Cancer immunotherapy, while revolutionary, carries the risk of immune-related adverse events, including acute kidney injury (AKI). A new clinical trial led by Yale School of Medicine's Dr. Dennis Moledina aims to identify a biomarker that can distinguish between checkpoint nephritis and other causes of AKI in patients undergoing cancer immunotherapy. This distinction is crucial because misdiagnosis can lead to unnecessary steroid therapy and pauses in immunotherapy, potentially allowing cancer progression, while missed checkpoint nephritis can result in permanent kidney damage.
The Challenge of Acute Kidney Injury in Immunotherapy
Immune checkpoint inhibitors, a cornerstone of modern cancer treatment, can trigger immune cells to attack not only cancer cells but also healthy organs, including the kidneys. According to Dr. Moledina, approximately one in five patients receiving cancer immunotherapy develops AKI within the first year. The difficulty lies in determining whether the AKI is a direct result of the immunotherapy (checkpoint nephritis) or due to other common causes such as dehydration or infection.
CXCL9 as a Potential Biomarker
The multi-center study, involving Yale, Johns Hopkins, Brigham and Women’s Hospital, and Mass General Hospital, is evaluating whether the biomarker CXCL9 can effectively differentiate checkpoint nephritis from other causes of AKI. The researchers hypothesize that elevated levels of CXCL9 in urine samples may indicate checkpoint nephritis.
Implications for Patient Care
"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," Dr. Moledina explained. "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."
The ultimate goal is to enable patients with AKI to continue receiving potentially life-saving cancer immunotherapy with minimal interruption, improving both cancer outcomes and kidney health.
