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Abstract: SA-PO149

Cytokines and Immune Cell Profiling in AKI Associated With Immune Checkpoint Inhibitors

Session Information

Category: Onconephrology

  • 1600 Onconephrology

Authors

  • Farooqui, Naba, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Ahsan, Eram, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Vaughan, Lisa E., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Taner, Timucin, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Leung, Nelson, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Alexander, Mariam P., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Herrmann, Sandra, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
Background

Immune checkpoint inhibitors(ICIs) can cause acute kidney injury(AKI-ICI), the most common histopathological finding being acute interstitial nephritis (AIN). Biomarkers can provide mechanistic insight into the pathophysiology of the AKI and may allow for early AKI-ICI detection which would help guide management. In this study, we investigated the associations between cytokines and immune cell profiling and AKI-ICI.

Methods

We prospectively included patients with AKI who were on ICI therapy and evaluated T-cell responses in peripheral mononuclear blood cells(PBMCs) and kidney tissue as well as urine and blood cytokines. Patient were adjudicated to either have a histological or clinical diagnosis of AIN [AKI-ICI(N=14)] or AKI due to other causes(e.g., acute tubular injury)[AKI-other (N=10)]. Kidney donors’ samples were also used as healthy controls(N=12). Imaging mass cytometry was used for immune cells profiling, and kidney tissue from a subset of patients with archived biopsy samples were also evaluated. Luminex assay was used to obtain urine and blood cytokines.

Results

Urine TNF-α levels were higher in the AKI-ICI group compared to AKI-other and healthy controls(Fig 1A), and tissue TNF-α expression was also significantly increased in AKI-ICI patients compered to controls.(Fig 1B).However, systemic TNF-α levels were not found to be significantly different between groups.(Fig 1C). Results from logistic regression predicting AKI type(AKI-ICI vs AKI-other) from TNF-α yielded strong discriminatory ability(AUC=0.814, 95% CI: 0.623-1.00). We also observed more pronounced increases of specific immune cells including CD4 memory, T helper and dendritic cells in the kidney tissue of patients who developed AKI-ICI compared to healthy controls.(Figs 1D, 1E, 1F).

Conclusion

These results suggest that increases in TNF-α and specific T-cell responses may contribute to AKI-ICI injury and could potentially serve as targets for therapeutic intervention as well as potential biomarkers.