Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used throughout the world to treat pain and inflammation. Only a small fraction of NSAID users get significant kidney damage, but this is still a large number of people.

There are two types: the non-specific NSAIDs include aspirin, ibuprofen and naproxen, all available over-the-counter. More options are available by prescription. The other type is known as COX-2 inhibitors, or coxibs. Currently, the only COX-2 inhibitor available in the United States is Celebrex. Two others, Vioxx and Bextra, were taken off the market after they caused an unacceptable increase in cardiovascular illness and death.

All NSAIDs work by blocking the action of cyclooxygenase (COX). This enzyme performs a key step in the synthesis of prostaglandins, which produce many effects in the body. Two of the effects are pain and inflammation for injured tissue. Other effects include protection of the stomach and homeostasis (regulation) of kidney function. The COX enzyme comes in two forms, COX-1 and COX-2. For a while, it was thought that COX-2 produces the pain and inflammation prostaglandins, while COX-1 produces the protective and regulatory prostaglandins. Thus, the COX-2 inhibitors were supposed to be a safer alternative to the older drugs.

However, both non-specific NSAIDs and COX-2 inhibitors present similar risks of kidney symptoms, including:
1. Salt and water retention,
2. Edema (excess tissue fluid),
3. High blood pressure, and
4. Elevated potassium levels in the blood.
The causes of these symptoms have been diagnosed as interstitial nephritis, nephrotic syndrome, renal papillary necrosis, and acute renal dysfunction.

Salt and water retention due to NSAIDs is of special concern to the 20 million Americans who currently take both NSAIDs and drugs for high blood pressure. NSAIDs may increase blood pressure by about 5 mmHg, and increase salt sensitivity.

Patients with diabetes, congestive heart failure, or age-related decline in kidney function are also at increased risk of kidney dysfunction from NSAIDs. There are many alternatives to NSAIDs for pain treatment, depending on the cause. These alternatives include physical therapy, chiropractic, acupuncture, massage, stretching, yoga, ice, heat, menthol creams, capsaicin creams, ergonomic furniture, and psychotherapy.

by Linda Fugate, Ph.D.

References:

Weir MR, “Renal effects of nonselective NSAIDs and coxibs”, Cleveland Clinic Journal of Medicine 2002; 69 Supplement 1: SI53-8

Coruzzi G, Venturi N, Spaggiari S, “Gastrointestinal safety of novel nonsteroidal antiinflammatory drugs: selective COX-2 inhibitors and beyond”, Acta Biomed 2007; 78:96-110.

“How Much Salt Is Too Much?”, https://www.empowher.com/news/herarticle/2009/08/31/how-much-salt-too-much