Clinical Trial to Help Patients Undergoing Cancer Immunotherapy

Yale School of Medicine’s Dennis Moledina, MD, has focused his scientific career on finding a biomarker to identify kidney inflammation and injury caused by a reaction to medications, also known as acute interstitial nephritis. In a new study, he hopes to use this biomarker to address a rising clinical problem.

“Immune checkpoint inhibitors have revolutionized cancer care, and more than a million people are eligible to receive these remarkable drugs,” said Moledina, an associate professor in the Section of Nephrology. “However, there is a risk of an immune reaction to these medicines that can manifest in the kidneys as acute interstitial nephritis.”

One in five patients develops acute kidney injury within the first year of starting cancer immunotherapy, and determining if the checkpoint inhibitors are causing acute interstitial nephritis has important implications for cancer treatment, Moledina explained.

In a Q&A, Moledina discusses the effects of cancer immunotherapy on the kidneys and how he hopes his clinical trial will improve the care of cancer patients.

Cancer immunotherapy works by encouraging immune cells—T cells in the body—to attack cancer cells. But in some patients, these immune cells end up attacking the body’s own organs, including the liver, heart, skin, or kidneys. My research focuses on the effect of these immunotherapies on the kidneys.

Acute kidney injury is an umbrella term for a rise in creatinine in the blood, which indicates decreased kidney function. Many things can cause that increase in creatinine, one of which is checkpoint nephritis—an immune reaction to immune checkpoint inhibitors. However, most acute kidney injury is caused by dehydration, infection, or other factors. Figuring out whether this bump in creatinine is from checkpoint nephritis or other causes impacts the course of cancer treatment. Wrongly assumed checkpoint nephritis can lead to unnecessary steroid therapy and a pause in immunotherapy treatment, potentially allowing the cancer to progress. Missed checkpoint nephritis can lead to permanent kidney damage and the inability to qualify for chemotherapy.

This multi-center study, enrolling all patients who develop acute kidney injury at Yale, Johns Hopkins, Brigham and Women’s Hospital, and Mass General Hospital, will determine whether the biomarker CXCL9 can separate checkpoint nephritis from other causes of acute kidney injury.

We envision that, in the future, if a patient on cancer immunotherapy experiences acute kidney injury, we’ll be able to order a test to detect CXCL9 in the urine. If the value is high, we’ll know that it's from the immune checkpoint inhibitor and rapidly treat these patients with prednisone or other immunosuppressive therapy to minimize the pause in therapy. If the level is low, we can address the other cause of acute kidney injury without stopping treatment.

We hope our findings will help patients with acute kidney injury continue receiving cancer immunotherapy with as little interruption as possible.

For more information on the trial, or to enroll, visit Impact of Cancer Immunotherapy on the Kidneys.

Yale School of Medicine’s Department of Internal Medicine Section of Nephrology is committed to excellence in patient care, research, and education with the goal for both their faculty and trainees to be national and international leaders in the field of academic nephrology. To learn more about their mission and work, visit Nephrology.