UPenn Researchers Identify Genes Responsible for Kidney Function and Related Hypertension

UPenn research is expected to enable hospitals and nephrology groups to offer precision medicine kidney treatment using existing medications

New research may lead to precision medicine that would enable hospital and health system CEOs to develop clinical service lines that improve outcomes for patients with chronic kidney disease (CKD). Because of the increased number of risk adjustment programs, such as with Medicare Advantage plans, improved diagnosis and treatment of CKD patients also could trigger substantial financial benefits.

Another interesting element of this research is that it maps a path for physicians and health systems to better utilize existing medications to maximum effect when treating patients with CKD. That alone could have a major clinical impact because the Centers for Disease Control and Prevention (CDC) reports that 15% of US adults (37 million) have CKD, also known as nephropathy.

What makes improved treatment of chronic kidney disease an ideal target for a precision medicine program are these two facts, provided by the CDC:

• As many as nine in 10 adults with CKD do not know they have CKD.
• About two in five adults with severe CKD do not know they have CKD.

Using Genetics to Develop Precision Medicine Treatments for Kidney Disease

Despite its widespread effects, the genetics influencing kidney disease are not well understood. Also, research in precision medicine kidney treatment is still quite new. For these reasons, researchers at the UPenn School of Medicine, led by Professor of Medicine Katalin Susztak, MD, PhD, recognized the unmet need for research addressing the genes influencing kidney function.

In a 2020 article published in Nature Reviews Nephrology, titled, “Unraveling the Complex Genetics of Common Kidney Diseases: from Variants to Mechanisms,” the UPenn researchers wrote, “Defining the target genes, cell types, and underlying mechanisms involved in kidney disease will be crucial for the development of new translational approaches and drugs in nephrology, which are desperately needed.” 

Toward that goal, in 2021, UPenn researchers identified, for the first time, almost two hundred genes responsible for kidney function. The good news is that many of these genes can be targeted using existing medications.

Susztak’s lab collected more than 650 different kidney samples and analyzed the gene expression and genetic difference of each sample. This extensive project not only enabled researchers to identify 182 genes responsible for kidney function, but additionally allowed them to identify 88 genes associated with hypertension related to the kidneys.

Susztak believes her team’s findings will help clinicians provide more targeted research and treatments. “The existing maps have indicated regions in the genome for kidney disease heritability, like an initial treasure map, but, until now, we did not know where the treasure chest was located or how it looked,” Susztak said in a recent news release.

“Our goal was to find the exact location of the treasure and to open up the box to see what was inside,” said, Katalin Susztak, MD, PhD (above), Professor of Medicine at the Perelman School of Medicine at the University of Pennsylvania. “The study provides one of the clearest pictures to date of the genetic underpinnings of chronic kidney disease. And it paves the way for the identification of potential treatments, which are critically needed.” (Photo copyright: University of Pennsylvania)

Improved Precision Medicine Treatments for Kidney Disease

Previous precision medicine research in nephrology focused on general areas of the genome or certain biomarkers but did not identify the specific genes that affect kidney function.

While these earlier and more general areas of research yielded important results—such as the ability to predict declining kidney function in patients with diabetes—understanding the actual genes controlling the kidneys is essential to advancing personalized medicine in nephrology.

Through their research, the UPenn researchers have laid the foundation for improved precision medicine treatments for kidney disease and provided insights into applications that could be immediately implemented by hospitals, integrated delivery networks (IDNs), and nephrology groups.

Susztak identifies two key benefits to their research:

• Improving the understanding of how existing treatments and prescription drugs work in patients with CKD, and
• Providing more precise targets for existing medications when treating CKD patients.

Medications that have been used for years now have a better context based on the genes they affect. “We have used these drugs for several decades, but now we know why they work so effectively,” Susztak explained. “This study represents a very important milestone for the nephrology field and the millions of patients currently affected by chronic kidney disease.”

Perhaps the most immediately impactful finding is the ability to better individualize treatment of kidney disease using existing medications. “This is a key roadmap for understanding the mechanisms of chronic kidney disease,” Susztak said. “Fortunately, some of the genes we’ve identified for kidney disease can be targeted with existing drugs.”

By using already-available medications to treat identified genetic biomarkers, hospitals can offer precision medicine kidney treatments, which will attract more patients without adding significant capital expenses. And increased patient acquisition, coupled with additional genetic testing offerings, provides hospitals with a new revenue opportunity.

Nephrologists and hospital administrators of healthcare systems that offer nephrology services will benefit from understanding the precision medicine implications of the UPenn team’s research. Becoming familiar with the different ways this research can be applied will allow rapid integration of these findings into clinical practice.

—Caleb Williams

Related Information:

Mapping the Genetic Architecture of Human Traits to Cell Types in the Kidney Identifies Mechanisms of Disease and Potential Treatments

Penn Researchers Unlock Genetic ‘Treasure Map’ for Chronic Kidney Disease

Unravelling the Complex Genetics of Common Kidney Diseases: from Variants to Mechanisms

Precision Medicine in Nephrology

Chronic Kidney Disease in the United States, 2021