ANTI-PD-1 Immunotherapy May Induce Interstitial Nephritis with Increased Tubular Epithelial Expression of PD-L1

Abstract Introduction Novel anti-cancer therapies include anti-program death-1 (PD-1) and anti-program death ligand -1 (PD-L1) drugs. These novel medications have side-effects in different organs, including the kidney. The most common adverse effect in the kidney is acute interstitial nephritis (AIN). No diagnostic criteria are available to distinguish between AIN associated with anti-PD-1 therapy from other AINs. Methods Kidney biopsies from patients on anti-PD-1 therapy were stained with antibodies to PD-1 and PD-L1. Herein we report morphologic and immunohistochemical findings in 15 patients who received anti-PD-1 therapy and developed acute kidney injury requiring a kidney biopsy. Results Among these patients, nine had AIN and six had no AIN, but showed acute tubular necrosis (ATN). Immunohistochemistry with antibodies to PD-1 and PD-L1 was performed on all these biopsies and on nine randomly selected biopsies with AIN from patients who did not receive anti-PD-1 medications, as well as nine patients with lupus nephritis and active appearing interstitial inflammation. There was weak staining for PD-1 in T cells in all patients with AIN and lupus, but tubular epithelial cell membrane staining for PD-L1 was seen only in patients with anti-PD-1 therapy-associated AIN, and not in patients with anti-PD-1 therapy-associated ATN, AIN secondary to other medications or in patients with lupus nephritis. Conclusions We propose that immunohistochemistry with PD-L1 could be used as a useful tool to differentiate between AIN associated with anti-PD-1 therapy from other AINs.