Proton pump inhibitors and adverse kidney outcomes during immune checkpoint blockade: time to sound the alarm?

Abstract

Immune checkpoint inhibitors (ICI) have significantly altered the treatment landscape for cancer in the last decade. However, their benefits are often offset by therapy-limiting immune-related adverse events (irAEs). Acute interstitial nephritis (AIN) is the most common renal irAE, but the exact mechanisms underlying its development is poorly understood. ICI-induced immune activation against drug-derived antigens, leading to an inflammatory response within the kidney interstitium, have been postulated, evidenced by current observations of a higher incidence of ICI-AIN in patients receiving AIN-inducing drugs such as proton pump inhibitors (PPI). The role of PPIs in this specific context has garnered significant attention, given their ubiquitous use and sometimes, misuse. In this issue of CKJ Miao et al. summarise and synthesize best available evidence to clarify the interactions of PPI with ICI in the development of AIN and other adverse kidney outcomes. The sum of evidence provided appear to implicate PPI in the development of clinically significant short- and long-term kidney-related adverse effects in patients on immune checkpoint blockade, although causality cannot be proven. In this editorial, we discuss the key practical implications of these findings, and emphasize the need for further quality studies to delineate the true relationship of ICI and PPI in the development of AIN.