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

Abstract

BackgroundAcetaminophen (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).ObjectivesTo 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.MethodsWe 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.ResultsWe 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.ConclusionOur 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.

Toxicological Property of Acetaminophen: The Dark Side of a Safe Antipyretic/Analgesic Drug?

“…In a cohort study in subjects with normal renal function, the relative risk of renal failure was significantly lower in APAP group than NSAIDs. 23) Hiragi et al 24) first reported epidemiological evidence for an association between APAP administration and AKI development using self-controlled case series method. They concluded that the results presumably support the general clinicians' impression that APAP is safer for the kidney than NSAIDs.…”

Roles of Hydrogen Sulfide Donors in Common Kidney Diseases

“…APAP/paracetamol-induced nephrotoxicity is amongst the least causatives of renal injury (Hiragi et al, 2018). The overdose of paracetamol is associated with elevated serum levels of creatinine and urea, oxidative stress (Canayakin et al, 2016), apoptosis, and DNA damage (Lorz et al, 2004).…”

“…The enzymatic production of H 2 S involves two systems, including pyridoxal 5′-phosphate-dependent (CBS and CSE) and pyridoxal 5′-phosphate-independent (3-MPST) systems ( Stipanuk and Beck, 1982 ; Mikami et al, 2011 ). CBS mediates the conversion of Hcy and serine to produce cystathionine, which is then converted by CSE into Cys, α-ketobutyrate, and ammonia ( Stipanuk and Ueki, 2011 ). CBS facilitates β replacement of thiol (-SH) group of the Cys with Hcy to produce H 2 S; meanwhile, CSE facilitates α, β, and γ elimination of cystathionine, Hcy, and Cys to form H 2 S ( Chiku et al, 2009 ).…”

Analgesic therapy and a problem of comorbidity

“…Недавно были представлены данные крупного популяционного исследования S. Hiragi и соавт. [35], в котором изучалась связь между использованием ПАР и развитием 5650 случаев острой почечной недостаточности (ОПН). Отношение инцидентов ОПН для ПАР составило 1,03 (95% ДИ 0,95-1,12), что указывает на отсутствие риска при использовании данного препарата.…”