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Cytokines and Immune Cell Phenotype in Acute Kidney Injury Associated With Immune Checkpoint Inhibitors
Naba Farooqui1, Mark Zaidi2, Lisa Vaughan3
1Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA.
Kidney International Reports
|March 20, 2023
Summary
Biomarkers like urine tumor necrosis factor alpha (TNF-α) can help distinguish acute kidney injury from immune checkpoint inhibitors (ICI-AKI) from other causes. This finding aids in diagnosing ICI-AKI and suggests potential therapeutic targets.
Area of Science:
- Nephrology
- Immunology
- Oncology
Background:
- Immune checkpoint inhibitors (ICIs) are crucial for cancer treatment but can cause acute kidney injury (AKI).
- Distinguishing ICI-associated AKI (AKI-ICI) from other causes of AKI (AKI-other) is challenging due to a lack of specific biomarkers.
- ICIs modulate immune pathways, suggesting immune cell dysregulation may be key in AKI-ICI pathogenesis.
Purpose of the Study:
- To identify biomarkers that can differentiate AKI-ICI from AKI-other.
- To investigate the role of T-cell activation and associated cytokines in AKI-ICI.
- To explore potential therapeutic targets within the TNF-α pathway.
Main Methods:
- Prospective study of 24 patients with AKI during ICI therapy (14 AKI-ICI, 10 AKI-other).
- Comparison of kidney injury markers, plasma/urine cytokines (including TNF-α, IFN-γ, ILs), and T-cell responses via mass cytometry.
- Analysis of immune cell populations in kidney tissue and systemic circulation.
Main Results:
- Patients with AKI-ICI showed increased kidney tissue immune cells (CD4 memory, T helper, dendritic cells) and urine cytokines (IL-2, IL-10, TNF-α) compared to AKI-other.
- Urine TNF-α demonstrated strong discriminatory ability for AKI-ICI (AUC=0.814).
- CD4+ T cells with a memory phenotype were the predominant subset.
Conclusions:
- Specific T-cell responses and cytokines, particularly urine TNF-α, can help differentiate AKI-ICI from AKI-other.
- Urine TNF-α is a promising biomarker for diagnosing AKI-ICI, often linked to acute interstitial nephritis (AIN).
- The TNF-α pathway presents a potential therapeutic target for AKI-ICI.
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