According to a news article published by the Yale School of Medicine, Yale University researchers recently determined that autosomal dominant polycystic kidney disease (ADPKD) could potentially be reversed. Head researcher Dr. Stefan Somlo, MD, sought to deepen his understanding of kidney function. In particular, he wanted to understand exactly how certain molecular pathways work in ADPKD and whether these can be reversed. In mice models, the researchers determined that it could be possible to reverse damage and prevent disease progression. Interested in learning more? Take a look at the full findings published in Nature Genetics.

The Research

Dr. Somlo has been studying kidney disease for the last 30+ years, working to understand it on a molecular biology level. Eventually, Dr. Somlo even created his own lab to better understand the underlying molecular and genetic elements associated with ADPKD. Within this particular study, the research team utilized mice models of polycystic kidney disease. They created these mice by inactivating the PKD2 gene, often associated with ADPKD. Next, researchers reactivated a healthy copy of the gene in mice (similar to what might happen in humans during gene therapy). Through this, researchers found:

• After PKD2 reactivation, kidney inflammation and fibrosis (scarring) were both found to be reversible.
• The treatment also helped to reduce the size of the kidneys, promote natural function and form, and reduce or fix any cysts.
• Overall, similar results were also observed in a secondary study focusing on PKD1, another gene associated with polycystic kidney disease.
• Researchers believe that polycystin expression helped reverse some of the damage associated with polycystic kidney disease. Additionally, researchers feel that polycystin expression could address changes in cell shape and growth. When the gene is expressed healthily, the polycystins help the kidneys to return to normal.
• Autophagy, or the bodily process of clearing out damaged cells to regenerate healthy cells, also occurred after “turning on” PKD1 or PKD2.
• Treatment must be administered in earlier disease stages. By the time ADPKD reaches late-stage, it is no longer possible to repair all of the damage.

While these findings are promising, there is still much to learn about certain pathways, how polycystins function, and how to create potential therapeutic options for patients. However, Dr. Somlo and his lab are committed to making this change.

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Autosomal dominant polycystic kidney disease (ADPKD) is the most common subset of polycystic kidney disease (PKD), a genetic disorder which prompts cyst growth in or on the kidneys. As these cysts develop, they cause scarring, inflammation, and damage. As a result, kidney function is impaired. As the name suggests, ADPKD is inherited in an autosomal dominant fashion. This means that patients must inherit only one defective gene from a parent to have ADPKD. Typically, symptoms appear between ages 30-50. These include:

• High blood pressure
• Kidney cysts over half an inch large
• Abdominal distention
• Headache
• Back, side, and rib/hip pain
• Hematuria (blood in the urine)
• Frequent urinary tract infections (UTIs)
• Liver or pancreatic cysts
• Kidney stones
• Fluttering or pounding in the chest
• Kidney failure
• Brain aneurysm