UT lab tries to derail chronic kidney disease on a molecular level
Our kidneys remove waste from our blood and maintain fluid balance in our body.
Chronic kidney disease (CKD) is a condition where the kidneys are damaged over a period of time to the point that they cannot filter waste products from blood properly.
CKD is one of the most common diseases in the United States affecting 10 to 5 percent of the population (37 million people). While there are many factors that contribute to the development and progression of CKD, conditions such as diabetes, high blood pressure, obesity, smoking, family history, and aging are the most frequent contributors. Often, people with CKD do not show symptoms during the early stages, when treatment would be more effective, instead the disease progresses to more advanced stages that are difficult to treat.
Doctors have divided CKD into different stages based on the kidneys’ efficiency and speed of filtration (called glomerular filtration rate). At the early stage of CKD, kidneys can perform most of their normal functions. At the most advanced stage, called end-stage kidney disease, glomerular filtration rate drops to less than 15 percent of normal function, indicating permanent kidney damage. At this stage, dangerous levels of fluids, electrolytes, and waste can build up in the body.
The only available treatments for end-stage kidney disease are kidney transplant or dialysis, but these treatments come with high cost and side effects. Therefore, it is important to detect and treat CKD at early stages.
At the University of Toledo College of Medicine and Life Sciences, many research labs, including mine, study the underlying molecular mechanisms of CKD, to find a permanent cure for this devastating disease, or to find a way to slow down its progression by detecting CKD at an early stage.
I am investigating a molecule that our body makes called 20-HETE. This is a lipid molecule thought to be one of the major molecules produced by the kidneys. Under normal conditions, this molecule helps to regulate water and salt balance in our body. However, an increased level of 20-HETE is found in CKD patients. Thus, we are investigating if these high levels of 20-HETE damages kidneys and to discover ways to prevent this damage.
How are we doing this? We are searching for possible receptors for 20-HETE.
Receptors are proteins found on cell surfaces that bind to specific molecules. Some of these receptors act as gatekeepers of our cells. Only specific molecules can bind to these receptors and activate them, providing specific information to molecules inside the cells. This stimulates the cells to act in a certain way that can have good (physiological) or bad (pathological) outcomes.
Our lab is now focused on a cellular pump in kidney cells, called the Sodium-Potassium ATPase, which also acts as a receptor for specific molecules. Continuous activation of this receptor can damage the kidneys. Therefore, we think that Sodium-Potassium ATPase may act as receptor for 20-HETE. I use advanced molecular techniques to study kidney cells in culture media. My research also involves using powerful supercomputers to simulate the effects of molecules like 20-HETE in the kidney
My preliminary investigation shows that 20-HETE binds the Sodium-Potassium ATPase. Therefore when increased levels of 20-HETE continuously stimulates this receptor, it sends pathological signals which damage the kidney cells and form scar tissue. If this continues for a long time, there is a risk of significant kidney damage.
The good news is that once we figure out the underlying mechanism(s), we can then target these molecular interactions with new therapies to treat CKD and prevent its progression.
There is a tremendous amount that remains unknown about the function of 20-HETE in the kidneys. Our lab uses state-of-the-art techniques to investigate new ways to answer questions about how this molecule works and how we can target it to prevent or treat kidney damage. Our goal is to help contribute to new preventative, diagnostic, and treatment strategies aimed at combatting the significant health issues that CKD patients face.
Dhilhani is a Ph.D. student in the Department of Medicine in The University of Toledo College of Medicine and Life Sciences Biomedical Science Program. Dhilhani is conducting her research in the laboratory of Dr. David J. Kennedy. For more information, contact FathimaDhilhani.MohammedFaleel@rockets.utoledo.edu or go to www.utoledo.edu .