Genomics Reveals New Path for Chronic Kidney Disease Prevention

In a new study from Indiana University School of Medicine, a team of researchers and scientists have used genomics to discover alternative ways to treat kidney infections, increasing chronic kidney disease prevention.

Urinary tract infections are of the most frequent bacteria-causing infections that impacts people of all ages. If left untreated, UTIs can become server kidney infections, which could lead to chronic kidney disease. Kidney infections are considered common and occur in 13 out of 10,000 females and 4 of 10,000 males each year.

Kidney infections can cause high fevers, permanent kidney damage, and even sepsis. Recent data has suggested that cases of antibiotic resistant UTIs are surging, creating the potential for more UTIs to become serious kidney infections and chronic kidney disease.

The team of researchers discovered a type of cells called “intercalated cells” within the kidney. These cells take part in phagocytosis, which has historically only been associated with white blood cells.

"If you were to increase white blood cell activity to treat an infection, you would affect a person's whole body. However, since we found these cells work the same way but are only present in the kidney, the long-term potential would be the ability to activate these cells to prevent or clear an infection from the kidney," Andrew Schwaderer, MD, professor of pediatrics at IU School of Medicine, and one of the study's senior authors said in a press release.

"The idea is that with this approach we will eventually be able to replace or complement antibiotic therapy,” Schwaderer added.

The intercalated cells are found at the exit of the kidney and can act as guards. These cells are the first to meet the bacteria as it invades the kidney and then secretes acid to neutralize it.

Researchers originally predicted this pathway by using single-cell RNA sequencing they had available through the IU School of Medicine’s Medical Genomics Core. By using normal human kidney tissue, the researchers were able to sequence every intercalated cell individually.

The one-by-one sequencing allowed researchers to see what was going on in one cell versus another. Once the cells were analyzed, researchers hypothesized the phagocytosis capabilities of the cells were a leading function.

Following the human tissue test, researchers tested their theory by imaging mice in real time. This method is preferred to a cell culture system, which may or may not reflect results in the human body.

“It was also interesting that we started with human tissue as opposed to mouse models and then went back to the mouse,” Vijay Saxena, PhD and lead author of this study, said in a press release. "It's a very nonbiased way to study a cellular function and a very translational approach.”