Immune checkpoint inhibitors associated granulomatous small vessel vasculitis accompanied with tubulointerstitial nephritis: a case report

Immune checkpoint inhibitors (ICIs) have provided significant benefits in cancer treatment, but they could develop immune-related adverse events (irAE). ICI-associated renal adverse effects are rare and tubulointerstitial nephritis (TIN) is the most common in the renal irAE. However, only a few case reports of renal vasculitis associated with ICI have been reported. In addition, the characteristics of infiltrating inflammatory cells of ICI-associated TIN and renal vasculitis have been uncertain. A 65-year-old man received immune checkpoint inhibitors (ICIs), anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) and anti-PD-1 (programmed cell death 1) antibodies for aggravated metastatic malignant melanoma. About 1 week after the second administration of nivolumab and ipilimumab, acute kidney injury developed. A renal biopsy was performed that showed TIN and non-necrotizing granulomatous vasculitis in interlobular arteries. Massive CD3 T cells and CD163 macrophages infiltrated both tubulointerstitium and interlobular arteries. Many infiltrating cells tested positive for Ki-67 and PD-1 ligand (PD-L1), but negative for PD-1. In CD3 T cells, CD8 T cells were predominantly infiltrated, and these cells were positive for Granzyme B (GrB) and cytotoxic granule TIA-1, but negative for CD25, indicating antigen-independent activated CD8 T cells. Infiltration of CD4 T cells was noted without obvious CD4 CD25 regulatory T (Treg) cells. His renal dysfunction recovered within 2 months of treatment with prednisolone in addition to discontinuation of nivolumab and ipilimumab. We herein reported a case of ICI-related TIN and renal granulomatous vasculitis with infiltration of massive antigen-independent activated CD8 T cells and CD163 macrophages, and none or few CD4 CD25 Treg cells. These infiltrating cells might be a characteristic of the development of renal irAE.