Photo Caption: An immunofluorescence micrograph of kidney distal convoluted tubules treated with a low potassium diet. The magenta stain is sodium-chloride symporter (NCC), and the green structures are WNK bodies. (Photo provided by Cary Boyd-Shiwarski and Arohan Subramanya)
By Kat Procyk
New research from the University of Pittsburgh School of Medicine found that our kidneys are quick to sound the alarm when they detect a dip in potassium levels—even if those levels are in the normal range according to medical standards.
One of the main functions of the kidney is to maintain blood potassium levels and, to do so, it has its own emergency response system. The distal convoluted tubule, a part of the kidney, acts as a vigilant operator standing by a big red “Alert!” button. The moment it senses even the slightest drop in potassium levels, it springs into action by absorbing sodium chloride (salt). This salt absorption process prevents potassium from being excreted in the urine, helping the body conserve potassium.
The red alert button activates a protein called the sodium-chloride symporter (NCC), which absorbs salt back into the body, but NCC doesn’t act alone. It gets switched on by a team of enzymes known as With-No-Lysine (WNK) kinases.
When potassium levels fall too low, a special version of one of these enzymes, KS-WNK1, acts as a team leader. It organizes the rest of the WNK kinases into tightly packed units called WNK bodies, biomolecular condensates that act like mini command centers inside the cell. These structures help coordinate the salt-saving response quickly and efficiently, keeping the body's balance in check.
“This suggests that even though potassium is within low-normal limits, the kidney is still stressed,” said Arohan Subramanya, associate professor of medicine and of cell biology, School of Medicine. “The kidney is thinking that potassium concentrations are low and is trying to hyper-absorb salt because of it. We think this process may have an important role in cardiovascular disease, high blood pressure and stroke.”
The researchers found that when KS-WNK1 was deleted from a model, low potassium stress was more severe in females, while high potassium stress was more severe in males, suggesting sex-specific differences. Notably, WNK bodies also differed between males and females, including in appearance, size and location. However, researchers are still unsure what the full implications are of those differences.
“One of the intriguing broader implications of our findings is that they support the idea that biomolecular condensates can regulate biological processes in a sex-specific manner,” said Cary Boyd-Shiwarski, assistant professor of medicine, School of Medicine. “Additionally, our study sheds light on a key reason why females tend to activate salt transport—specifically salt reabsorption in this segment of the kidney—more robustly than males.”
These findings also suggest that therapeutic implications in the future are more simplistic than medications: Eat more potassium.
“It’s the diet we all know we should eat—whole food, plant-based, rich in fruits, vegetables and beans,” Boyd-Shiwarski said. “It just makes sense. It’s how we evolved, and it keeps our kidneys happy. Clinically, this work suggests we might manage blood pressure not just by cutting salt, but by monitoring and adjusting potassium levels—even with a simple supplement, which could be easier for some than strict sodium restriction.”
This study is a continuation of the team’s serendipitous findings published by Cell in 2022, where they unveiled how WNK kinases form biomolecular condensates that help cell volume return to normal after being exposed to an outside stressor—like salt—through a process called phase separation.
“Once we made that discovery, our next goal was to understand how WNKs, their tendency to form condensates and human health were linked,” Subramanya said. “This finding shows how the kidney uses WNK bodies to preserve an emergency supply of potassium during times of stress, at the expense of increasing salt-sensitive blood pressure.”
The paper, “Kidney-specific WNK1 amplifies kidney tubule responsiveness to potassium via WNK body condensates,” was published by the Journal of Clinical Investigation on June 10, 2025.