Discovery could spare patients from kidney transplant

Illustrative photo of an operating theater (photo credit: Nati Shohat/Flash90)

Researchers in Israel and the US have discovered that, contrary to popular medical opinion, the human kidney is able to regenerate itself. Until now, scientists had believed that the liver is the only human organ that can regenerate itself.

A new study by researchers at Sheba Medical Center, Tel Aviv University, and Stanford University shows, for the first time, how the kidney pulls off this trick. Using genetically modified mice, the researchers were able to trace cell growth in the kidney, which reconstituted itself in the proper array of tubes and ducts.

According to US health officials, one in 10 American adults — more than 20 million people — have some level of chronic kidney disease (CKD), which results in reduced kidney function over time.

Kidney disease primarily affects older people, and the problem is growing, according to the National Institutes of Health: CKD now affects more than one-quarter of Americans over the age of 60. At any one time, over 120,000 people are on a waiting list for a kidney transplant, and about 20 people a day die before a suitable donor can be found.

The study is revolutionary in a number of ways, according to Dr. Benjamin Dekel of TAU’s Sackler School of Medicine and the Sheba Medical Center — above all, for what it could mean for the kidney-transplant issue. “Very little is known, even now, about the way our internal organs function at the single-cell level. This study flips the paradigm that kidney cells are static. In fact, kidney cells are continuously growing, all the time,” he explained. If the regeneration process could be speeded up, said Dekel, it could obviate the need for a kidney transplant in most CKD sufferers.

The researchers used a “rainbow mouse” model — genetically developed to give off fluorescent signals in cells — which allowed them to follow the fate of the cells. Using the mouse, the team was able to pinpoint a specific molecule responsible for renal cellular growth, which is known as the “WNT signal.”

Once activated in specific precursor cells in each kidney segment, the WNT signal results in robust renal cellular growth and generation of long branches of cells. To boot, the trio found that the growth was sectional and multidirectional, with each of the nephrons (the filtering tubes that are the basic unit of the kidney) growing at its own pace, complete with its own network of associated tubules, capillaries, and other components.

According to Dr. Dekel: “No one had ever used a rainbow-mouse model to monitor the development of kidney cells. It was exciting to use these genetic tricks to discover that cellular growth was occurring all the time in the kidney — that, in fact, the kidney was constantly remodeling itself in a very specific model. Each part of the nephron is responsible for its own growth, each segment responsible for its own development, like a tree trunk and branches — each branch grows at a different pace and in a different direction.”

With the key to kidney cell growth now unlocked, the next stage, explained Dekel, is to develop techniques to enhance growth, with the aim of enabling a CKD patient to regenerate his kidneys without resorting to a transplant.

“This study teaches us that, in order to regenerate the entire kidney segments, different precursor cells grown outside of our bodies will have to be employed,” added the doctor. “In addition, if we were able to further activate the WNT pathway, then, in cases of disease or trauma, we could activate the phenomena for growth and really boost kidney regeneration to help patients. This is a platform for the development of new therapeutics, allowing us to follow the growth and expansion of cells following treatment.”

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