title: Acute kidney injury following crizotinib administration for non-small-cell lung carcinoma.
abstract: A case of locally advanced non-small-cell lung carcinoma (NSCLC) was inadequately controlled with cisplatin, bevacizumab and pemetrexed chemotherapy. Following identification of a mutation of the echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) gene, crizotinib was then administered as targeted treatment. Kidney function was normal at diagnosis and during the first line therapy. The administration of crizotinib coincided on two occasions with a conspicuous rise in the serum creatinine level. Urinary protein over creatinine ratio was 0.31 g/g with 22% albumin and macroscopic hematuria. A kidney biopsy was performed at the time of the second episode of renal impairment which showed acute tubular necrosis (ATN) indicating recent renal injury together with a mononuclear cell infiltrate consistent with ongoing repair related to a previous insult. The renal lesions were closely related temporally to crizotinib administration, supporting a causative role for crizotinib in the acute renal injury and this phenomenon has not previously been described.
authors.affiliation: Medical Oncology Department, CAL, University Hospital, Nice, France.
authors.forename: Lauris
authors.initials: L
authors.lastname: Gastaud
authors.forename: Damien
authors.initials: D
authors.lastname: Ambrosetti
authors.forename: Josiane
authors.initials: J
authors.lastname: Otto
authors.forename: Charles-Hugo
authors.initials: CH
authors.lastname: Marquette
authors.forename: Michael
authors.initials: M
authors.lastname: Coutts
authors.forename: Paul
authors.initials: P
authors.lastname: Hofman
authors.forename: Vincent
authors.initials: V
authors.lastname: Esnault
authors.forename: Guillaume
authors.initials: G
authors.lastname: Favre
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000473:pathology; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications* / Q000188:drug therapy; D000077547:Crizotinib; D017809:Fatal Outcome; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011720:Pyrazoles / Q000009:adverse effects* / Q000627:therapeutic use; D011725:Pyridines / Q000009:adverse effects* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib
keywords: Acute kidney injury; Acute tubular necrosis; Adverse drug reaction; Chemotherapy; Crizotinib; EML4-ALK protein; Non-small-cell lung carcinoma; Tyrosine kinase inhibitor