A New Compound To Treat Autosomal Dominant Polycystic Kidney Disease (ADPKD)

What is PKD?

Polycystic kidney disease (PKD) is an inherited disorder where cysts develop in your kidneys which causes them to enlarge and stop working properly. PKD can also cause cysts to develop in the liver. These cysts normally are noncancerous and contain fluid, they also vary in size.

What is ADPKD?

Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of PKD. Although this condition is inherited, symptoms don’t usually appear until a patient is between 30-40 years of age. Genetic defaults in the cells of the kidneys cause the cysts to grow. ADPKD “affects more than 12 million people worldwide, and many patients end up needing dialysis or a kidney transplant by the time they reach their 60’s.”

A New Treatment Option

Researchers from MIT and Yale University School of Medicine have developed a compound that may significantly impact ADPKD. This compound works within the kidney cell cysts. This medication (originally developed for treating cancer) affects these damaged cells without interfering with healthy kidney cells.

Currently, the only drug available to treat ADPKD is tolvaptan. It slows the growth of the kidney cysts, but patients experience side effects such as: frequent urination, difficulty swallowing, blurred vision, thirst and seizures. 

11beta Compounds

While studying ADPKD, researchers noticed that “these compounds also induce oxidative stress by interfering with mitochondria — the organelles that generate energy for cells.” These compounds are called 11beta compounds and can disrupt or kill cells. It has been shown that 11beta compounds can suppress tumors.

Kidney cysts also experience oxidative stress because the way they function resembles a cancer cell. 11beta compounds can do the following:

• Disrupt the mitochondria’s ability to store the molecules that produce energy.
• Act as an antioxidant to neutralize any free radicals that can cause damage.
• “Tumor cells and kidney cyst cells tend to produce increased levels of free radicals because of the oxidative stress they’re under.”
• Cystic cells can not tolerate the stress and will die. Normal, healthy cells are not affected.

Researchers for ADPKD studied the compound, 11beta-dipropyl and found that it reduced the size of kidney cysts, improved kidney function and was well tolerated. “In ADPKD, as the cysts develop in the kidneys, the tissue experiences an increased inflammatory state, which eventually stimulates fibrosis and permanent scarring.” 11beta-diprophyl reduces the inflammation in the kidneys while prompting the death of cyst cells.

Conclusion

Results suggest that patients can significantly benefit from the administration of 11beta compounds once every few months or even once a year. This treatment appears to slow the progression of the disease.

“​​Autosomal dominant polycystic kidney disease (ADPKD) is an incurable genetic disease affecting over 600,000 people in the United States and over 12 million people worldwide. If untreated, ADPKD leads to end-stage kidney failure in ~50% of patients by age 60, which underscores the significant need for therapies that slow down disease progression while preserving kidney function.” Further work is planned to explore this compound and others that can have an impact on treating PKD.