title: Serotonin-Norepinephrine Reuptake Inhibitors and the Risk of AKI: A Cohort Study of Eight Administrative Databases and Meta-Analysis.
abstract: OBJECTIVE
  A safety signal regarding cases of AKI after exposure to serotonin-norepinephrine reuptake inhibitors (SNRIs) was identified by Health Canada. Therefore, this study assessed whether the use of SNRIs increases the risk of AKI compared with selective serotonin reuptake inhibitors (SSRIs) and examined the risk associated with each individual SNRI.
  
  
  METHODS
  Multiple retrospective population-based cohort studies were conducted within eight administrative databases from Canada, the United States, and the United Kingdom between January 1997 and March 2010. Within each cohort, a nested case-control analysis was performed to estimate incidence rate ratios (RRs) of AKI associated with SNRIs compared with SSRIs using conditional logistic regression, with adjustment for high-dimensional propensity scores. The overall effect across sites was estimated using meta-analytic methods.
  
  
  RESULTS
  There were 38,974 cases of AKI matched to 384,034 controls. Current use of SNRIs was not associated with a higher risk of AKI compared with SSRIs (fixed-effect RR, 0.97; 95% confidence interval [95% CI], 0.94 to 1.01). Current use of venlafaxine and desvenlafaxine considered together was not associated with a higher risk of AKI (RR, 0.96; 95% CI, 0.92 to 1.00). For current use of duloxetine, there was significant heterogeneity among site-specific estimates such that a random-effects meta-analysis was performed showing a 16% higher risk, although this risk was not statistically significant (RR, 1.16; 95% CI, 0.96 to 1.40). This result is compatible with residual confounding, because there was a substantial imbalance in the prevalence of diabetes between users of duloxetine and users of others SNRIs or SSRIs. After further adjustment by including diabetes as a covariate in the model along with propensity scores, the fixed-effect RR was 1.02 (95% CI, 0.95 to 1.10).
  
  
  CONCLUSIONS
  There is no evidence that use of SNRIs is associated with a higher risk of hospitalization for AKI compared with SSRIs.
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Christel
authors.initials: C
authors.lastname: Renoux
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Lix
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Valérie
authors.initials: V
authors.lastname: Patenaude
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Bresee
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Paterson
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Lafrance
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Hala
authors.initials: H
authors.lastname: Tamim
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Salaheddin M
authors.initials: SM
authors.lastname: Mahmud
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Mhd Wasem
authors.initials: MW
authors.lastname: Alsabbagh
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Brenda
authors.initials: B
authors.lastname: Hemmelgarn
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Colin R
authors.initials: CR
authors.lastname: Dormuth
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material. pierre.ernst@mcgill.ca.
authors.forename: Pierre
authors.initials: P
authors.lastname: Ernst
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000453:epidemiology; D000293:Adolescent; D000328:Adult; D000368:Aged; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D002648:Child; D016208:Databases, Factual; D000069468:Desvenlafaxine Succinate / Q000009:adverse effects / Q000627:therapeutic use; D000068736:Duloxetine Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006113:United Kingdom / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D000069470:Venlafaxine Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000069468:Desvenlafaxine Succinate; D000068736:Duloxetine Hydrochloride; D017367:Selective Serotonin Reuptake Inhibitors; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride
keywords: ARF; clinical epidemiology; depression; drug nephrotoxicity; risk factors