Diagnosis and treatment of immune checkpoint inhibitor induced kidney disease.

The use of immune checkpoint inhibitors (ICIs) is expanding in the treatment of a variety of cancer types; however, treatment with ICIs may result in off-target kidney inflammation in 3-5% of patients, most commonly acute interstitial nephritis (AIN). There is a significant unmet need for noninvasive diagnostic tools to facilitate accurate and timely diagnosis, and for targeted therapeutic strategies to more specifically block inflammation in ICI-AIN. The most promising emerging noninvasive diagnostic strategies include novel urinary biomarkers such as C-X-C motif ligand 9 (CXCL9), tumor necrosis factor alpha (TNF-α), interleukin 5 (IL-5), and Fas. There are increasing data to support treatment strategies that may better preserve the antitumor effect of ICIs, including the use of infliximab, as well as shorter corticosteroid courses. Novel biomarkers have shown great potential, although further studies will be required for validation. Improving scientific understanding of the underlying immunobiology in ICI-AIN and other ICI toxicities may uncover new pathways amenable to more specific therapeutic targeting, such as TNF-α. General nephrologists should be aware of recent advances in biomarker discovery and second-line immunosuppressives, given the increasingly widespread use of ICIs.