NSAID Use in Chronic Kidney Disease Sparks Debate

Kate Johnson

September 14, 2011

September 14, 2011 — The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is just as common among patients with chronic kidney disease (CKD) as it is among the general public, despite concerns about the nephrotoxicity of these drugs, according to a study published in the September/October issue of the Annals of Family Medicine.

"Our findings suggest there may be large numbers of individuals with CKD, many of whom unaware of their disease, who may be at risk for further kidney injury through use of NSAIDs," write Laura Plantinga, ScM, from the University of California, San Francisco, and other members of the Centers for Disease Control and Prevention CKD Surveillance Team.

"CKD screening in those who use NSAIDs daily, and effective communication of the risks of NSAID use among those with CKD may be warranted to prevent further kidney damage and progression of disease," the investigators add.

The study used data from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004 to examine the use of over-the-counter and prescription NSAIDs in relation to CKD.

Better Risk Communication Needed

The authors suggested that the nephrotoxicity of and potential interactions with NSAIDs may need to be more clearly communicated to primary care physicians and other prescribers.

"Primary care physicians, who are likely to manage both early-stage CKD and indications for NSAID use, should be aware of NSAID (both prescribed and over-the-counter) use, assess the risk of NSAID use in each patient, and, most importantly, engage each patient in informed decision making about the risks and benefits of NSAID use," they recommend.

The study included a total of 12,065 adult survey participants (mean age, 51 years) who answered questions about both demographics and medication use and provided samples for the measurement of serum creatinine and urine albumin and creatinine.

CKD status was defined by using estimated glomerular rate (eGFR) and albumin-to-creatinine ratio (ACR) as follows:

  • No CKD: eGFR ≤ 60 mL/ min per 1.73 m2, and ACR ≤ 30 mg/g

  • Mild CKD (stages 1 and 2): eGFR ≥ 60 mL/min per 1.73 m2, and ACR ≥ 30 mg/g

  • Moderate to severe CKD (stages 3 and 4): eGFR 15 to 59 mL/min per 1.73 m2

In total, 80% of the study participants were classified as having no CKD (mean age, 47 years), 9% as having mild CKD (mean age, 57.5 years), and 11% as having moderate to severe CKD (mean age, 73 years).

Awareness of CKD Very Low

Awareness of having CKD, defined as a yes or no answer to "Have you ever been told by a doctor or other health professional that you have weak or failing kidneys?" was very low among study participants, with 95.6% of those with mild disease and 90% of those with moderate to severe disease being unaware of their illness.

NSAID use was defined by self-reported use of ibuprofen, naproxen, sulindac, piroxicam, indomethacin, tolmetin, or diclofenac (with brand names and combination formulas identi?ed) daily or nearly every day for the past 30 days.

Long-term use was de?ned as use for 1 year or longer.

Self-reported cardiovascular disease, hypertension, obesity, cancer, arthritis, and use of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers were also recorded.

Overall, current use of NSAIDs was "not uncommon" (3.5%) in the general US population and "low but not rare" among those with both mild and moderate to severe CKD (4.3% and 5.7%, respectively), report the authors.

"At a population level, this percentage reflects up to 870,000 persons in the United States with advanced CKD who are using NSAIDs," they write.

"Among those with CKD, current NSAID use was similar among those [who] were aware and those who were unaware of their CKD status (5.7% vs 5.0%, P = .80)," they note.

In addition, long-term use of NSAIDs was reported by two thirds of users (66%) and did not differ between those with and those without CKD.

Among patients with CKD who reported NSAID use, 10% of those with moderate to severe disease and 11% of those with mild disease reported having an NSAID prescription, "possibly reflecting the lack of both clinician awareness of CKD status and possible adverse effects of NSAIDs in patients with CKD who have additional competing indications for NSAID use," the authors suggest.

Although arthritis was reported by 28% of the overall cohort, it was more common in patients with CKD (35% of those with mild CKD and 44% of those with moderate to severe CKD) than in those without CKD (23%).

Patients with CKD who used NSAIDs also reported other prescription drug use. Specifically, 16% of NSAID users with stage 3 CKD and 20% with stage 4 CKD also had prescriptions for angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and loop diuretics.

Contradictory Evidence

 While describing the "general consensus" that NSAIDs should be avoided in CKD, the authors also acknowledge that there is contradictory evidence for this risk, a factor that might contribute to the continuing use of NSAIDs in this population. Additionally, they suggest that in considering patients’ overall quality of life, the benefits of NSAID use may be considered to outweigh the risks.

Asked to comment on the findings, Jeffrey Berns, MD, professor of medicine and pediatrics at the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, said they did not ring any alarm bells.

"The number of people taking significant amounts of NSAIDs was actually not that high," he told Medscape Medical News. "Among those who had some impairment of kidney function…a small percentage of them were taking NSAIDs on a long-term basis, and of that relatively small number of patients some may have had an impact on their kidney function because of the NSAID use."

But it’s still an open question as to how much NSAID use contributes to kidney problems, he added.

"We don’t have great evidence to indicate the regular, low-dose NSAID use is deleterious in terms of kidney disease progression or even short-term GFR in the vast majority of patients."

A more contemporary cohort of patients might look quite different, he added, given that current awareness of CKD is much higher than it was at the time of the survey.

"There were a lot of patients who were unaware that they had CKD. I’m not sure that is the case any longer. I think [today] their doctors would be more likely to be aware of CKD, and more attentive to their patient’s NSAID use."

"Patients don’t always report over-the-counter medication use, so one of the messages out of this paper is to emphasize to physicians that they ought to be asking about this."

The study was supported under a cooperative agreement from the Centers for Disease Control and Prevention through the Association of American Medical Colleges. One of the study authors (Dr. Robinson) received grants in the last 3 years from Abbott Laboratories, Amgen, Genzyme Corporation, and Kyowa Hakko Kirin. Another study author (Dr. Powe) is partially supported by the National Institute of Diabetes and Digestive and Kidney Diseases. No other study authors have disclosed relevant financial relationships. Dr. Berns is editor-in-chief of Medscape Nephrology and has served as an advisor or consultant for Amgen Inc.

Ann Fam Med. 2011;9:423-430. Abstract

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