Immunological mechanisms underlying clinical phenotypes and noninvasive diagnosis of immune checkpoint inhibitor-induced kidney disease

Abstract

Immune checkpoint inhibitors (ICIs) have become a mainstay of cancer therapy, with over 80 FDA-approved indications. Used in a variety of settings and in combination with each other and with traditional chemotherapies, the hyperactive immune response induced by ICIs can often lead to immune-related adverse events in bystander normal tissues such as the kidneys, lungs, and the heart. In the kidneys, this immune-related adverse event manifests as acute interstitial nephritis (ICI-AIN). In the era of widespread ICI use, it becomes vital to understand the clinical manifestations of ICI-AIN and the importance of prompt diagnosis and management of these complications. In this review, we delve into the clinical phenotypes of ICI-AIN and how they differ from traditional drug-induced AIN. We also detail what is known about the mechanistic underpinnings of ICI-AIN and the important diagnostic and therapeutic implications behind harnessing those mechanisms to further our understanding of these events and to formulate effective treatment plans to manage ICI-AIN.

Keywords: Th1/Th2/Th17 cells; acute interstitial nephritis; biomarkers; immune-mediated diseases; immunotherapies.

FIGURE 1

Trend in FDA indications and clinical use of immune checkpoint inhibitors at Mass General Brigham.

FIGURE 2

Statistics on immune checkpoint inhibitors and kidney disease.