Original investigation: pathogenesis and treatment of kidney disease and hypertension
Analgesic use and change in kidney function in apparently healthy men1

https://doi.org/10.1016/S0272-6386(03)00647-4Get rights and content

Abstract

Background:

Studies using a single creatinine measurement have yielded inconsistent results regarding analgesic use and kidney function.

Methods:

This is a prospective cohort study of 4,494 US male physicians who provided blood samples in both 1982 and 1996. Outcomes measured were increase in plasma creatinine level of 0.3 mg/dL or greater (≥26.5 μmol/L) and decline in glomerular filtration rate (GFR) of 29.0 mL/min/1.73 m2 or greater during this 14-year period. Self-reported use of aspirin, acetaminophen, and other nonsteroidal anti-inflammatory drugs (NSAIDs) was classified as never (<12 pills during the study period), 12 to 1,499 pills, 1,500 to 2,499 pills, and 2,500 or greater pills during the study period.

Results:

Blood measurements made 14 years apart showed increased creatinine levels in 242 participants and decreased GFRs in 224 participants. Compared with never use, multivariable-adjusted odds ratios (ORs) of increased creatinine levels were 0.98 (95% confidence interval [CI], 0.43 to 2.23) for 2,500 or greater pills of aspirin, 1.02 (95% CI, 0.55 to 1.90) for 2,500 or greater pills of acetaminophen, and 1.12 (95% CI, 0.67 to 1.87) for 2,500 or greater pills of other NSAIDs. For decreased GFRs, ORs for intake of 2,500 or greater pills were 0.75 (95% CI, 0.35 to 1.57) for aspirin, 1.22 (95% CI, 0.66 to 2.26) for acetaminophen, and 1.11 (95% CI, 0.65 to 1.90) for other NSAIDs. Use of aspirin, but not acetaminophen or other NSAIDs, was associated with a reduced risk for change in kidney function in participants without cardiovascular risk factors and a possible but nonsignificant increase in those with cardiovascular risk factors.

Conclusion:

Occasional to moderate analgesic intake of aspirin, acetaminophen, or NSAIDs does not appear to increase the risk for decline in kidney function during a period of 14 years.

Section snippets

Methods

Study subjects were participants in the PHS, a completed randomized trial of aspirin and beta carotene in the primary prevention of cardiovascular disease and cancer. The design and methods of the PHS have been described in detail previously.23, 24, 25 The PHS included 22,071 apparently healthy male physicians without history of cardiovascular disease, cancer (except nonmelanoma skin cancer), current liver disease or kidney dysfunction (defined as kidney failure or insufficiency), or other

Results

Among 4,494 men with creatinine measurements in 1982 and 1996 and no history of kidney failure or kidney insufficiency at baseline or during follow-up, an increase in plasma creatinine level (≥0.3 mg/dL [≥26.5 μmol/L]) was noted in 242 participants (5.4%) and a decrease in GFR (≥29 mL/min/1.73 m2) was noted in 224 participants (5%; Table 1). Men with increased creatinine levels were significantly older, had decreased HDL levels, were more likely to be hypertensive, had greater rates of

Discussion

In this study of apparently healthy men at baseline, we evaluated analgesic use and change in kidney function during a 14-year period and found no evidence of a decline in kidney function, assessed by either a plasma creatinine level elevation of 0.3 mg/dL or greater (≥26.5 μmol/L) or a GFR reduction of 29 mL/min/1.73 m2 or greater, with increasing analgesic intake of any kind. Use of 2,500 analgesic pills or more during the 14-year study period (3 to 4 pills/wk) did not increase the risk for

Acknowledgements

The authors thank the participants in the PHS for their outstanding commitment and cooperation; the entire PHS staff for their expert and unfailing assistance; Vadim Bubes, PhD, for programming support; and Patrick J. Skerrett, MA, for assistance in editing the manuscript.

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    Supported in part by grants no. CA 34944 and CA 40360 from the National Cancer Institute; grants no. HL 26490 and HL 34595 from the National Heart, Lung, and Blood Institute, Bethesda, MD; and a grant from McNeil Consumer Products.

    1

    The sponsor of the study had no role in study design, data collection, data analysis, data interpretation, or the writing of the manuscript.

    2

    Dr. Glynn received consulting fees from AstraZeneca and grant support from Bristol-Meyers Squibb.

    3

    Dr. Walker is employed by Ingenix, Auburndale, MA. United Health Group owns both Ingenix and UnitedHealth Care. UnitedHealth Care, as an insurer, has a financial interest in cost-effective reduction of kidney disease risk. At various times, he has conducted research sponsored by most manufacturers of NSAIDs.

    4

    Dr.Hennekens received research grant support from Bayer and PharMed. He serves as a consultant, including Chair or Membership on Data and Safety Monitoring Boards, to AstraZeneca, Bayer, Bristol-Myers Squibb, Chattem, GlaxoSmith Kline, McNeil, Novartis, Pfizer, and Reliant. He is a co-inventor on patents concerning inflammatory markers and cardiovascular disease, which are held by Brigham and Women's Hospital.

    5

    Dr. Gaziano received research funds from BASF, McNeil, Roche, and Wyeth. During 2002 and 2003, he also served as a consultant to McNeil and Wyeth.

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