title: New insights into renal toxicity of the B-RAF inhibitor, vemurafenib, in patients with metastatic melanoma.
abstract: OBJECTIVE
  Vemurafenib (VMF) is a B-RAF inhibitor used in the treatment of B-RAF-V600-mutant metastatic melanomas. Reports of acute kidney injury (AKI) in patients treated with VMF are scarce.
  
  
  METHODS
  To investigate the incidence and severity of AKI, we conducted a retrospective, observational, monocentric study in the Lyon Sud Hospital University, France, which included 74 patients with metastatic B-RAF-mutated melanomas treated with VMF, between June 2011 and August 2014. According to the Kidney Disease Improving Global Outcomes Guidelines, AKI is defined as an increase in serum creatinine concentration exceeding the baseline concentration by 1.5 fold. Serum creatinine was thus determined before treatment, on a monthly basis during treatment, and 3 months after treatment discontinuation. Patients were divided into two main groups: AKI-positive (AKI+) and AKI-negative (AKI-) and further subdivided into three groups according to AKI severity (stage 1, 2 or 3). To visualize the tissue damage caused by VMF, kidney biopsies were performed for two stage 1 AKI+ patients.
  
  
  RESULTS
  Of the 74 patients, 30 (40.5 %) were AKI-, and of the 44 AKI+ patients (59.5 %), 29 (66 %) were diagnosed within the first three months of treatment. There were significantly more men in the AKI+ group: n = 33 (75 %) versus n = 12 (40 %) women, p = 0.004 with an odds ratio for developing AKI of 4.6 (95 % CI 1.48-14.23). Most AKI + cases were considered as stage 1 (n = 40; 91 %) and the remaining four (9 %) as stage 2 AKI. Kidney biopsies revealed interstitial fibrosis and acute focal tubular damage. However, renal failure was reversible in 80 % of patients within 3 months of VMF discontinuation.
  
  
  CONCLUSIONS
  We observed frequent, reversible, moderately severe AKI with some histological evidence of tubular and interstitial damage in VMF-treated patients, suggesting that renal function should be carefully monitored in male patients, especially during the first 3 months.
authors.affiliation: Department of Nephrology, Centre Hospitalier Lyon Sud, 165, Chemin du Grand Revoyet, 69495, Pierre Bénite, France. cecile.teuma@hotmail.fr.|UCBL, INSERM, Université de Lyon, Lyon, France. cecile.teuma@hotmail.fr.
authors.forename: Cécile
authors.identifier: http://orcid.org/0000-0002-8903-1895
authors.initials: C
authors.lastname: Teuma
authors.affiliation: Department of Dermatology, Centre Hospitalier Lyon Sud, 69495, Pierre Bénite, France.|Centre de Recherche en Cancérologie de Lyon, Lyon, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Perier-Muzet
authors.affiliation: Department of Nephrology, Centre Hospitalier Lyon Sud, 165, Chemin du Grand Revoyet, 69495, Pierre Bénite, France.|UCBL, INSERM, Université de Lyon, Lyon, France.
authors.forename: Solenne
authors.initials: S
authors.lastname: Pelletier
authors.affiliation: Department of Nephrology, Centre Hospitalier Lyon Sud, 165, Chemin du Grand Revoyet, 69495, Pierre Bénite, France.|UCBL, INSERM, Université de Lyon, Lyon, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Nouvier
authors.affiliation: Department of Dermatology, Centre Hospitalier Lyon Sud, 69495, Pierre Bénite, France.|Centre de Recherche en Cancérologie de Lyon, Lyon, France.
authors.forename: Mona
authors.initials: M
authors.lastname: Amini-Adl
authors.affiliation: Department of Nephrology, Centre Hospitalier Lyon Sud, 165, Chemin du Grand Revoyet, 69495, Pierre Bénite, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Dijoud
authors.affiliation: Department of Dermatology, Centre Hospitalier Lyon Sud, 69495, Pierre Bénite, France.|Centre de Recherche en Cancérologie de Lyon, Lyon, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Duru
authors.affiliation: Department of Dermatology, Centre Hospitalier Lyon Sud, 69495, Pierre Bénite, France.|Centre de Recherche en Cancérologie de Lyon, Lyon, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Thomas
authors.affiliation: Department of Nephrology, Centre Hospitalier Lyon Sud, 165, Chemin du Grand Revoyet, 69495, Pierre Bénite, France.|UCBL, INSERM, Université de Lyon, Lyon, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Fouque
authors.affiliation: Department of Nephrology, Centre Hospitalier Lyon Sud, 165, Chemin du Grand Revoyet, 69495, Pierre Bénite, France.|UCBL, INSERM, Université de Lyon, Lyon, France.
authors.forename: Maurice
authors.initials: M
authors.lastname: Laville
authors.affiliation: Department of Dermatology, Centre Hospitalier Lyon Sud, 69495, Pierre Bénite, France.|Centre de Recherche en Cancérologie de Lyon, Lyon, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Dalle
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D005260:Female; D005602:France; D006801:Humans; D015994:Incidence; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors; D000077484:Vemurafenib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; D003404:Creatinine; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF inhibitor; Kidney failure; Metastatic melanoma; Vemurafenib