The nephrotoxicity of new immunotherapies

ABSTRACT

Introduction: Advanced cancers that did not respond to chemotherapy were once a death sentence, but now there are newer therapies utilizing the patient’s own immune system to fight cancer that are proving effective in chemotherapy-refractory malignancies. However, this success against cancer cells may be accompanied by immune-related adverse events that can affect the kidneys.

Areas covered: Using Medline and Scopus, we compiled all publications through February 2019 that pertained to immune checkpoint inhibitors (ICPIs) and chimeric antigen receptor T-cells (CAR T-cells).  The focus of this review is the discussion of these new cancer therapies, with attention to the reported kidney-related adverse effects..

Expert opinion: Autoimmunity is repressed by molecular pathways that inhibit T-cell activation against selected antigens. These self-protective mechanisms have been appropriated by tumor cells as a means of evading immune detection and destruction. New immunotherapies such as immune checkpoint inhibitors and chimeric antigen receptor T-cell therapy incite an aggressive immune response directed against tumor cells. This unrestrained activation of the immune system may result in kidney injury via multiple mechanisms.

KEYWORDS:

• Cancer immunotherapy
• immune checkpoint inhibitors
• chimeric antigen receptor T-cells
• acute kidney injury
• acute interstitial nephritis

Article highlights

1. At the forefront of cancer treatment are immunotherapies such as immune checkpoint inhibitors (ICPIs) and chimeric antigen receptor (CAR) T-cells, which activate the patient’s immune system against tumor cells.

2. Immunotherapies have proven successful against many different cancer types, but carry significant adverse effect profiles that include damage to the kidney via multiple mechanisms.

3. Data from early clinical trials of ICPIs suggested a relatively low incidence of immune-related adverse events affecting the kidney, but following widespread use, case reports and unpublished cohort study data suggest a higher incidence than previously recognized.

4. CAR T-cell use is not yet widespread, so kidney-related adverse effects remain incompletely characterized but notably include hemodynamic and cytokine-related damage as well as electrolyte derangements.

5. There exist major challenges in further development of immunotherapies to improve efficacy, safety, and cost profiles, and current research looks promising.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.