THE ESSENTIAL
- Polycystic Kidney Disease (PKD) is a genetic disease characterized by the development of fluid-containing cysts in the kidneys.
- This kidney disease affects 1 in 1,000 people. This represents between 80,000 and 100,000 French people.
- The signs of polycystic kidney disease appear in adulthood. Besides cysts on the kidneys, the most common symptoms are high blood pressure, pain in the flanks, blood in the urine, and kidney stones. In advanced cases, kidney failure.
Polycystic kidney disease (PKR) is characterized by the formation of cysts on the kidneys. As they grow, they impair kidney function and ultimately cause organ failure. A team from the University of Washington School of Medicine made a key discovery while studying the disease: sugar appears to play a role in the formation of cysts.
Work carried out on in-vitro mini-kidneys
The researchers worked on kidney organoids. It is a miniature version of the organ developed from pluripotent stem cells (they can differentiate into several cell types, editor’s note). They contain filter cells connected to tubes and can respond to infections and treatments similar to the responses of human kidneys.
Seeking to understand the role of fluid flow in the kidney in disease, scientists have developed a new tool that fuses a kidney organoid with a microfluidic chip. This allowed a combination of water, sugar, amino acids and other nutrients to flow through organoids that had been genetically engineered to mimic PKD.
“We found that increasing sugar levels in the cultures caused the cysts to swell. And when we used drugs that are known to block sugar uptake in the kidneys, it blocked that swelling. But I think that’s less related to blood sugar levels and more to how kidney cells absorb sugar – which in the process seemed to spiral out of control and give rise to cysts”explained Professor Benjamin Freedman, researcher in nephrology at the school of medicine of the university of Washington.
“A whole new way of thinking regarding cyst formation”
“We expected cysts in organoids to worsen with flow because the disease is associated with the physiological flows we were exploring”, said Professor Benjamin Freedman. But, the researchers made another observation: “The process of cyst swelling involved absorption: the supply of fluid inward through the cells from outside the cyst. This is the opposite of what is commonly thought, that cysts form by pushing fluid out through the cells. This is a whole new way of thinking regarding cyst formation.”said the specialist.
The discovery that sugar levels favor the development of cysts opens the door to new therapeutic options. Indeed, there are several molecules that stop the absorption of glucose in the kidneys. However, more studies will be needed to confirm that they are effective, beneficial, and safe for patients with polycystic kidney disease.