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Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative ReviewWanchoo R.a · Karam S.c · Uppal N.N.a · Barta V.S.a · Deray G.d · Devoe C.b · Launay-Vacher V.d, e · Jhaveri K.D.a · on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors
aDivision of Kidney Diseases and Hypertension, Hofstra Northwell School of Medicine, Great Neck, and bDivision of Hematology and Oncology, Hofstra Northwell School of Medicine and Northwell Cancer Institute, New Hyde Park, USA; cDepartment of Medicine, University of Balamand, Faculty of Medicine, Beirut, Lebanon; dNephrology Department, Pitié-Salpêtrière University Hospital, and eService ICAR, Pitié-Salpêtrière University Hospital, Paris, France
Kenar D. Jhaveri, MD
Professor of Medicine, Nephrology, Northwell Health
Hofstra Northwell School of Medicine
Great Neck, NY 11021 (USA)
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Background: Cancer immunotherapy, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death 1 (PD-1), has revolutionized the treatment of malignancies by engaging the patient's own immune system against the tumor rather than targeting the cancer directly. These therapies have demonstrated a significant benefit in the treatment of melanomas and other cancers. Summary: In order to provide an extensive overview of the renal toxicities induced by these agents, a Medline search was conducted of published literature related to ipilimumab-, pembrolizumab-, and nivolumab-induced kidney toxicity. In addition, primary data from the initial clinical trials of these agents and the FDA adverse reporting system database were also reviewed to determine renal adverse events. Acute interstitial nephritis (AIN), podocytopathy, and hyponatremia were toxicities caused by ipilimumab. The main adverse effect associated with both the PD-1 inhibitors was AIN. The onset of kidney injury seen with PD-1 inhibitors is usually late (3-10 months) compared to CTLA-4 antagonists related renal injury, which happens earlier (2-3 months). PD-1 as opposed to CTLA-4 inhibitors has been associated with kidney rejection in transplantation. Steroids appear to be effective in treating the immune-related adverse effects noted with these agents. Key Message: Although initially thought to be rare, the incidence rates of renal toxicities might be higher (9.9-29%) as identified by recent studies. As a result, obtaining knowledge about renal toxicities of immune checkpoint inhibitors is extremely important.
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