title: Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Kidney Diseases and Hypertension, Hofstra Northwell School of Medicine, Great Neck, USA.
authors.forename: Rimda
authors.initials: R
authors.lastname: Wanchoo
authors.forename: Sabine
authors.initials: S
authors.lastname: Karam
authors.forename: Nupur N
authors.initials: NN
authors.lastname: Uppal
authors.forename: Valerie S
authors.initials: VS
authors.lastname: Barta
authors.forename: Gilbert
authors.initials: G
authors.lastname: Deray
authors.forename: Craig
authors.initials: C
authors.lastname: Devoe
authors.forename: Vincent
authors.initials: V
authors.lastname: Launay-Vacher
authors.forename: Kenar D
authors.initials: KD
authors.lastname: Jhaveri
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000453:epidemiology / Q000276:immunology / Q000473:pathology; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D061025:Costimulatory and Inhibitory T-Cell Receptors / Q000037:antagonists & inhibitors*; D004359:Drug Therapy, Combination / Q000009:adverse effects; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects* / Q000379:methods; D015994:Incidence; D007668:Kidney / Q000276:immunology / Q000473:pathology; D009369:Neoplasms / Q000628:therapy*; D009395:Nephritis, Interstitial / Q000139:chemically induced / Q000453:epidemiology / Q000276:immunology
chemical_list: D000074322:Antineoplastic Agents, Immunological; D061025:Costimulatory and Inhibitory T-Cell Receptors