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March 13, 2019updated 26 Jun 2019 10:47am

World Kidney Day: transforming kidney disease treatment with stem cells

Dialysis and kidney transplants remain the standard of care for kidney disease, despite the prevalence of the condition and the impracticality of these two therapeutic options. Stem cells are opening up new treatment options in a range of disorders, but how could they help to improve treatment of kidney disease?

By Allie Nawrat

Chronic kidney disease (CKD) is a general term for a situation where someone’s kidneys do not work as they should. According to Kidney Care UK, approximately three million people in the UK have CKD and there are 40-45,000 premature deaths due to the condition. Its global prevalence has been estimated by the Society for Academic Primary Care at 11-13%.

Dysfunctional kidneys can lead to serious complications, such as high blood pressure, nerve damage and anaemia, as well as increasing the likelihood of developing acute kidney injury (AKI) and kidney failure, which is also known as stage five or end-stage CKD.

Around 61,000 people in the UK are being treated for kidney failure and approximately 10,000 deaths each year are associated with AKI, according to Kidney Care UK figures.

World Kidney Day aims to improve awareness of the importance of the kidneys to a person’s general health, as well as work to reduce the impact and burden of kidney disease globally.

It is a joint initiative by the International Society of Nephrology and the International Federation of Kidney Foundations, and was launched for the first time in 2006.

The primary treatment options for CKD are medications to control symptoms, dialysis and kidney transplants; none of these are cures for kidney disease.

Dialysis performs the kidney’s functions of removing waste, salt and excess waste to prevent toxic build and maintains a safe level of certain chemicals in the blood. It is a huge burden on both patients and healthcare systems.

Transplants provide a better quality and length of life for CKD patients than dialysis, but finding suitable donor organs is extremely competitive. According to Kidney Care UK, over 3,000 kidney transplants take place every year, but more than 5,000 patients remain waiting on the donor list in the UK. The average wait is three years and every day one patient dies waiting for a kidney transplant.

How can stem cells help treat kidney disease?

Stem cell-based therapies are potentially transformative in the treatment of kidney disease as they resolve the issue of there being an insufficient number of donor kidneys, reduce the likelihood of organs being rejected following transplants and reduce patient’s reliance on burdensome dialysis treatment.

There are plenty of obstacles blocking wider use of stem cells to treat any condition and kidneys pose particular constraints on research and development because they contain complex structures and a diverse range of cells.

Despite the roadblocks, researchers continue to investigate and test various ways in which stem cells can be used to improve how kidney diseases are treated.

Researching on patient cell-derived kidney organoids

Scientists in Utrecht, the Netherlands, have successfully grown kidney organoids from adult patients’ pluripotent urine stem cells.

The mini-kidneys have similar cell structures to kidneys, therefore allowing researchers to use them to “model various disorders: hereditary kidney diseases, infections and cancer,” according to Dr Hans Celvers, professor of Molecular Genetics at Utrecht University and the University Medical Centre (UMC) Utrecht, as well as group leader at the Hubrecht Institute.

“This allows us to study in detail what exactly is going wrong…[and] helps us to understand the workings of healthy kidneys better, and hopefully, in the future, we will be able to develop treatments for kidney disorders.”

The researchers noted specifically these organoids could be used to find an effective treatment against viral infections often contracted by patients following a kidney transplant. Professor of Experimental Nephrology at UMC Utrecht Marianne Verhaar said: “In the lab, we can give a mini kidney a viral infection which some patients contract following a kidney transplant. We can then establish whether this infection can be cured using a specific drug.”

Creating a bioengineered vein to improve dialysis

California’s Stem Cell Agency has funded Phase III clinical trials into regenerative medical technology company Humacyte’s human acellular vessel (HAV) Humacyl to be used during the most common form of dialysis, haemodialysis, for patients with end-stage kidney failure.

Humacyl is implanted into the patient’s arm and used to carry blood to and from the patient’s body during dialysis. The study compares Humacyte’s HAV to synthetic grafts made from expanded polytetrafluoroethylene (ePTFE).

The HAV is created from donor smooth muscle cells placed on a tubular scaffold composed of biodegradable structure material; the product is decelluralised,meaning the product can be used for any patient at any time.

In vitro tissue cells form a biologic 3D scaffold matrix and once implanted patient stem cells start to naturally populate the vein, thus making it part of the patient’s own body, preventing an inflammatory and immune response from the patient.

The success of the trials into Humacyl in end-stage kidney failure has led Humacyte to consider HAVs as potential transformative solutions for other conditions, including peripheral arterial disease and vascular trauma.

Exploiting the regenerative properties of certain cells

Additionally, a team at the University of Turin, Italy, discovered some cells in the kidneys with regenerative abilities, all expressed through molecule called CD133. So the team set about discovering the precise role of this molecule in renal repair.

They subjected CD133-expressive cells with chemotherapy cisplatin, which is known to cause damage to kidneys. By isolating RNA they found that the cells lost their CD133 signature and acquired regenerative genes, then in the recovery phase CD133 was reacquired.

Also, they discovered a lack of CD133 limited the proliferation of cells and directly correlated with the deregulation of the Wnt signalling pathway; research has shown that the Wnt signalling pathway is involved in the development of various kidney disorders.

According to the California Stem Cell Agency, this opens up new areas for research, which could include infusions of CD133 to help patients repair their damaged kidneys.

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