Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Apr 29;5(8):1139-1148.
doi: 10.1016/j.ekir.2020.04.018. eCollection 2020 Aug.

Immune Checkpoint Inhibitors and Immune-Related Adverse Renal Events

Sandra M Herrmann  1 , Mark A Perazella  2   3
Affiliations
Review

Immune Checkpoint Inhibitors and Immune-Related Adverse Renal Events

Sandra M Herrmann et al. Kidney Int Rep. .

Abstract

Renal toxicities have been increasingly recognized as complications of the immune checkpoint inhibitors (ICIs). Recent studies have outlined the incidence and potential risk factors for nephrotoxicity. For clinicians, the key question is how to manage patients who develop these adverse renal effects. This is of paramount importance to providers as ICI use for cancer therapy becomes more widespread and nephrotoxicity increasingly develops. As clinicians encounter ICI-associated nephrotoxicity, an appropriate approach to management is required to facilitate the best outcomes in patients with cancer. Importantly, ICI rechallenge in patients who developed ICI-related acute kidney injury (AKI) is unclear and represents a conundrum for providers. Clinicians struggle with the "if, when, and how to" questions related to ICI rechallenge in this subset of patients. In addition, ICI use in the transplant population raises concerns for promoting acute rejection when treating cancer in these patients. We herein review current information on these various topics.

Keywords: CTLA-4; PD-L1; PD1; acute intertitial nephritis; immune checkpoint inhibitors; immunotherapy; renal immune-related adverse effect.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Immune-related adverse events. Various organs can be affected in immune-mediated injury caused by immune checkpoint inhibitors. C3GN, C3 glomerulopathy; FSGS, focal segmental glomerulosclerosis; GN, glomerulonephritis; MN, membranous nephropathy. Copyright © Mayo Clinic. Used with permission.
Figure 2
Figure 2
Immune checkpoint inhibitor (ICI)–related hyponatremia. Endocrinopathies involving the pituitary, thyroid, and adrenal glands may develop in patients treated with ICIs, which can lead to hyponatremia. ACTH, adrenocorticotropic hormone; TSH, thyroid-stimulating hormone.
Figure 3
Figure 3
Approach to immune checkpoint inhibitor (ICI) nephrotoxicity and rechallenge. AIN, acute interstitial nephritis; AKI, acute kidney injury; ATN, acute tubular necrosis; CRP, C-reactive protein; GN, glomerulonephritis; iRAE, immune-related adverse event; RBC, red blood cell; RTA, renal tubular acidosis; UA, urinalysis; WBC, white blood cell.
See this image and copyright information in PMC

References

    1. Hodi F.S., O'Day S.J., McDermott D.F. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–723. - PMC - PubMed
    1. Gandhi L., Rodriguez-Abreu D., Gadgeel S. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018;378:2078–2092. - PubMed
    1. Hamid O., Robert C., Daud A. Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Ann Oncol. 2019;30:582–588. - PMC - PubMed
    1. Leach D.R., Krummel M.F., Allison J.P. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996;271:1734–1736. - PubMed
    1. Boussiotis V.A. Molecular and biochemical aspects of the PD-1 checkpoint pathway. N Engl J Med. 2016;375:1767–1778. - PMC - PubMed

LinkOut - more resources