for the artificial kidney and produce a device with a well analyzed and tested safety profile for platelet activation and subsequent clot formation.

“Platelets become activated, and initiate blood clotting in response to the severity of stress forces, as well as to the amount of time the platelets are circulating through the device,” Bluestein said. Bluestein’s simulation methodology—first developed to numerically predict the accumulation of stress on platelets within devices that support circulation in heart failure patients—was readily adaptable to the fluid dynamics aspects of the artificial kidney.

The researchers generated simulation and optimization results for two device designs that each channel blood through the artificial kidney filter system. Through simulation, they calculated that an individual platelet may flow through the artificial kidney as many as 1,000 times, accumulating stress and increasing the tendency to clot with each pass. One design distributes blood through parallel channels that pass across multiple layers of filtering membranes. The other channels blood back and forth through a single serpentine path.

Simulation results tipped in favor of the parallel flow system, particularly with respect to the condition of blood platelets after repeated circulation within the filtration systems. However, both designs met the researchers’ predetermined criteria for the uniform flow of blood through the devices and accumulation of shear stress forces on the platelets against the walls of the device flow channels. Therefore, the researchers plan to test both implant designs in prospective experiments in pigs. Additional designs could be tested in the future.

“I am happy that they decided to adopt our methodology, so its effectiveness could be demonstrated in a very different type of device,” Bluestein said. “Blood clotting is the major clinical problem that can occur because of flow-induced stresses that exist in all these devices.”

The simulation approach has accelerated the project by saving on animal experimentation and offering a viable alternative to examine the pros and cons of different devices that contact blood. “To do that in animal studies is time consuming, expensive, and at some level you never know if it is going to work out—because animal blood is not the same as human blood,” Roy said. “We ended up taking advantage of the extensive suite of work done by Dr. Bluestein and his colleagues and applied methodologies in computational fluid dynamics to help us analyze our designs.”

Will the device have all the functions of a native kidney? “No,” Roy said. “But the goal is for it to perform the functions that are critical, and to be a device that, once implanted, will allow a patient to eat and drink freely, have mobility, better health overall, and unlike a transplant, not require immunosuppressant drugs.”

Hunziker applauded the collaboration among recipients of NIBIB Quantum Award—a program to bring new technologies to bear on big, intractable problems in medicine. “Seeing independently funded teams self-assemble to leverage their quantum innovations is extremely gratifying,” she said. “The collaboration allows the artificial kidney development to accelerate via effective predictive modeling, combined with a thorough capability to manipulate biomaterials and a deep knowledge of kidney pathophysiology.”