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More than 5% of patients with moderate-to-severe chronic kidney disease regularly take nonsteroidal anti-inflammatory drugs (NSAIDs), despite the National Kidney Foundation's recommendation that these agents be avoided in patients with chronic kidney disease, a large cross-sectional study showed.

This adds up to more than 870,000 U.S. patients whose kidneys are at risk for further NSAID-induced injury, according to Laura Plantinga, ScM, of the University of California San Francisco, and colleagues.

In addition, among those with moderate-to-severe disease who were current NSAID users, 65.7% had been taking the drugs for a year or more, the researchers reported in the September Annals of Family Medicine.

Most patients with chronic kidney disease (CKD), which becomes symptomatic only with the development of end-stage renal disease, are unaware of their condition. They are also unaware that NSAIDs are potentially harmful to them because of the effects of decreases in prostaglandin synthesis.

NSAIDs also can have unwanted interactions with common medications such as angiotensin receptor blockers and angiotensin-converting enzyme inhibitors.

To assess the extent of use of these drugs, Plantinga and colleagues analyzed data from the National Health and Nutrition Examination Survey from the years 1999 to 2004.

A total of 12,065 adults responded to a questionnaire about analgesic use. They also had samples available for serum creatinine and urine albumin and creatinine.

Mild CKD was defined as an estimated glomerular filtration rate of 60 mL/min per 1.73 m² and higher, and albuminuria of 30 mg/g or more.

The disease was classified as moderate-to-severe when the glomerular filtration rate was between 59 and 15 mL/min.

The questionnaire asked about a number of NSAIDS, including naproxen, indomethacin, and diclofenac, but excluded aspirin and acetaminophen, which are less nephrotoxic than other NSAIDs.

In addition, aspirin is recommended for the prevention of cardiovascular disease even among patients with CKD, and acetaminophen is recommended for their pain.

A total of 79.6% of participants had normal kidney function, while mild CKD was present in 9.4% and severe disease in 11%.

Patients with CKD were more likely to be women, older, and black, and to have lower levels of income and education.

In the overall study population, 3.7% were considered current NSAID users, in that they had used the drugs daily or almost every day for the past month.

Most of the NSAIDs were over-the-counter formulations, but 19.4% of current users also had a prescription for one of the drugs.

Patients who were aware they had kidney disease were just as likely to use NSAIDs as those who were unaware (5.7% versus 5%, P=0.80), the researchers noted.

Among patients with mild CKD who were current NSAID users, 19.4% had prescriptions for an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, as did 19.1% of those with moderate-to-severe disease.

In addition, 17.8% of NSAID users with moderate-to-severe disease also had prescriptions for loop diuretics.

"The nephrotoxicity of and potential interactions with these drugs may need to be more clearly communicated to primary care clinicians, other prescribers of medications for pain management, and the community," the researchers observed.

But they also noted that there was a two- to five-fold higher rate of NSAID use among patients with arthritis in their cohort. Arthritis pain may be more troubling to patients, and more limiting in quality of life, than CKD, they added.

They concluded that "clinicians are advised to consider the risks and benefits on a case-by-case basis, with determination and consideration of their patients' [CKD] status and over-the-counter NSAID use."

Limitations of the study include its cross-sectional design, which precludes inference of causality.

Moreover, patients may have inaccurately reported their duration and frequency of analgesic use, and there may have been misclassification of early-stage kidney disease.

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