What is the most common adverse kidney effect seen with immune checkpoint inhibitors?
Immune checkpoint inhibitors include the anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody as well as anti-programmed death antibodies (programmed cell death [PD]-1).
These antibodies serve to enhance the innate anti-tumor T-cell immunity leading to tumor regression and the stabilization of solid tumors. Immune checkpoint inhibitor kidney toxicity is an immune-mediated process.
Acute interstitial nephritis (AIN) is the most common biopsy finding reported with PD-1 inhibitors. Ipilimumab, a CTLA4 inhibitor, is also associated with AIN; however, podocytopathies, such as MN, MCD, and TMA, have also been reported.
Hyponatremia related to hypophysitis (inflammation of the pituitary gland) is also seen with CTLA4 antagonists.
The time of onset usually differs in the two drugs. CTLA4-antagonist-mediated injury usually occurs earlier within the first 2 to 3 months of use, while PD-1-inhibitor-mediated injury is usually seen later, 2 to 10 months into treatment.
Treatment usually involves the interruption of therapy and the use of high-dose steroids.