Renal Vasculitis and Pauci-immune Glomerulonephritis Associated With Immune Checkpoint Inhibitors

Abstract

Immune checkpoint inhibitors are increasingly used to treat a variety of solid-organ and hematologic cancers. However, overactivation of the immune system can lead to immune-related adverse events, which are increasingly recognized in the kidney. There have been only rare reported cases of checkpoint inhibitor-associated glomerulonephritis and renal vasculitis, although vasculitis in other organs has been well described. We report 4 cases of renal vasculitis or pauci-immune glomerulonephritis after checkpoint inhibitor therapy. Three patients had renal small- to medium-vessel vasculitis and 1 had focally crescentic pauci-immune glomerulonephritis. Three patients presented with acute kidney injury, and 1 presented with nephrotic syndrome and hematuria. Three patients were tested for antineutrophil cytoplasmic antibodies, which were negative. The time from checkpoint inhibitor initiation to immune-related adverse event presentation ranged from 2 weeks to 24 months. Three patients were treated with glucocorticoids, resulting in clinical resolution. Our series demonstrates that renal vasculitis and pauci-immune glomerulonephritis are important considerations in the differential diagnosis of checkpoint inhibitor-related reductions in kidney function.

Keywords: Checkpoint inhibitors; PD-1; PD-L1; acute interstitial nephritis (AIN); acute kidney injury (AKI); cancer; case report; drug toxicity; glomerulonephritis (GN); glucocorticoids; kidney biopsy; nivolumab; pembrolizumab; proteinuria; vasculitis.