title: Targeting the Opioid Pathway for Uremic Pruritus: A Systematic Review and Meta-analysis.
abstract: BACKGROUND
  Patients undergoing hemodialysis or peritoneal dialysis often experience pruritus which is associated with morbidity and mortality. One proposed treatment approach is to target the opioid pathway using either µ-opioid antagonists or κ-opioid agonists.
  
  
  OBJECTIVE
  To review the efficacy of targeting the opioid pathway for pruritus among dialysis patients (uremic pruritus).
  
  
  METHODS
  Systematic review and meta-analysis.
  
  
  METHODS
  The systematic review included randomized controlled and randomized crossover trials identified in the MEDLINE, EMBASE, and Cochrane databases (1990 to June 2014) evaluating the efficacy of µ-opioid antagonists or κ-opioid agonists in the treatment of uremic pruritus.
  
  
  METHODS
  Adult (≥18 years) chronic dialysis patients.
  
  
  METHODS
  The primary outcome being evaluated was reduction in itch severity measured on a patient-reported visual analog scale (VAS).
  
  
  RESULTS
  Five studies out of 3587 screened articles met the inclusion criteria. Three studies evaluated the efficacy of naltrexone, a µ-opioid antagonist, and 2 studies evaluated the efficacy of nalfurafine, a κ-opioid agonist. Duration of included studies was short, ranging from 2 to 9 weeks.
  
  
  CONCLUSIONS
  Due to the heterogeneity in reporting of outcomes, data from the studies evaluating naltrexone could not be pooled. Pooled analysis, using a random effects model, found that use of nalfurafine resulted in a 9.50 mm (95% confidence interval [CI], 6.27-12.74,P< .001) greater reduction of itch severity (measured on a 100-mm VAS) than placebo in the treatment of uremic pruritus.
  
  
  CONCLUSIONS
  Nalfurafine holds some promise with respect to the treatment of uremic pruritus among dialysis patients. However, more long-term randomized controlled trials evaluating the efficacy of therapies targeting the opioid pathway for uremic pruritus are required.
authors.affiliation: Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Deep
authors.initials: D
authors.lastname: Jaiswal
authors.affiliation: Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Drea
authors.initials: D
authors.lastname: Uzans
authors.affiliation: Department of Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Jill
authors.initials: J
authors.lastname: Hayden
authors.affiliation: Dalhousie University, Halifax, Nova Scotia, Canada; Division of Nephrology, Department of Medicine, Nova Scotia Health, Halifax, Canada.
authors.forename: Bryce A
authors.initials: BA
authors.lastname: Kiberd
authors.affiliation: Dalhousie University, Halifax, Nova Scotia, Canada; Division of Nephrology, Department of Medicine, Nova Scotia Health, Halifax, Canada.
authors.forename: Karthik K
authors.initials: KK
authors.lastname: Tennankore
keywords: dialysis; nalfurafine; uremic pruritus; κ-opioid agonist