Developing Precision Medicine for Chronic Kidney Disease

August 18, 2021 - In a genome-wide association study, Perelman School of Medicine at the University of Pennsylvania researchers identified 182 genes potentially linked to kidney function and 88 genes for hypertension. Researchers can use these genes to target chronic kidney disease and improve precision medicine.

Chronic kidney disease impacted an estimated 850 million people and is responsible for 1 in 60 deaths worldwide. Currently, there are few treatments for chronic kidney disease. However, understanding the genetic variations linked to the disease is critical in developing new precision medicine treatments.

Through the study, researchers have created one of the clearest pictures to date of the genetic underpinning of chronic kidney disease, which will assist in the identification of potential treatment options.

“This is a key roadmap for understanding the mechanisms of chronic kidney disease,” principal investigator Katalin Susztak, MD, PhD, said in a press release. “Fortunately, some of the genes we’ve identified for kidney disease can be targeted with existing drugs.”

Chronic kidney disease is a growing global health issue and an economic burden. In 2018, the total Medicare spending for patients with kidney failure reached $36.6 billion and accounted for around 7 percent of all Medicare-paid claims costs, according to the Centers for Disease Control and Prevention (CDC).

While diabetes and high blood pressure play a role in chronic kidney disease development, the disease possess a strong heritable element, and genetic factors are increasingly identified as contributions to disease risk.

To understand the genetic variations of chronic kidney disease, researchers used genome-wide association studies to scan DNA variations across the complete genome in hundreds of thousands of people. While existing studies have identified about 300 regions in the human genome linked to chronic kidney disease, those maps did not pinpoint specific genes, cell types, and mechanisms.

“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,” said Susztak, who serves as a professor in the division of Renal-Electrolyte and Hypertension at Penn. “Our goal was to find the exact location of the treasure and to open up the box to see what was inside.”

The researchers generated gene expression and regulation data for each human kidney cell by using a recently developed single-cell sequencing method. The team then identify the key cell types where the genetic variant caused a faulty expression of genes.

The results identified almost 200 genes for kidney function and nearly 100 genes for hypertension. The team then clarified the mechanisms behind existing chronic kidney disease drugs, including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, to illustrate that they matched with the genes affected in the disease.

“We have used these drugs for several decades, but now we know why they work so effectively,” Susztak said. “This study represents a very important milestone for the nephrology field and the millions of patients currently affected by chronic kidney disease.”