Big steps in protecting the kidney filter
With funding from Kidney Research UK, researchers have tested a new treatment and early indications suggest that it protects the kidney filter from injury, maintaining kidney function.
The kidneys remove waste from the bloodstream, preventing it from passing into urine. When the kidneys don’t work properly, the filter becomes leaky and proteins which should be kept in the bloodstream, are lost in the urine. This is known as proteinuria, an early sign of kidney disease and can increase the risk of stroke and cardiovascular problems.
Podocyte cells cover the surface of the capillaries of the glomerulus, the filtering unit of the kidneys. They play an important role in preventing proteins from entering the urine and are supported by a “backbone” known as the cytoskeleton which helps to maintain their shape. When the shape of podocytes is altered, filtration is affected, and this can be harmful to the body. The podocyte cytoskeleton must therefore be protected against injury so that the podocytes can maintain their shape and continue to help the kidneys work properly.
Podocytes must be protected
Dr Elisa Vasilopoulou from the Royal Veterinary College, and her team set out to find out how to protect the cytoskeleton, working in collaboration with researchers at University College London.
From results of previous research, Elisa and team knew that a protein, thymosin β4 (TB4) helps to maintain the cytoskeleton of podocytes. They also knew that removing TB4 disrupts the podocyte cytoskeleton, showing a relationship between the levels of TB4 and podocyte injury. The team then thought that if they increase the levels of TB4 in the blood stream, the podocyte cytoskeleton might be protected and so they tested this in the lab using mice.
A drug called Adriamycin was used to mimic kidney disease and they found that using TB4 to treat podocytes prevented damage to the podocyte cytoskeleton caused by the drug. This was an important finding because it meant that TB4 could help to protect the podocytes from injury and maintain the kidney's ability to filter blood effectively, preventing diseases such as proteinuria. To test this, they then used gene therapy, (which involves changing the genes within a cell to treat disease), to increase the levels of TB4 in the mouse circulation. They saw that increasing the TB4 levels prevents podocyte loss, maintaining the kidney's ability to filter effectively.
First author on the paper, Dr Will Mason from University College London said: “The podocyte cytoskeleton is central to many important cellular processes. TB4 directly protecting the podocyte cytoskeleton provides real promise that this work may impact the future of the patients who suffer with chronic kidney disease (CKD)”
Elisa said: “Protecting the cytoskeleton of podocytes is key to maintain the function of these specialised cells. TB4 treatment could be a promising new therapy for kidney diseases that involve podocyte injury. “Future work will assess whether TB4 can repair injured podocytes and improve kidney filtration in mice with established proteinuria, so that we take steps to translate this work in the clinical setting for patients with CKD”
Dr Aisling McMahon, Kidney Research UK’s executive director of research, innovation and policy said: “Dr Elisa and her team’s use of gene therapy to increase the levels of TB4 in circulation is a prime example of how scientific ingenuity can be used to discover new ways of treating kidney disease. The latest development in mice is an important step forward and we hope that the team can replicate these initially promising results in humans in the near future”
Read the full paper here
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