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Review
. 2024 Feb 23:15:1353339.
doi: 10.3389/fimmu.2024.1353339. eCollection 2024.

Immune checkpoint inhibitors and acute kidney injury

Ping Zhou  1 , Ying Gao  2 , Zhijuan Kong  2 , Junlin Wang  2 , Shuxuan Si  2 , Wei Han  2 , Jie Li  2 , Zhimei Lv  1   2 , Rong Wang  1   2
Affiliations
Review

Immune checkpoint inhibitors and acute kidney injury

Ping Zhou et al. Front Immunol. .

Abstract

As a new type of anti-tumor immunotherapy, immune checkpoint inhibitors (ICIs) have improved the prognosis of multiple malignancies. However, renal complications are becoming more frequent. Nephrotoxicity often manifests as acute kidney injury (AKI), and the most common histopathological type is acute tubulointerstitial nephritis (ATIN). Based on previous studies of the incidence and potential risk factors for nephrotoxicity, in this review, we describe the mechanism of AKI after ICIs treatment, summarize the incidence, risk factors, and outcomes of AKI, and discuss the diagnosis and management of immune checkpoint inhibitors-associated acute kidney injury (ICI-AKI). In addition, we review the current status of ICIs rechallenge and the therapeutic strategies of ICIs applied in kidney transplant recipients. Finally, we emphasize the importance of collaboration between nephrologists and oncologists to guide the treatment of ICIs and the management of renal complications.

Keywords: acute kidney injury; immune checkpoint inhibitors; immune-related adverse events; immunotherapy; malignancies; nephrotoxicity.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Effect of ICIs (anti-CTLA-4 and anti-PD-1) on T-cell function. Anti-CTLA-4 checkpoint inhibitors enhance anti-tumor response by promoting the activation of quiescent T cells in lymph nodes. Anti-PD-1 checkpoint inhibitors impede the exhaustion of activated T cells by blocking of the PD-1 axis. ICIs, immune checkpoint inhibitors; PD-1, programmed cell death receptor-1; PD-L1, programmed cell death ligand-1; PD-L2, programmed cell death ligand-2; CTLA-4, cytotoxic T lymphocyte-associated antigen-4; TAA, tumor-associated antigens; MHC, major histocompatibility complex; TCR, T cell receptor.
Figure 2
Figure 2
Possible mechanisms of ICI-AKI. ICIs, immune checkpoint inhibitors; ICI-AKI, immune checkpoint inhibitors-associated acute kidney injury.
Figure 3
Figure 3
Diagnosis and treatment recommendations for ICI-AKI. ICIs, immune checkpoint inhibitors; SCr, serum creatinine; KDIGO, Kidney Disease Improving Global Outcomes; AKI, acute kidney injury; AIN, acute interstitial nephritis; FeNa, fractional excretion of sodium; FeUrea, fractional excretion of urea; ICI-AKI, immune checkpoint inhibitors-associated acute kidney injury; ATI, acute tubular injury; ATN, acute tubular nephritis; ATIN, acute tubulointerstitial nephritis.
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The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by National Natural Science Foundation of China (Grant: 81873615, 82070744, 81770723, 81400732), Academic promotion programme of Shandong First Medical University (NO: 2019QL022) and Taishan Scholars Program (NO: ts201712090, tsqn201812138)