Abstract: FR-PO025

Tubulitis in a Patient Treated with Nivolumab: Case Report and Literature Review

Session Information

Category: Nephrology Education

  • 1302 Fellows and Residents Case Reports

Authors

  • Vakil, Viral, University of Minnesota, Minneapolis, Minnesota, United States
  • Birkenbach, Mark, University of Minnesota, Minneapolis, Minnesota, United States
  • Woerner, Katti, University of Minnesota, Minneapolis, Minnesota, United States
  • Muhammad, Safwan, University of Minnesota, Minneapolis, Minnesota, United States
  • Bu, Lihong, University of Minnesota, Minneapolis, Minnesota, United States
Background

Immune checkpoint inhibitors are monoclonal antibodies that are increasingly approved by FDA for treatment of solid organ and hematologic malignancies by enhancing anti-tumor T cell immune response. Nivolumab is a monoclonal antibody targeting programmed death-1 (PD1), an inhibitory molecule expressed on cell surface of activated effector T cells. PD1 has two ligands programmed death ligand-1 (PD-L1) and programmed death ligand-2 (PD-L2), located on antigen presenting cells and hematopoietic cells respectively. Nivolumab prevents interaction of PD1 and PD-L1, allowing T cells to continue to attack tumor cells expressing PD-L1. Immune related adverse events (IRAEs), the effect of activated cytotoxic T cells on non-neoplastic antigens, are commonly seen across various organ systems. Renal toxicities associated with PD1 inhibitors are thought to be very low (0.9%), however some reports are more frequent and as high as 29%. Kidney injury associated with PD1 inhibitors commonly manifests as acute tubulointerstitial nephritis on kidney biopsy, with a late onset ranging from 3 to 10 months. Steroids appear to be effective in treating such IRAEs. Here we describe a patient with metastatic urothelial carcinoma treated with Nivolumab who develops acute kidney injury at 6 months after initiation of treatment. A renal biopsy showed focal moderate to severe tubulitis without evident interstitial inflammation. PD-L1 immunopositivity was detected only in tubules with lymphocytic tubulitis. The patient's renal function improved to baseline after withholding Nivolumab followed by prednisone treatment.

Kidney Biopsy under light microscopy (A) and immunohistochemical staining for PDL1 (B)