Immune checkpoint inhibitors and their interaction with proton pump inhibitors–related interstitial nephritis

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy and outcomes, leading to an expanding use in millions of patients worldwide. However, they can cause a spectrum of immune-related adverse events (irAEs). Essentially, any organs can be affected by irAEs, which have emerged as therapy-limiting side effects. In the kidneys, ICI-associated acute interstitial nephritis (ICI-AIN) leads to acute kidney injury (AKI) in 2%–5% of patients on ICI therapy. AKI associated with ICI therapy pathologically presents with AIN in nearly 90% of the cases, but the pathophysiology of ICI-AIN remains to be defined. The generation of autoreactive T cells in patients receiving AIN-inducible drugs, such as proton pump inhibitors (PPIs), is one of the leading theories, supported by a higher incidence of ICI-AIN in patients on these AIN-inducible drugs. In this review, we will discuss our understanding of the incidence, potential pathophysiological mechanisms, clinical presentations, risk factors, diagnosis, and management of PPI-related AIN and its interaction with ICI therapy.