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Acetaminophen administration and the risk of acute kidney injury: a self-controlled case series study

Authors Hiragi S, Yamada H, Tsukamoto T, Yoshida K, Kondo N, Matsubara T, Yanagita M, Tamura H, Kuroda T

Received 28 November 2017

Accepted for publication 24 January 2018

Published 6 March 2018 Volume 2018:10 Pages 265—276


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Irene Petersen

Shusuke Hiragi,1,2 Hiroyuki Yamada,1 Tatsuo Tsukamoto,1,3 Kazuki Yoshida,4,5 Naoya Kondo,1 Takeshi Matsubara,1 Motoko Yanagita,1 Hiroshi Tamura,2 Tomohiro Kuroda2

1Department of Nephrology, Graduate School of Medicine, Kyoto University, 2Division of Medical Informatics and Administration Planning, Kyoto University Hospital, Kyoto, 3Department of Nephrology and Dialysis, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan; 4Department of Epidemiology, 5Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA

Background: Acetaminophen (APAP) is frequently used for analgesia and is considered safer than nonsteroidal anti-inflammatory drugs (NSAIDs) for the kidneys. However, there is little epidemiological evidence of the association between APAP and acute kidney injury (AKI).
Objectives: To examine the association between APAP and AKI using the self-controlled case series (SCCS) method, which is a novel strategy to control between-person confounders by comparing the risk and reference periods in each patient.
Methods: We performed SCCS in 1,871 patients (39.9% female) who were administered APAP and subsequently developed AKI, by reviewing electronically stored hospital information system data from May 2011 to July 2016. We used conditional Poisson regression to compare each patient’s risk and reference period. As a time-varying confounder, we adjusted the status of liver and kidney functions, systemic inflammation, and exposure to NSAIDs.
Results: We identified 5,650 AKI events during the 260,549 person-day observation period. The unadjusted incidences during the reference and exposure periods were 2.01/100 and 3.12/100 person-days, respectively. The incidence rate ratio adjusted with SCCS was 1.03 (95% confidence interval [CI]: 0.95–1.12). When we restricted endpoints as stage 2 AKI- and stage 3 AKI-level creatinine elevations, the incidence rate ratios were 1.20 (95% CI 0.91–1.58) and 1.20 (95% CI 0.62–2.31), respectively, neither of which was statistically significant.
Conclusion: Our findings added epidemiological information for the relationship between APAP administration and AKI development. The results indicated scarce association between APAP and AKI, presumably supporting the general physicians’ impression that APAP is safer for kidney.

acetaminophen, acute kidney injury, adverse drug event, self-controlled case series, hospital information system

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