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A digital illustration of kidneys in the human anatomy

PHILADELPHIA – After mapping the genetic underpinning of kidney function in 1.5 million people and about 60,000 kidney cells that are the microscopic mechanisms of gene regulation, over 500 genes likely contribute to kidney disease development, according to researchers at the Perelman School of Medicine at the University of Pennsylvania. Multiple genes that play a key role in kidney detoxification, including SLC47A1, have been identified. The good news is that close to 100 of the 500 genes might be able to be targeted by various pharmaceuticals already approved by the Food and Drug Administration (FDA). The findings point to the underlying genetics of kidney function and can lead to future research into possible therapeutic targets to treat kidney disease and the development of it. The research was published in Nature Genetics.

“Single cell level analytical tools now allow us to dive deeper into the mechanisms at play by uncovering genetic variation in all cells in the body, and then we can look for links to genetics of diseases and illnesses,” said Katalin Susztak, MD, PhD, lead investigator and a professor of Nephrology and Genetics at Penn. “Highlighting the links and exploring cause and effect will offer greater understanding of the human kidney and uncover potential ways to treat those who struggle with kidney issues.”

An estimated 37 million people in the United States have kidney disease, and mortality from kidney disease has risen by more than 40 percent in the last two decades, making it one of the fastest-growing causes of death. Roughly a million people die of kidney failure worldwide each year. Despite the major personal and economic burden, few new therapeutics have been registered to treat or cure kidney disease over the last 40 years.

Using genetic information from more than 1.5 million participants around the world and a basic-science technique of mapping cells known as single-cell sequencing, scientists at Penn implicated important cell types for different disease conditions such as the proximal tubules for kidney disease and collecting duct principal cells for high blood pressure.

Next, the researchers characterized gene expression and gene regulation in hundreds of human kidney samples and analyzed changes in more than 60,000 human kidney cells. The team used sophisticated computational and statistical methods to generate the most comprehensive maps to uncover the genes, cell types and mechanism of kidney dysfunction.

“While there may be many origins of kidney dysfunction in human kidneys, our studies specifically highlight the role of SLC471A gene,” said Hongbo Liu, PhD, a postdoctoral fellow in Susztak’ s lab. “This gene carries different toxins. Changes in SLC47 might make the kidneys of people more or less sensitive to toxin mediated injury and kidney disease.”

The study authors want to continue to look into specific genes to understand their role in kidney diseases and say that their study serves as a springboard for researchers to test different pharmaceuticals against these genetic variants and their deleterious effects.

“There may come a time many years from now when patients who have these genetic variants can receive treatment before kidney disorders arise,” Susztak said.

This research was supported by the National Institutes of Health (R01DK087653, R01DK076077, and R01DK105821). Datasets produced in this study are available at


Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.

The Perelman School of Medicine is consistently among the nation's top recipients of funding from the National Institutes of Health, with $550 million awarded in the 2022 fiscal year. Home to a proud history of “firsts” in medicine, Penn Medicine teams have pioneered discoveries and innovations that have shaped modern medicine, including recent breakthroughs such as CAR T cell therapy for cancer and the mRNA technology used in COVID-19 vaccines.

The University of Pennsylvania Health System’s patient care facilities stretch from the Susquehanna River in Pennsylvania to the New Jersey shore. These include the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Chester County Hospital, Lancaster General Health, Penn Medicine Princeton Health, and Pennsylvania Hospital—the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

Penn Medicine is an $11.1 billion enterprise powered by more than 49,000 talented faculty and staff.

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