Ivana Kuo, PhD is an Assistant Professor with Stritch School of Medicine's Cell and Molecular Physiology Department   -Photo by Lukas Keapproth

Health Sciences Research

Kuo lab kidney research looks to aid in heart failure treatments

Our kidneys, the pair of organs charged with filtering our blood and controlling our body’s fluid levels, are normally the size of small oranges. But for someone with autosomal dominant polycystic kidney disease (ADPKD), their kidneys can grow to be the size of a football and weigh 30 pounds each.

ADPKD is a rare genetic disorder that causes cysts to grow in the kidneys, and eventually causes kidney failure. But as Loyola University Chicago researcher Ivana Kuo, PhD, has found, how ADPKD is also contributing to heart disease could be key in treating a common cardiac condition: congestive heart failure. 

“This has been intriguing for me as a basic science researcher, because it shifted my focus from a very specific genetic disorder to something that might have larger ramifications for millions of people with heart disease as well."

Kuo’s work is in partnership with Arlene Chapman, MD, a University of Chicago clinical nephrologist who studies high blood pressure, kidney disease, and cardiac complications in ADPKD.

 

‘This has been intriguing for me as a basic science researcher, because it shifted my focus from a very specific genetic disorder to something that might have larger ramifications for millions of people with heart disease as well.
— Ivana Kuo, PhD

 

One of the first symptoms of ADPKD is high blood pressure. Even those people with normal kidney function still have high blood pressure, as. But changes to the heart are happening even before hypertension even develops. 

The research of Kuo’s lab shows that the protein products of the ADPKD polycystin genes 1 and 2, , are also found in the heart. Intriguingly, the specific polycystin 2 (PC2) signaling pathway is increased during cardiac stress (the same cardiac stress that can lead to heart failure), resulting in the production of natriuretic peptides, which are the body’s own defense to cardiac stress. Natriuretic peptides are a good thing as the cause the kidneys to emit sodium, which lower blood pressure and have other helpful effects on both the heart and kidneys.

“The heart expressed the same protein that is mutated in the kidney and causes the cysts to develop in PKD,” explained Kuo. “Yet, this protein in the heart, if it’s not mutated, is very important as it controls the production of the very beneficial natriuretic peptides-and so we can potentially help those with heart failure”

10%

End-stage kidney disease

is a result of ADPKD.

90%

Polycystic Kidney Disease (PKD)

are inherited in an autosomal dominant fashion, meaning if you get the abnormal gene from only one parent, you can still get the disease.

20-30%

of kids with ADPKD

have high blood pressure.

Dr. Kuo is now applying for a CTSA-funded project with Dr. Chapman to see how manipulating and increasing PC2 pathways to maximize the production of the natriuretic peptides during incidents that stress the heart. They are also hoping to look at the heart tissue and blood samples of patients with congestive heart failure. They will look at the polycystin and natriuretic peptide levels and compare these vales to how well the patients are doing

The results of these studies could potentially help not only the people who are living with ADPKD or renal failure but also those with congestive heart failure. More than 12 million people worldwide have renal failure, and more than 26 million people are living with congestive heart failure symptoms. 

There is currently no cure for ADPKD, and any insight into the mechanics behind the disease would be helpful to scientists studying the genetic disease. Dr. Kuo and her fellow researchers are hoping the results help them do further research into both polycystic kidney disease and heart failure.

“You never know what kind of unexpected results you can get when doing research in the lab,” said Kuo. “This started out as kidney disease research, and we came upon these interesting results that could also impact heart disease. We’re hopeful that we will continue to receive funding to continue this research and hopefully affect a large number of patients.”

Video Courtesy of Chicago Institute for Translational Medicine.