Renal Toxicity Related to Immune Checkpoint Inhibitors

As early as the 18th century, physicians noticed that some cancer patients went into remission after developing fevers from infections. This led to the idea that the immune system, which protects from infection, might also fight cancer. What is now known as “immunotherapy” is a treatment that targets the immune system to recognize and eradicate cancer cells. Modern immunotherapy has focused on “checkpoint” proteins, such as cytotoxic T-lymphocyte-associated-protein-4 (CTLA-4) and programmed death-1 protein (PD-1), which are receptors on the surface of immune cells that act like a brake, or checkpoint, preventing the development of autoimmunity.1 The CTLA-4 receptor has homology to the T-cell activator co-stimulatory molecule CD28 and prevents T-cell activation by outcompeting CD28 for its ligand, the B7 receptor on antigen presenting cells (APCs).2 Likewise, binding of PD-1 with programmed death ligand 1 (PD-L1) — a protein expressed by immune, endothelial, and neoplastic cells — results in T-cell anergy.3 In both cases, an unwanted inflammatory response is suppressed. UPMC RENAL GRAND ROUNDS