Are CPIs associated with Acute Kidney Injury?
The immune system has the capacity to differentiate self from foreign invaders by the use of “checkpoints,” which allow cellular communication via cell surface receptors on T cells.
Cancer cells use tumor products acting via checkpoints to deactivate T cells. Ipilimumab, a CTLA-4 antibody, was the first CPI approved by the Food and Drug Administration (FDA).
Thereafter, immune-related adverse events were observed in many organ systems. Kidney toxicity from ipilimumab is rare but has been associated with granulomatous AIN. This was attributed to a steroid responsive autoimmune mechanism.
The CPIs, nivolumab and pembrolizumab, which are antiprogrammed cell death protein 1 (PD1) antibodies, have also been associated with AIN. Nephritogenic drugs (NSAIDs, PPIs) may prime drug-specific effector T-cells and then the drug-induced inhibition of the PD-1 pathway, resulting in a loss of tolerance and AIN.
An alternate hypothesis is that PD-1 inhibition causes a loss of T-cell self-tolerance, resulting in a general autoimmune disease in the kidney.