The Role of Sugar in Polycystic Kidney Disease

A study of kidney organoids in a novel lab setting could have implications for the treatment of polycystic kidney disease (PKD), an incurable condition affecting over 12 million people worldwide. One important finding of the study is that sugar appears to play a role in the production of the fluid-filled cysts that are characteristic of PKD. In people, these cysts grow big enough to impair kidney function and ultimately cause the organs to fail. Ultimately, the patient has to go in for dialysis therapy or transplant (1^✔ ✔Trusted Source
Glucose absorption drives cystogenesis in a human organoid-on-chip model of polycystic kidney disease

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Effect of Sugar on Kidneys

Sugar uptake is something that kidneys do all the time. Researchers found that increasing the levels of sugar in dish-cultures caused cysts to swell. And when they employed drugs known to block sugar absorption in the kidneys, it blocked this swelling. It relates less to blood sugar level and more to how kidney cells take in sugar — which in this process seemed to go berserk and give rise to cysts.

For years researchers have studied PKD in organoids grown from pluripotent stem cells. Organoids resemble miniature kidneys: They contain filtering cells connected to tubes and can respond to infection and therapeutics in ways that parallel the responses of kidneys in people.

Although researchers can grow organoids that give rise to PKD cysts, the mechanisms of those cysts’ formation are not yet understood. This investigation focused on how the flow of fluid within the kidney contributes to PKD.

To accomplish this, scientists developed a new technique that combines a kidney organoid with a microfluidic chip. This allowed water, sugar, amino acids, and other nutrients to flow over organoids that had been genetically modified to mimic PKD.

Researchers were expecting the PKD cysts in the organoids to get worse under flow because the disease is associated with the physiological flow rates that they were exploring. The interesting part was that the process of cyst-swelling involved absorption: the intake of fluid inward through cells from outside the cyst. That’s the opposite of what is commonly thought, which is that cysts form by pushing fluid outward through cells. It’s a whole new way of thinking about cyst formation.

In the chips, the researchers observed that the cells lining the walls of the PKD cysts faced outward as they stretched and swelled, such that the tops of the cells were on the outside of the cysts. This inverted arrangement - these cells would be facing inward in living kidneys - suggests that cysts grow by pulling in sugar-rich fluid, not by secreting the liquid.

Potential for Treatment of Polycystic Kidney Disease

The observation gives researchers more information about how cysts form in organoids, a finding that will have to be tested further in vivo. As well, the fact that sugar levels drive cyst development points to new potential therapeutic options.

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The results of the experiment are significant because there is a whole class of molecules that block sugar uptake in the kidneys and are attractive therapeutics for a number of conditions. They haven’t been tested yet, but researchers view this as a proof-of-concept that these drugs could potentially help PKD patients.

Polycystic kidney disease (PKD) is a genetic disorder that causes many fluid-filled cysts to grow in the kidneys. Unlike the usually harmless simple kidney cysts that can form in the kidneys later in life, PKD cysts can change the shape of the kidneys, including making them much larger.

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PKD is a form of chronic kidney disease (CKD) that reduces kidney function and may lead to kidney failure. PKD also can cause other complications, such as high blood pressure, cysts in the liver, and problems with blood vessels in the brain and heart (2^✔ ✔Trusted Source
Polycystic kidney disease

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References:

1. Glucose absorption drives cystogenesis in a human organoid-on-chip model of polycystic kidney disease - (https://www.nature.com/articles/s41467-022-35537-2)
2. Polycystic kidney disease - (https://www.mayoclinic.org/diseases-conditions/polycystic-kidney-disease/symptoms-causes/syc-20352820)

Source-Medindia