Immunotherapy have revolutionized treatment options for certain cancers. Drugs that are used for immunotherapy are commonly called as “immune checkpoint inhibitors.”
National Cancer Institute Dictionary of Cancer Terms defines an immune checkpoint inhibitor as “A type of drug that blocks certain proteins made by some types of immune system cells, such as T cells, and some cancer cells. These proteins help keep immune responses in check and can keep T cells from killing cancer cells. When these proteins are blocked, the “brakes” on the immune system are released and T cells are able to kill cancer cells better.” The examples of checkpoint proteins that are found on T cells or cancer cells include PD-1/PD-L1 and CTLA-4/B7-1/B7-2. The figures below show where these proteins are located.
Immune checkpoint (ICP) inhibitor drugs that are currently available for cancer treatments block either CTLA-4, PD-1 or PD-1L proteins.
The US Food and Drug Administration has approved ICP inhibitors for advanced or metastatic melanoma, non-small cell lung cancer, recurrent head and neck cancer, kidney cancer, urothelial cancer and Hodgkin lymphoma. They are also under investigation for many other types of cancers in clinical trials.
The adverse events associated with ICP inhibitors are mainly due to uninhibited immune system causing damage to body’s own cells. Areas of the body that get affected by these immune adverse reactions include skin, liver, colon, lung, thyroid gland, pituitary gland, adrenal glands and the kidney.
As ICP inhibitors are being used in treatment of more cancer types, more case series of kidney toxicity are being published in literature. The most common type of damage to kidneys with these drugs are acute injury to tubules and tubular space of the kidneys which is medically termed as” acute tubulointersitial nephritis”. Immune T-cells that lose the auto-control due to ICP inhibitors may also cause damage to filtering part of the kidneys which is defined as “glomerulonephritis”. These conditions are diagnosed by nephrologists with laboratory tests and kidney biopsy. Nephrologists help oncologists at both diagnosis and management of kidney related adverse events of immune checkpoint inhibitors. Treatments with corticosteroids have been shown to be beneficial at managing kidney toxicity of ICP inhibitors.