Immune Checkpoint Inhibitor–Associated Acute Kidney Injury

Excerpt

Immune checkpoint inhibitors (ICIs), which target the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4), programmed death-1 (PD-1), programmed death–ligand-1 (PD-L1), and lymphocyte activation gene-3 (LAG-3) pathways, have revolutionized cancer treatment. In 2011, the Food and Drug Administration (FDA) approved ipilimumab (the first ICI) for the treatment of advanced melanoma. Since then, the number of approved ICIs and their indications have increased exponentially, demonstrating the extraordinary potential of these drugs in treating various tumors. Currently, 11 ICIs are approved for nearly 20 types of cancer, including melanoma, lung cancer, renal cell carcinoma, and endometrial cancer, with indications continuing to expand over time.

Although ICIs have improved the prognosis of many cancers, they are associated with a broad spectrum of adverse events known as immune-related adverse events (irAEs), which arise from increased autoimmunity. One of the notable irAEs is ICI-associated acute kidney injury (ICI-AKI), which most often presents as acute interstitial nephritis (ICI-AIN) on histopathology. ICI-AKI can have significant consequences, including kidney failure, interruption or discontinuation of lifesaving immunotherapy, prolonged immunosuppression, and increased mortality. Unlike adverse effects associated with conventional chemotherapy and radiation treatments, irAEs often have a prolonged course and delayed onset, necessitating long-term monitoring for these effects.