Children taking the common painkillers known as nonsteroidal anti-inflammatory drugs may be at risk for acute kidney damage, particularly when the kids are dehydrated, a new study finds.
Nonsteroidal anti-inflammatory drugs (commonly called NSAIDs), such as ibuprofen (brand names Advil and Motrin), naproxen (Aleve) and ketorolac (Toradol) are used to relieve pain and fever.
“The one thing we did see that seemed to be connected to kidney damage was dehydration,” said lead researcher Dr. Jason Misurac, a nephrologist at Indiana University School of Medicine in Indianapolis.
For the study, which was published in the Jan. 25 online edition of the Journal of Pediatrics, Misurac’s team looked at the medical records of children admitted to Riley Hospital for Children in Indianapolis from 1999 through mid-2010. Over that time, they identified more than 1,000 cases of children being treated for kidney damage.
In nearly 3 percent of the cases, the damage was related to NSAIDs, the study found. Most kids were teens, but four were under 5 years old. All of them had been given NSAIDs before being hospitalized. Since many other cases involved several causes of kidney damage, it is possible some of those also were related to NSAIDs, the researchers said.
Most children who developed kidney damage had been given the recommended dose and had not been taking NSAIDs for more than a week.
In adults, taking NSAIDs regularly for several years has been tied to kidney problems, according to the U.S. National Institute of Diabetes and Digestive and Kidney Diseases. Cases involving children have previously been reported but only rarely.
Misurac noted that most of the children in the study hadn’t been drinking well and also were vomiting and had diarrhea, all of which can lead to dehydration. When someone is dehydrated the kidneys have a way of protecting themselves, which NSAIDs block, resulting in the damage, Misurac explained.
“Certainly in the way NSAIDs affect the kidneys, it’s reasonable to think that dehydration plus an NSAID has more of an effect than just an NSAID by itself,” he said.
Often the signs of kidney problems aren’t apparent, Misurac said. One sign is a decrease in urine; another is stomach pain. “But most kids who have episodes of acute kidney injury have nonspecific symptoms and there’s no one way to tell,” he said.
“If kids are dehydrated and not drinking well, then parents should think twice about using NSAIDs,” Misurac said. Tylenol (acetaminophen), which acts differently than NSAIDs, might be a better choice for children, he said.
For many of the children in the study, the kidney damage was reversed, Misurac said. The damage, however, was permanent for seven patients and they will probably need ongoing monitoring and treatment for declining kidney function, he said.
All the children under age 5 had to undergo dialysis and were more likely to be treated in an intensive-care unit, the researchers said. They also stayed in the hospital longer.
Although the study showed an association between taking NSAIDs and kidney problems in children, it didn’t establish a cause-and-effect relationship.
One expert agreed that NSAIDs can damage the kidneys.
“This is well known. Unfortunately, it is better known among doctors; the public is not as educated regarding this problem,” said Dr. Felix Ramirez-Seijas, director of pediatric nephrology at Miami Children’s Hospital.
Ramirez-Seijas said NSAIDs are “overused and abused, both by doctors and patients.”
For children, most fevers should not be treated; fever is how the body fights infection, he said. “There is a fear of fever that leads to overtreatment,” Ramirez-Seijas said.
In addition, children who take NSAIDs for aches after vigorous exercise also are at risk, because they may be dehydrated, Ramirez-Seijas said.
His advice to parents is to be sure children are well hydrated if they are going take NSAIDs. In addition, he believes that even these over-the-counter drugs should only be used with the advice of a doctor.
“Most people see taking a couple of Advil like taking a sip of water, but it’s not,” Ramirez-Seijas said.
Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
What are NSAIDs and how do they work?
Prostaglandins are a family of chemicals that are produced by the cells of the body and have several important functions. They promote inflammation that is necessary for healing, but also results in pain, and fever; support the blood clotting function of platelets; and protect the lining of the stomach from the damaging effects of acid.
Prostaglandins are produced within the body’s cells by the enzyme cyclooxygenase (COX). There are two COX enzymes, COX-1 and COX-2. Both enzymes produce prostaglandins that promote inflammation, pain, and fever. However, only COX-1 produces prostaglandins that support platelets and protect the stomach. Nonsteroidal anti-inflammatory drugs (NSAIDs) block the COX enzymes and reduce prostaglandins throughout the body. As a consequence, ongoing inflammation, pain, and fever are reduced. Since the prostaglandins that protect the stomach and support platelets and blood clotting also are reduced, NSAIDs can cause ulcers in the stomach and promote bleeding.
What NSAIDs are approved in the United States?
The following list is an example of NSAIDs available:
- celecoxib (Celebrex)
- diclofenac (Cambia, Cataflam, Voltaren-XR, Zipsor, Zorvolex)
- diflunisal (Dolobid – discontinued brand)
- etodolac (Lodine – discontinued brand)
- ibuprofen (Motrin, Advil)
- indomethacin (Indocin)
- ketoprofen (Active-Ketoprofen [Orudis – discontinued brand])
- ketorolac (Toradol – discontinued brand)
- nabumetone (Relafen – discontinued brand)
- naproxen (Aleve, Anaprox, Naprelan, Naprosyn)
- oxaprozin (Daypro)
- piroxicam (Feldene)
- salsalate (Disalsate [Amigesic – discontinued brand])
- sulindac (Clinoril – discontinued brand)
- tolmetin (Tolectin – discontinued brand)
What are the side effects of NSAIDs?
NSAIDs are associated with several side effects. The frequency of side effects varies among NSAIDs.
Common side effects are
- decreased appetite,
- headache, and
Other important side effects are:
- kidney failure (primarily with chronic use),
- liver failure,
- ulcers, and
- prolonged bleeding after injury or surgery.
NSAIDs can cause fluid retention which can lead to edema, which is most commonly manifested by swelling of the ankles.
WARNING: Some individuals are allergic to NSAIDs and may develop shortness of breath when an NSAID is taken. People with asthma are at a higher risk for experiencing serious allergic reaction to NSAIDs. Individuals with a serious allergy to one NSAID are likely to experience a similar reaction to a different NSAID.
Use of aspirin in children and teenagers with chickenpox or influenza has been associated with the development of Reye’s syndrome, a serious and sometimes fatal liver disease. Therefore, aspirin and non-aspirin salicylates (for example, salsalate [Amigesic]) should not be used in children and teenagers with suspected or confirmed chickenpox or influenza.
NSAIDs increase the risk of potentially fatal, stomach and intestinal adverse reactions (for example, bleeding, ulcers, and perforation of the stomach or intestines). These events can occur at any time during treatment and without warning symptoms. Elderly patients are at greater risk for these adverse events. NSAIDs (except low dose aspirin) may increase the risk of potentially fatal heart attacks, stroke, and related conditions. This risk may increase with duration of use and in patients who have underlying risk factors for heart and blood vessel disease. Therefore, NSAIDs should not be used for the treatment of pain resulting from coronary artery bypass graft (CABG) surgery.
For what conditions are NSAIDs used?
NSAIDs are used primarily to treat inflammation, mild to moderate pain, and fever.
Specific uses include the treatment of:
- ankylosing spondylitis,
- sports injuries, and
- menstrual cramps.
- Ketorolac (Toradol) is only used for short-term treatment of moderately severe acute pain that otherwise would be treated with narcotics.
Aspirin (also an NSAID) is used to inhibit the clotting of blood and prevent strokes and heart attacks in individuals at high risk for strokes and heart attacks.
NSAIDs also are included in many cold and allergy preparations.
Celecoxib (Celebrex) is used for treating familial adenomatous polyposis (FAP) to prevent the formation and growth of colon polyps.
With which drugs do NSAIDs interact?
NSAIDs reduce blood flow to the kidneys and therefore reduce the action of diuretics (“water pills”) and decrease the elimination of lithium (Eskalith, Lithobid) and methotrexate (Rheumatrex, Trexall). As a result, the blood levels of these drugs may increase as may their side effects.
NSAIDs also decrease the ability of the blood to clot and therefore increase bleeding. When used with other drugs that also increase bleeding (for example, warfarin [Coumadin]), there is an increased likelihood of serious bleeding or complications of bleeding. Therefore, individuals who are taking drugs that reduce the ability of blood to clot should avoid prolonged use of NSAIDs.
NSAIDs also may increase blood pressure in patients with hypertension (high blood pressure) and therefore antagonize the action of drugs that are used to treat hypertension.
NSAIDs increase the negative effect of cyclosporine on kidney function.
Persons who have more than three alcoholic beverages per day may be at increased risk of developing stomach ulcers when taking NSAIDs.