Previously unobserved pumping action of kidney cells discovered

Kidneys perform a vital function in removing waste and toxins from the blood, but how exactly cells transport that fluid through the organs has remained a mystery. Now researchers at Johns Hopkins University have investigated the mechanical forces at work and found a previously unobserved pumping action by kidney cells.

All the blood in your body passes through the kidneys dozens of times per day, flowing through tiny tubes and filtering units before the “clean” blood makes its way back out into the bloodstream. But the mechanical forces required to pull this off weren’t clear – after all, the epithelial cells lining these tubes were thought to be immobile.

"Fundamental physical laws say that you need forces to move things,” said Sean Sun, corresponding author of the new study. “In this case, the cells are not moving, but they are moving fluid. The question then becomes how do they do this?"

To investigate, the Johns Hopkins researchers modeled the organ using an artificial micro-fluidic kidney pump. In this setup, fluids pass from a microchannel, through cultured kidney epithelial cells and into a second microchannel, while the device records fluid pressure in different areas.

And sure enough, the team observed kidney epithelial cells functioning like mechanical fluid pumps. They actively generated a fluid pressure gradient, which drives the fluid in a specific direction like a common household water pump.

In follow-up experiments, the team examined how the function of these cells could change in cases of disease. They tested the same device using kidney epithelial cells from patients with autosomal dominant polycystic kidney disease (ADPKD), a disorder that causes fluid-filled cysts to form.

The diseased cells were found to pump fluid in the opposite direction to healthy cells. This changed the pressure profile of the kidney tubes and altered their shape, which could play a major role in the development of the cysts.

Next, the researchers tested a drug called Tolvaptan, which is used to slow progression of ADPKD, in the microfluidic device to examine how it worked. They found that the drug causes the cells to lower their pumping flux and pressure gradients, which slows the development of the cysts.

The team says the discovery could unlock new potential drugs or treatments, while the device could find use as a screening tool for ADPKD and other diseases, in the kidney and other organs.

The research was published in the journal Nature Communications.

Source: Johns Hopkins University