{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:27:10Z","timestamp":1790634430122,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2012,8,9]],"date-time":"2012-08-09T00:00:00Z","timestamp":1344470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>This study aims to examine the associations between proton pump inhibitors (PPIs), traditional nonsteroidal anti\u2010inflammatory drugs (tNSAIDs), PPI\u2009+\u2009tNSAID co\u2010exposure, 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two retrospective case\u2013control studies were conducted, one for each outcome, within the General Practice Research Database. Cases were diagnostic\u2010coded 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\u2009+\u2009tNSAID; or (iv) neither PPI nor tNSAID (referent).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixty\u2010eight AIN cases and 3347 controls were identified. The adjusted odds ratios (ORs) for PPI and tNSAID exposures alone were 3.20 (0.80\u201312.79) and 1.90 (0.65\u20135.51), 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\u2009982 AKI cases and 1\u2009323\u2009850 controls. The adjusted ORs for PPI alone, tNSAID alone, and PPI\u2009+\u2009tNSAID exposures were 1.05 (0.97\u20131.14), 1.31 (1.25\u20131.37), and 1.33 (1.07\u20131.64), 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Proton pump inhibitor exposure <jats:italic>may<\/jats:italic> 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 \u00a9 2012 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.3329","type":"journal-article","created":{"date-parts":[[2012,8,10]],"date-time":"2012-08-10T00:34:09Z","timestamp":1344558849000},"page":"1155-1172","source":"Crossref","is-referenced-by-count":83,"title":["Proton pump inhibitors and traditional nonsteroidal anti\u2010inflammatory drugs and the risk of acute interstitial nephritis and acute kidney injury"],"prefix":"10.1002","volume":"21","author":[{"given":"Charles E.","family":"Leonard","sequence":"first","affiliation":[{"name":"Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"},{"name":"Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristin P.","family":"Freeman","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"},{"name":"Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig W.","family":"Newcomb","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter P.","family":"Reese","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"},{"name":"Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"},{"name":"Renal, Electrolyte, and Hypertension Division Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Herlim","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren B.","family":"Bilker","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"},{"name":"Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Hennessy","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"},{"name":"Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Strom","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"},{"name":"Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"},{"name":"Division of General Internal Medicine Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,8,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2008.09.016"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39406.449456.BE"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/fampra\/18.3.333"},{"key":"e_1_2_7_5_1","unstructured":"IMS Health Report. 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