Proton pump inhibitors and traditional nonsteroidal anti-inflammatory drugs and the risk of acute interstitial nephritis and acute kidney injury

Authors

  • Charles E. Leonard,

    Corresponding author
    1. Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
    • Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
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  • Cristin P. Freeman,

    1. Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
    2. Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
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  • Craig W. Newcomb,

    1. Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
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  • Peter P. Reese,

    1. Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
    2. Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
    3. Renal, Electrolyte, and Hypertension Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
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  • Maximilian Herlim,

    1. Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
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  • Warren B. Bilker,

    1. Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
    2. Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
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  • Sean Hennessy,

    1. Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
    2. Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
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  • Brian L. Strom

    1. Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
    2. Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
    3. Division of General Internal Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
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  • This research was presented in abstract form at the 28th International Conference on Pharmacoepidemiology and Therapeutic Risk Management (Barcelona, Spain) on August 25, 2012.
  • This article was published online on August 09, 2012. Error was subsequently identified. This notice is included in the online and print versions to indicate that both have been corrected [September 19, 2012].

Charles E. Leonard, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, 834 Blockley Hall/423 Guardian Drive, Philadelphia, PA, USA. E-mail: celeonar@mail.med.upenn.edu

ABSTRACT

Purpose

This study aims to examine the associations between proton pump inhibitors (PPIs), traditional nonsteroidal anti-inflammatory drugs (tNSAIDs), PPI + tNSAID co-exposure, and the development of the following: (i) acute interstitial nephritis (AIN), a specific kidney injury often attributed to these drugs, and (ii) acute kidney injury (AKI), a general kidney injury encompassing AIN.

Methods

Two retrospective case–control studies were conducted, one for each outcome, within the General Practice Research Database. Cases were diagnostic-coded AIN (primary outcome) or AKI (secondary outcome) events. Controls were matched on age, sex, and general practitioner practice. Exposures were defined by the presence/absence of the following mutually exclusive therapies on the index date: (i) PPI alone; (ii) tNSAID alone; (iii) PPI + tNSAID; or (iv) neither PPI nor tNSAID (referent).

Results

Sixty-eight AIN cases and 3347 controls were identified. The adjusted odds ratios (ORs) for PPI and tNSAID exposures alone were 3.20 (0.80–12.79) and 1.90 (0.65–5.51), respectively. Numerous sensitivity analyses produced adjusted ORs for AIN between 3.0 and 7.7, and 1.6 and 1.9, respectively. We identified 27 982 AKI cases and 1 323 850 controls. The adjusted ORs for PPI alone, tNSAID alone, and PPI + tNSAID exposures were 1.05 (0.97–1.14), 1.31 (1.25–1.37), and 1.33 (1.07–1.64), respectively. Numerous sensitivity analyses produced adjusted ORs for AKI between 1.0 and 1.1, 1.1 and 1.3, and 1.3 and 1.4, respectively.

Conclusions

Proton pump inhibitor exposure may increase the odds of AIN, but this result was not definitive and should be confirmed in a dataset with more AIN cases to allow for increased statistical precision. tNSAIDs, yet not PPIs, were associated with a significantly increased odds of AKI. Copyright © 2012 John Wiley & Sons, Ltd.

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