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Nephrotoxicity of Cancer Immunotherapies: Past, Present and Future
Mark A Perazella1,2, Anushree C Shirali3
1Section of Nephrology, Department of Medicine, Yale University, New Haven, Connecticut; and mark.perazella@yale.edu.
Abstract:
Nephrotoxicity from cancer therapies is common and increasingly encountered in clinical practice, such that the subfield of "onco-nephrology" has emerged. Conventional chemotherapeutic drugs and novel agents targeting specific genes/proteins are effective cancer therapies but suffer from a number of adverse kidney effects. An effective avenue of cancer treatment is immunotherapy, which uses drugs that augment immune system-mediated recognition and targeting of tumor cells. As such, leveraging the immune system to target malignant cells represents an important modality in eradicating cancer. IFN and high-dose IL-2 are older immunotherapies used in clinical practice to treat various malignancies, whereas new cancer immunotherapies have emerged over the past decade that offer even more effective treatment options. The immune checkpoint inhibitors are an exciting addition to the cancer immunotherapy armamentarium. Chimeric antigen receptor T cells are also a new immunotherapy used to treat various hematologic malignancies. However, as with the conventional and targeted cancer agents, the immunotherapies are also associated with immune-related adverse effects, which includes nephrotoxicity.
Insights
Cancer therapies, including immunotherapy, can cause kidney damage (nephrotoxicity). Onco-nephrology addresses these adverse effects, highlighting the need for careful monitoring of kidney function during cancer treatment.
Area of Science:
- Oncology
- Nephrology
- Immunology
Background:
- Nephrotoxicity is a frequent complication of cancer treatments, necessitating the emergence of onco-nephrology.
- Both conventional chemotherapy and targeted agents can induce adverse kidney effects.
- Immunotherapy offers a promising cancer treatment modality by harnessing the immune system.
Purpose of the Study:
- To review the spectrum of nephrotoxicity associated with various cancer therapies, including conventional, targeted, and immunotherapies.
- To highlight the emergence and importance of the onco-nephrology subfield in managing these kidney-related adverse events.
- To discuss the mechanisms and clinical implications of immune-related adverse events affecting the kidneys.
Main Methods:
- Literature review of studies on cancer therapies and associated nephrotoxicity.
- Analysis of adverse event profiles for conventional chemotherapy, targeted agents, and immunotherapies.
- Synthesis of current understanding regarding immune-related adverse events (irAEs) impacting renal function.
Main Results:
- Conventional and targeted cancer drugs are known causes of nephrotoxicity.
- Emerging immunotherapies, such as immune checkpoint inhibitors and CAR T-cells, also present risks of kidney damage.
- Interferon (IFN) and high-dose Interleukin-2 (IL-2) are established immunotherapies with potential renal side effects.
Conclusions:
- Cancer therapies, particularly novel immunotherapies, are increasingly associated with significant nephrotoxicity.
- The field of onco-nephrology is crucial for managing kidney complications in cancer patients.
- Further research is needed to understand and mitigate the renal risks of modern cancer treatments.
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