Mechanism of kidney damage caused by certain osmolytes uncovered

The mechanism by which certain osmolytes cause kidney damage has been uncovered by researchers in Japan.

Using rat kidney cells treated with mannitol researchers were able to show that certain kidney cells underwent a change in their skeletal structure, inducing a transformation that can lead to renal failure. They also found ways to arrest this change, suggesting new ways to avoid serious side effects.

High pressure in the eye or the cranial fluid is a symptom of serious health problems and can cause tremendous damage. In the eye, ocular hypertension can lead to glaucoma and eventually permanent vision loss. Drugs used to treat this are often diuretics and come under a class of chemicals known as osmolytes. By dispersing into the blood, they come into contact with compartments of our body with too high a pressure, drawing out fluid and reducing the pressure. This includes mannitol, a common chemical given intravenously to tackle excess pressures in both the eye and brain. However, it is known that this lifesaving treatment has some side effects, including potential acute kidney failure. Why this occurs has continued to baffle researchers.

Now, a team led by Associate Professor Naoya Sakamoto of Tokyo Metropolitan University have uncovered a key part of the mechanism by which this can occur. Using rat kidney cells, they applied a mannitol treatment and studied how it affected epithelial (skin or surface) cells in the proximal tubes, the part of the kidney said to be the most vulnerable to osmolyte treatment. Firstly, they confirmed that a transformation known as an epithelial-mesenchymal transition (EMT) occurred, effectively transforming the cells back to a primordial state where they no longer function as skin cells. For example, they stop expressing E-cadherin, a key protein that helps bind cells together. EMT is strongly associated with renal injury. Curiously, however, the same change was not seen for another osmolyte, urea. The team discovered that mannitol, which could not traverse the membrane of these cells, caused the cells themselves to shrink due to osmotic pressure, and that it was this shrinkage that caused problems.

Looking further at the structure of the cell, they found that the skeletal structure of the cells, the cytoskeleton, was significantly impacted. The cytoskeleton is a meshwork of filaments made of actin protein, and contain important assemblies known as focal adhesions which help transmit mechanical stresses and stimuli from outside the cell to the inside. These focal adhesions were found to be rearranged in the presence of mannitol, accompanied by a significant uptick in the incorporation of a particular type of actin called alpha-SMA into the filaments. The team went on to introduce an inhibitor which prevented the rearrangement of focal adhesions. It turns out that this step successfully prevents these changes in the cytoskeleton, and also prevents EMT from occurring with mannitol in the environment.

The team’s findings show that the rearrangement of focal adhesions plays a key role in EMT in proximal tubular cells and suggest a strategy to prevent it. Translated into treatments, this may lead to enhancement in the therapeutic value of common osmolytes as a lifesaving treatment.

Related Posts

Effective Ways to Run a Successful Health Awareness Campaign

6 Effective Ways to Run a Successful Health Awareness Campaign

Health centers like yours do a lot of good for their local communities. But from time to time, you might want to run a health awareness campaign to inspire healthy…

Read more
Cigarettes Are Slowly Ending Your Life

Cigarettes Are Slowly Ending Your Life – Here’s How to Stop

Smoking can be one of the quickest ways to damage your overall health. The World Health Organization states that smoking is the leading cause of preventable deaths around the world, killing…

Read more

10 Things You Can Rely On From Your Insurance Attorney

Dealing with the insurance company is really pathetic.  Especially when you are dealing with some severe injuries, things get complicated as you need to get your treatment done along with…

Read more

Inflammation of the pancreas: pain, symptoms and complications

The pain of pancreatitis manifests itself in a specific way and is a key symptom of this disease. The pain of pancreatitis manifests itself in a specific way and is…

Read more

The main causes of edema and how to treat it

Edema is the swelling caused by excess fluid trapped in the tissues of the body. It usually occurs in the feet, ankles, and legs, but it can also occur in…

Read more

Here are 7 effective ways to clean your lungs and breathe better

Techniques to clean the lungs can be beneficial for smokers, people regularly exposed to air pollution and those with chronic diseases that affect the respiratory system. Such as asthma, chronic…

Read more