Immune checkpoint inhibitors (ICIs) have transformed treatment for many types of cancer. In some patients, however, ICIs are associated with immune-related complications that can affect the kidneys. These complications sometimes require care teams to pause or discontinue lifesaving treatment. A study led by Sandra Herrmann, M.D., an onconephrologist and researcher at Mayo Clinic, helps clarify how immune-related kidney inflammation develops and provides preclinical evidence supporting a targeted approach that could improve how these side effects are managed - and could potentially be prevented.
In the study, published in JCI Insight, Dr. Herrmann and a team of Mayo Clinic researchers explored how ICIs can trigger inflammation in the kidneys, which can lead to acute kidney injury. About 1 in 5 patients receiving ICIs develop acute kidney injury during treatment. While about 5% of these cases are most directly associated with ICI-induced interstitial nephritis, determining the cause can take time. Care teams must pause treatment for testing and, in some cases, discontinue ICI therapy - even if it's treating their cancer effectively.
"We don't want to stop this very important drug that helps your immune system fight cancer, so we need to be sure the immunotherapy is causing kidney injury and not something else," says Dr. Herrmann, senior author of the study.
To better understand and address these complications, Dr. Herrmann and her team developed a preclinical model to study how this inflammation occurs and how it could be treated or prevented.
"For the first time, we were able to reproduce in a lab model the same kidney inflammation we see in patients receiving immunotherapy. That gave us a platform to test targeted treatment for kidney inflammation that blocks the inflammatory signal TNF-alpha - an approach already used clinically for other immune-related conditions," says Dr. Herrmann.
The findings show that TNF-alpha blockade improved markers of kidney injury in preclinical models and could potentially be explored as a preventive approach in people receiving immunotherapy for cancer.
More research is needed to confirm the safety and effectiveness of this targeted approach. If successful, it could offer a more precise way to manage kidney-related side effects and improve current treatment strategies - which rely on steroids that broadly suppress the immune system and can interfere with its ability to fight cancer.
"Our goal is to develop targeted therapies for the ICI-induced kidney injury that enable continuation of immunotherapy, which many times can be lifesaving for patients," says Dr. Herrmann. "By targeting specific pathways, we can treat inflammation without interfering with the benefit of immunotherapy."
