title: An elevated pro-inflammatory cytokine response is linked to development of amphotericin B-induced nephrotoxicity.
abstract: OBJECTIVE
  The underlying mechanism for amphotericin B-induced acute kidney injury (AKI) remains poorly understood and may be immunologically mediated. We assessed whether the development of nephrotoxicity is linked to a distinct cytokine profile in patients receiving amphotericin B deoxycholate (AmBD).
  
  
  METHODS
  In 58 patients who received AmBD, circulating serum interleukin (IL)-6, IL-8 and IL-10 were measured at baseline, week 1 and week 2 of antifungal treatment and correlated to the development of renal impairment. The Cox proportional hazards model approach was adopted for analysis.
  
  
  RESULTS
  The P value was 0.026 for the overall effect of IL-6 on time to development of AKI. An increasing or non-receding IL-6 trend by week 1 of AmBD treatment (followed by a decreasing or non-receding IL-6 trend from week 1 to week 2) correlated with an increased likelihood of nephrotoxicity [hazard ratio (HR) 6.93, P value 0.005 and HR 3.46, P value 0.035, respectively]. Similarly, persistently increasing IL-8 levels were linked to a 3.84-fold increased likelihood of AKI.
  
  
  CONCLUSIONS
  In patients receiving AmBD, persistence of an elevated pro-inflammatory cytokine milieu is associated with a predisposition to drug-related kidney injury.
authors.affiliation: Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Louis Y A
authors.initials: LY
authors.lastname: Chai
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Bee Choo
authors.initials: BC
authors.lastname: Tai
authors.forename: Lay Wai
authors.initials: LW
authors.lastname: Khin
authors.forename: Alieke G
authors.initials: AG
authors.lastname: Vonk
authors.forename: Boon Wee
authors.initials: BW
authors.lastname: Teo
authors.forename: Haran T
authors.initials: HT
authors.lastname: Schlamm
authors.forename: Raoul
authors.initials: R
authors.lastname: Herbrecht
authors.forename: J Peter
authors.initials: JP
authors.lastname: Donnelly
authors.forename: Peter F
authors.initials: PF
authors.lastname: Troke
authors.forename: Bart-Jan
authors.initials: BJ
authors.lastname: Kullberg
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000276:immunology*; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D016209:Interleukin-8 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D044967:Serum / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D016753:Interleukin-10; D000666:Amphotericin B
keywords: acute kidney injury; drug induced; immune responses; interleukins