Increased Risk of End-Stage Renal Disease (ESRD) Requiring Chronic Dialysis is Associated With Use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

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Abstract

It is known that many medical adverse events can be caused by nonsteroidal anti-inflammatory drugs (NSAIDs); however, epidemiologic evidence has not granted an affirmative relationship between NSAID use and the risk of end-stage renal disease (ESRD). We aimed to investigate the relationship in a Chinese population between short-term NSAID use and development of ESRD requiring chronic dialysis.

A retrospective case-crossover design was used in this study. Using the Taiwanese National Health Insurance database, we identified 109,400 incident chronic ESRD patients with dialysis initiation from 1998 to 2009. For each patient, we defined the case period as 1 to 14 days and the control period as 105 to 118 days, respectively, before the first dialysis date. The washout period was 90 days between the case and control period. Detailed information about NSAID use was compared between the case and control periods. We calculated odds ratios (ORs) and their 95% confidence intervals (CIs) using a conditional logistic regression model.

NSAID use was found to be a significant risk factor associated with dialysis commencement. The adjusted OR was 2.73 (95% CI: 2.62–2.84) for nonselective NSAIDs and 2.17 (95% CI: 1.83–2.57) for celecoxib. The OR reached 3.05 for the use of acetic acid derivatives. Compared with the oral forms, significantly higher risks were seen in parenteral NSAID use (OR: 8.66, 95% CI: 6.12–20.19).

NSAIDs should be prescribed with caution, especially for those in ESRD high-risk groups.

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Most cited references 32

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Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs.

T Perneger, Seamus P. Whelton, M Klag (1994)

People who take analgesic drugs frequently may be at increased risk of end-stage renal disease (ESRD), but the extent of this risk remains unclear. We studied 716 patients treated for ESRD and 361 control subjects of similar age from Maryland, Virginia, West Virginia, and Washington, D.C. The study participants were interviewed by telephone about their past use of medications containing acetaminophen, aspirin, and other nonsteroidal antiinflammatory drugs (NSAIDs). For each analgesic drug, the average use (in pills per year) and the cumulative intake (in pills) were examined for any association with ESRD. Heavier acetaminophen use was associated with an increased risk of ESRD in a dose-dependent fashion. When persons who took an average of 0 to 104 pills per year were used for reference, the odds ratio of ESRD was 1.4 (95 percent confidence interval, 0.8 to 2.4) for those who took 105 to 365 pills per year and 2.1 (95 percent confidence interval, 1.1 to 3.7) for those who took 366 or more pills per year, after adjustment for race, sex, age, and intake of other analgesic drugs. When persons who had taken fewer than 1000 pills containing acetaminophen in their lifetime were used for reference, the odds ratio was 2.0 (95 percent confidence interval, 1.3 to 3.2) for those who had taken 1000 to 4999 pills and 2.4 (95 percent confidence interval, 1.2 to 4.8) for those who had taken 5000 or more pills. Approximately 8 to 10 percent of the overall incidence of ESRD was attributable to acetaminophen use. A cumulative dose of 5000 or more pills containing NSAIDs was also associated with an increased odds of ESRD (odds ratio, 8.8), but the use of aspirin was not. People who often take acetaminophen or NSAIDs have an increased risk of ESRD, but not those who often take aspirin.

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Nonsteroidal anti-inflammatory drugs and risk of ARF in the general population.

Cristina Varas-Lorenzo, Consuelo Huerta, Jordi Castellsague … (2005)

Most epidemiological studies evaluating the association between nonsteroidal anti-inflammatory drugs (NSAIDs) and acute renal failure (ARF) found an increased risk for developing ARF while taking NSAIDs. Despite these studies, little is known about the effect of dose and duration of therapy, risk of individual NSAIDs, comorbidity, or concomitant use of other nephrotoxic drugs. This is a nested case-control study using the General Practice Research Database from the United Kingdom. Participants were 386,916 patients aged 50 to 84 years on January 1, 1997, and free of known cancer, renal disorder, cirrhosis, or systemic connective tissue disease. After validation of cases identified from this cohort, 103 patients were confirmed as idiopathic cases of ARF and compared with 5,000 controls frequency matched by age and sex. Current users of NSAIDs had a relative risk (RR) for ARF of 3.2 (95% confidence interval [CI], 1.8 to 5.8), and the risk declined after treatment was discontinued. Increased risk was present with both short- and long-term therapy and was slightly greater among users of high doses. History of heart failure (HF), hypertension, diabetes, and hospitalizations and consultant visits in the previous year were all associated with a greater risk for ARF. There was a suggestion of a modification of the effect of NSAIDs in patients with hypertension and those with HF. Use of selected cardiovascular drugs was associated with a 5-fold increase in risk for ARF. Diuretics presented the greatest risk. Risk increased with concomitant use of NSAIDs and diuretics (RR, 11.6; 95% CI, 4.2 to 32.2) and NSAIDs and calcium channel blockers (RR, 7.8; 95% CI, 3.0 to 20.5). NSAID users had a 3-fold greater risk for developing a first-ever diagnosis of clinical ARF compared with non-NSAID users in the general population. NSAIDs should be used with special caution in patients with hypertension and/or HF.

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When should case-only designs be used for safety monitoring of medical products?

Andrew Nelson, Malcolm Maclure, Hong-Wei Hua … (2011)

To assess case-only designs for surveillance with administrative databases. We reviewed literature on two designs that are observational analogs to crossover experiments: the self-controlled case series (SCCS) and the case-crossover (CCO) design. SCCS views the 'experiment' prospectively, comparing outcome risks in windows with different exposures. CCO retrospectively compares exposure frequencies in case and control windows. The main strength of case-only designs is they entail self-controlled analyses that eliminate confounding and selection bias by time-invariant characteristics not recorded in healthcare databases. They also protect privacy and are computationally efficient, as they require fewer subjects and variables. They are better than cohort designs for investigating transient effects of accurately recorded preventive agents, for example, vaccines. They are problematic if timing of self-administration is sporadic and dissociated from dispensing times, for example, analgesics. They tend to have less exposure misclassification bias and time-varying confounding if exposures are brief. Standard SCCS designs are bidirectional (using time both before and after the first exposure event), so they are more susceptible than CCOs to reverse-causality bias, including immortal-time bias. This is true also for sequence symmetry analysis, a simplified SCCS. Unidirectional CCOs use only time before the outcome, so they are less affected by reverse causality but susceptible to exposure-trend bias. Modifications of SCCS and CCO partially deal with these biases. The head-to-head comparison of multiple products helps to control residual biases. The case-only analyses of intermittent users complement the cohort analyses of prolonged users because their different biases compensate for one another. Copyright © 2012 John Wiley & Sons, Ltd.

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Author and article information

Journal

Journal ID (nlm-ta): Medicine (Baltimore)

Journal ID (iso-abbrev): Medicine (Baltimore)

Journal ID (publisher-id): MEDI

Title: Medicine

Publisher: Wolters Kluwer Health

ISSN (Print): 0025-7974

ISSN (Electronic): 1536-5964

Publication date Collection: September 2015

Publication date (Electronic): 25 September 2015

Volume: 94

Issue: 38

Electronic Location Identifier: e1362

Affiliations

From the Institute of Population Health Sciences, National Health Research Institutes, Zhunan (Y-KC, J-SL, C-CH); Department of Health Services Administration, China Medical University, Taichung (C-CH); Division of Nephrology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi (Y-HH); Department of Nursing, Min-Hwei Junior College of Health Care Management, Tainan (Y-HH); Institutes of Physiology and Clinical Medicine, National Yang-Ming University (D-CT); Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital (D-CT); and Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan (D-CT, C-CH).

Author notes

Correspondence: Chih-Cheng Hsu, Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan (e-mail: cch@ 123456nhri.org.tw ).

Article

Accession ID: 01362

DOI: 10.1097/MD.0000000000001362

PMC ID: 4635740

PubMed ID: 26402800

SO-VID: 8e412599-82f8-43e9-8578-7f48f4a15582

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This is an open access article distributed under the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

History

Date received : 15 May 2015

Date revision received : 8 July 2015

Date accepted : 18 July 2015

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Increased Risk of End-Stage Renal Disease (ESRD) Requiring Chronic Dialysis is Associated With Use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) : Nationwide Case-Crossover Study

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Most cited references 32

Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs.

Nonsteroidal anti-inflammatory drugs and risk of ARF in the general population.

When should case-only designs be used for safety monitoring of medical products?

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