Serotonin-norepinephrine reuptake inhibitors and the risk of AKI

A cohort study of eight administrative databases and meta-analysis

Christel Renoux, Lisa M. Lix, Valérie Patenaude, Lauren C. Bresee, J. Michael Paterson, Jean Philippe Lafrance, Hala Tamim, Salaheddin M. Mahmud, Mhd Wasem Alsabbagh, Brenda R. Hemmelgarn, Colin R. Dormuth, Ernst Pierre, Samy Suissa, Gary F. Teare, Patricia J. Martens, Patricia Caetano, David A. Henry, Jacques LeLorier, Adrian R. Levy, Pierre Ernst* & 3 others Robert W. Platt, Ingrid S. Sketris, Canadian Network of Observational Drug Effect Studies (CNODES)

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

Background and objectives 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. Design, setting, participants, & measurements 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 togetherwas not associatedwith 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 sitespecific 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.

Original languageEnglish
Pages (from-to)1716-1722
Number of pages7
JournalClinical Journal of the American Society of Nephrology
Volume10
Issue number10
DOIs
Publication statusPublished - 7 Oct 2015
Externally publishedYes

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Meta-Analysis
Cohort Studies
Serotonin Uptake Inhibitors
Databases
Propensity Score
Confidence Intervals
Canada
Serotonin and Noradrenaline Reuptake Inhibitors
Hospitalization
Logistic Models
Safety
Incidence
Health
Population

Cite this

Renoux, C., Lix, L. M., Patenaude, V., Bresee, L. C., Paterson, J. M., Lafrance, J. P., ... Canadian Network of Observational Drug Effect Studies (CNODES) (2015). Serotonin-norepinephrine reuptake inhibitors and the risk of AKI: A cohort study of eight administrative databases and meta-analysis. Clinical Journal of the American Society of Nephrology, 10(10), 1716-1722. https://doi.org/10.2215/CJN.11271114
Renoux, Christel ; Lix, Lisa M. ; Patenaude, Valérie ; Bresee, Lauren C. ; Paterson, J. Michael ; Lafrance, Jean Philippe ; Tamim, Hala ; Mahmud, Salaheddin M. ; Alsabbagh, Mhd Wasem ; Hemmelgarn, Brenda R. ; Dormuth, Colin R. ; Pierre, Ernst ; Suissa, Samy ; Teare, Gary F. ; Martens, Patricia J. ; Caetano, Patricia ; Henry, David A. ; LeLorier, Jacques ; Levy, Adrian R. ; Ernst, Pierre ; Platt, Robert W. ; Sketris, Ingrid S. ; Canadian Network of Observational Drug Effect Studies (CNODES). / Serotonin-norepinephrine reuptake inhibitors and the risk of AKI : A cohort study of eight administrative databases and meta-analysis. In: Clinical Journal of the American Society of Nephrology. 2015 ; Vol. 10, No. 10. pp. 1716-1722.
@article{9de888a7e98a40f2b2f63e9a4b026d8a,
title = "Serotonin-norepinephrine reuptake inhibitors and the risk of AKI: A cohort study of eight administrative databases and meta-analysis",
abstract = "Background and objectives 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. Design, setting, participants, & measurements 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 togetherwas not associatedwith 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 sitespecific 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.",
author = "Christel Renoux and Lix, {Lisa M.} and Val{\'e}rie Patenaude and Bresee, {Lauren C.} and Paterson, {J. Michael} and Lafrance, {Jean Philippe} and Hala Tamim and Mahmud, {Salaheddin M.} and Alsabbagh, {Mhd Wasem} and Hemmelgarn, {Brenda R.} and Dormuth, {Colin R.} and Ernst Pierre and Samy Suissa and Teare, {Gary F.} and Martens, {Patricia J.} and Patricia Caetano and Henry, {David A.} and Jacques LeLorier and Levy, {Adrian R.} and Pierre Ernst and Platt, {Robert W.} and Sketris, {Ingrid S.} and {Canadian Network of Observational Drug Effect Studies (CNODES)}",
year = "2015",
month = "10",
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doi = "10.2215/CJN.11271114",
language = "English",
volume = "10",
pages = "1716--1722",
journal = "Clinical journal of the American Society of Nephrology : CJASN",
issn = "1555-9041",
publisher = "AMER SOC NEPHROLOGY",
number = "10",

}

Renoux, C, Lix, LM, Patenaude, V, Bresee, LC, Paterson, JM, Lafrance, JP, Tamim, H, Mahmud, SM, Alsabbagh, MW, Hemmelgarn, BR, Dormuth, CR, Pierre, E, Suissa, S, Teare, GF, Martens, PJ, Caetano, P, Henry, DA, LeLorier, J, Levy, AR, Ernst, P, Platt, RW, Sketris, IS & Canadian Network of Observational Drug Effect Studies (CNODES) 2015, 'Serotonin-norepinephrine reuptake inhibitors and the risk of AKI: A cohort study of eight administrative databases and meta-analysis', Clinical Journal of the American Society of Nephrology, vol. 10, no. 10, pp. 1716-1722. https://doi.org/10.2215/CJN.11271114

Serotonin-norepinephrine reuptake inhibitors and the risk of AKI : A cohort study of eight administrative databases and meta-analysis. / Renoux, Christel; Lix, Lisa M.; Patenaude, Valérie; Bresee, Lauren C.; Paterson, J. Michael; Lafrance, Jean Philippe; Tamim, Hala; Mahmud, Salaheddin M.; Alsabbagh, Mhd Wasem; Hemmelgarn, Brenda R.; Dormuth, Colin R.; Pierre, Ernst; Suissa, Samy; Teare, Gary F.; Martens, Patricia J.; Caetano, Patricia; Henry, David A.; LeLorier, Jacques; Levy, Adrian R.; Ernst, Pierre; Platt, Robert W.; Sketris, Ingrid S.; Canadian Network of Observational Drug Effect Studies (CNODES).

In: Clinical Journal of the American Society of Nephrology, Vol. 10, No. 10, 07.10.2015, p. 1716-1722.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Serotonin-norepinephrine reuptake inhibitors and the risk of AKI

T2 - A cohort study of eight administrative databases and meta-analysis

AU - Renoux, Christel

AU - Lix, Lisa M.

AU - Patenaude, Valérie

AU - Bresee, Lauren C.

AU - Paterson, J. Michael

AU - Lafrance, Jean Philippe

AU - Tamim, Hala

AU - Mahmud, Salaheddin M.

AU - Alsabbagh, Mhd Wasem

AU - Hemmelgarn, Brenda R.

AU - Dormuth, Colin R.

AU - Pierre, Ernst

AU - Suissa, Samy

AU - Teare, Gary F.

AU - Martens, Patricia J.

AU - Caetano, Patricia

AU - Henry, David A.

AU - LeLorier, Jacques

AU - Levy, Adrian R.

AU - Ernst, Pierre

AU - Platt, Robert W.

AU - Sketris, Ingrid S.

AU - Canadian Network of Observational Drug Effect Studies (CNODES)

PY - 2015/10/7

Y1 - 2015/10/7

N2 - Background and objectives 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. Design, setting, participants, & measurements 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 togetherwas not associatedwith 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 sitespecific 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.

AB - Background and objectives 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. Design, setting, participants, & measurements 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 togetherwas not associatedwith 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 sitespecific 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.

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U2 - 10.2215/CJN.11271114

DO - 10.2215/CJN.11271114

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VL - 10

SP - 1716

EP - 1722

JO - Clinical journal of the American Society of Nephrology : CJASN

JF - Clinical journal of the American Society of Nephrology : CJASN

SN - 1555-9041

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