Nonsteroidal Anti-Infl ammatory Drug Use Among Persons With Chronic Kidney Disease in the United States 1,2 Laura Plantinga, ScM ABSTRACT 1 Vanessa Grubbs, MD PURPOSE Because avoidance of nonsteroidal anti-infl ammatory drugs (NSAIDs) is Urmimala Sarkar, MD1,2 recommended for most individuals with chronic kidney disease (CKD), we sought to characterize patterns of NSAID use among persons with CKD in the United States. Chi-yuan Hsu, MD1 METHODS A total of 12,065 adult (aged 20 years or older) participants in the 3 Elizabeth Hedgeman, MS cross-sectional National Health and Nutrition Examination Survey (1999-2004) Bruce Robinson, MD4 responded to a questionnaire regarding their use of over-the-counter and pre- 3 scription NSAIDs. NSAIDs (excluding aspirin and acetaminophen) were defi ned by Rajiv Saran, MD self-report. CKD was categorized as no CKD, mild CKD (stages 1 and 2; urinary Linda Geiss, MS5 albumin-creatinine ratio of ≥30 mg/g) and moderate to severe CKD (stages 3 and 4; estimated glomerular fi ltration rate of 15-59 mL/min/1.73 m2). Adjusted MPH5 Nilka Ríos Burrows, prevalence was calculated using multivariable logistic regression with appropriate Mark Eberhardt, PhD6 population-based weighting. 1,2 Neil Powe, MD RESULTS Current use (nearly every day for 30 days or longer) of any NSAID was For the CDC CKD Surveillance reported by 2.5%, 2.5%, and 5.0% of the US population with no, mild, and Team moderate to severe CKD, respectively; nearly all of the NSAIDs used were avail- able over-the-counter. Among those with moderate to severe CKD who were 1 Department of Medicine, University of currently using NSAIDs, 10.2% had a current NSAID prescription and 66.1% had California, San Francisco, California used NSAIDs for 1 year or longer. Among those with CKD, disease awareness 2Center for Vulnerable Populations, San was not associated with reduced current NSAID use: (3.8% vs 3.9%, aware vs Francisco General Hospital, San Francisco, unaware; P = .979). California CONCLUSIONS Physicians and other health care clinicians should be aware of use 3 Department of Medicine, University of of NSAIDs among those with CKD in the United States and evaluate NSAID use in Michigan, Ann Arbor, Michigan their CKD patients. 4Arbor Research Collaborative for Health, Ann Arbor, Michigan Ann Fam Med 2011;9:423-430. doi:10.1370/afm.1302. 5Division of Diabetes Translation, Cen- ters for Disease Control and Prevention, Atlanta, Georgia INTRODUCTION 6 National Center for Health Statistics, oth over-the-counter and prescription nonsteroidal anti-infl amma- Hyattsville, Maryland tory drugs (NSAIDs) are widely used in the United States.1 General medicine textbooks2-4 and nephrology subspecialty consensus guide- B 5 Confl icts of interest: B. Robinson received grants in lines (National Kidney Foundation) recommend avoidance of NSAIDs the last 3 years from Abbott Laboratories, Amgen, (except aspirin and acetaminophen) for most patients with chronic kidney Genzyme Corporation, and Kyowa Hakko Kirin; disease (CKD). Persons with CKD, however, are likely unaware of their all other authors report none. disease6 and may also be unaware that NSAIDs should be avoided. Addi- tionally, those with CKD are likely to be older and have multiple comor- CORRESPONDING AUTHOR bid conditions or symptoms that lead to increased use of NSAIDs.7 Laura Plantinga, ScM NSAIDs have been associated both with acute kidney injury in the Department of Epidemiology general population8 and with disease progression in those with CKD.9 Rollins School of Public Health For those with CKD, the further decrease in volume of renal blood fl ow Claudia Nance Rollins Building, 3rd Floor 1518 Clifton Rd NE resulting from decreased prostaglandin synthesis can lead to acute kidney 10 Atlanta, GA 30322 injury, sodium retention, edema, hypertension, and hyperkalemia. Acute [email protected] interstitial nephritis can cause kidney damage and reduced renal func- ANNALS OF FAMILY MEDICINE ✦ WWW.ANNFAMMED.ORG ✦ VOL. 9, NO. 5 ✦ SEPTEMBER/OCTOBER 2011 423 NSAID USE AND CHRONIC KIDNEY DISEASE tion in a small percentage of NSAID users.11 Habitual pants were asked to provide bottles of all prescription NSAID abuse can lead to analgesic nephropathy, a medications taken within the past month for recording condition that is often irreversible upon drug discon- by interviewers. Self-reported information on demo- tinuation.12 Additionally, NSAIDs interact unfavorably graphics (age, sex, and race/ethnicity), socioeconomic with some commonly prescribed medications, includ- status and health care access (education and income), ing loop diuretics, angiotensin-converting enzyme and diagnosed diseases and conditions was also inhibitors, and angiotensin receptor blockers, leading obtained during the interview. to reduced effectiveness, along with increased risk of Height, weight, and blood pressure were measured, renal impairment.13,14 Although epidemiologic studies and samples were collected during the examination. have linked NSAID use to progressive CKD,15 the risks Serum creatinine was measured by the modifi ed kinetic of NSAIDs in patients with CKD, while supported by method of Jaffe and corrected for different analyzers consensus and theoretical effect, remain less clearly as specifi ed in NHANES documentation.17,18 Urine established by evidence. albumin and creatinine were measured using solid- Despite the potential adverse renal effects of phase fl uorescence immunoassay and the modifi ed Jaffe NSAIDs, little is known about the patterns of NSAID kinetic method, respectively. use among those with CKD in community settings. Here we estimate the prevalence and describe pat- Defi nitions terns of self-reported NSAID use among adults by CKD CKD status using data from the community-based Patients’ CKD status was defi ned by single measure- National Health and Nutrition Examination Survey ments of kidney function (estimated glomerular fi ltra- (NHANES). tion rate [eGFR]) and albuminuria (albumin:creatinine ratio [ACR]), as follows: no CKD, eGFR ≥60 mL/ min/1.73 m2, and ACR ≤30 mg/g; stages 1 and 2 (mild METHODS CKD), eGFR ≥60 mL/min/1.73 m2, and ACR ≥30 Study Design mg/g; and stages 3 and 4 (moderate to severe CKD), We conducted a cross-sectional study of participants from NHANES, which consists of standardized Figure 1. Flowchart of cumulative study in-home interviews and physical examinations and participant exclusions. specimen collections at mobile examination centers of representative samples of noninstitutionalized US 16 14,213 All NHANES 1999-2004 civilian residents. A complex, multistage, probability participants ≥20 years old sampling design was used, with oversampling of cer- who underwent home tain subpopulations to increase reliability of estimates. interview and examination Response rates for participants completing both the interview and examination were 76% (1999-2000), 80% (2001-2002), and 76% (2003-2004), for a total of 14,213 Responding to 14,213 participants. analgesic questionnaire There were 12,065 NHANES 1999-2004 partici- pants (n = 3,753, 4,297, and 4,015 for 1999-2000, 2001- 2,125 Excluded 2002, and 2003-2004, respectively) who were aged 20 years or older, responded to the analgesic question- naire, and had available serum creatinine and urine 12,088 Available serum creatinine and urine albumin/creatinine data albumin and creatinine measurements; exclusions were pregnancy and estimated glomerular fi ltration rate 2 (eGFR) of less than 15 mL/min/1.73 m (Figure 1). All 23 Excluded participants gave written informed consent. The pro- tocol was approved by the National Center for Health 2 Statistics Research Ethics Review Board. 12,065 eGFR ≥15 mL/min/1.73 m Measurements During the interview, participants reported on current 12,065 Not pregnant and past use of specifi c over-the-counter and prescrip- tion analgesic pain relievers via a computer-assisted eGFR = estimated glomerular fi ltration rate; NHANES = National Health and personal interviewing system. Additionally, partici- Nutrition Examination Survey. ANNALS OF FAMILY MEDICINE ✦ WWW.ANNFAMMED.ORG ✦ VOL. 9, NO. 5 ✦ SEPTEMBER/OCTOBER 2011 424 NSAID USE AND CHRONIC KIDNEY DISEASE Figure 2. Questionnaire items and study defi nitions for reported over-the-counter and prescription NSAID use, National Health and Nutrition Examination Survey, 1999-2004. Questionnaire item: Have you ever taken any of these prescription or over-the-counter pain relievers nearly every day for a month or longer? Aspirin—also buffered aspirin products such Clinoril (sulindac) as Anacin, Bayer, Bufferin, Midol, Ascripton, Excedrin Ecotrin, Pabrin, and Alka Seltzer Feldene (piroxicam) Tylenol—including sinus products such as Anacin-3, Dristan AF, and Comtrex Indocin (indomethacin) Ibuprofen—also Advil, Nuprin, Motrin IB Relafen (nabumetone) (including cold and sinus products contain- Tolectin (tolmetin sodium) ing ibuprofen) Vanquish Aleve, Naprosyn (naproxen) Voltarin, Arthrotec (diclofenac) Celebrex (celecoxib) 2003-2004 only Vioxx (rofecoxib) 2003-2004 only No Yes No current use No ever chronic use Questionnaire item: Questionnaire item: No ever long-term use Do you For Ever currently use or take NSAID how many years did you chronic daily or nearly every day? take NSAID nearly every day? use No Yes <1 year ≥1 year No current use Current use No ever long- Ever long- term use term use NSAID = nonsteroidal anti-infl ammatory drug. eGFR 15-59 mL/min/1.73 m2. eGFR was calculated ity and recommended use for pain (acetaminophen) or according to the modifi ed Modifi cation of Diet in for the prevention of comorbid cardiovascular disease Renal Disease (MDRD) Study equation for calibrated (aspirin) in the setting of known CKD.20 creatinine was eGFR = 175 × [(calibrated serum creati- nine in mg/dL)-1.154] × age-0.203 × (0.742 if female) × Covariates (1.210 if African-American).19 Comorbid diseases were defi ned by self-reported diag- nosis. Self-reported cardiovascular disease was defi ned NSAID Use by diagnosed coronary artery disease, angina, myo- Current use of NSAIDs was defi ned by self-reported cardial infarction, stroke, or congestive heart failure.