Nonsteroidal Anti-inflammatory Drugs Can Injure Your Kidneys

When I awaken and first get out of bed, I feel my seventy-one years of age.  Decades of weight bearing exercise including running, jogging and walking, in addition to basketball and tennis on hard surfaces, has contributed to wear and tear arthritic discomfort.  I think all the time about popping naproxen, ibuprofen or some other medicine for pain but the risk of an adverse event results in me sucking it up and working through it. 

These wonderful pain medications work by inhibiting prostaglandins involved in the inflammatory response. One of those prostaglandins also keeps the coronary arteries open. The NSAIDS can inhibit the mucous covering of the stomach leading to stomach inflammation and bleeding. 

As a physician caring for senior adults these incredible pain killers can injure the kidneys. By the time we reach 70 years of age most of us have naturally lost 70% of our functioning kidney cells. We do very well with the remaining 25% if we do not stress the kidney asking it to call on reserves it no longer possesses.

A study on the kidney effects of these drugs was published in the Clinical Journal of the American Society of Nephrology in April 2021 by physicians working in Hong Kong. They performed a retrospective analysis of kidney function in almost 2 million Chinese individuals in Hong Kong – all over 18 and with normal kidney function. The study looked at those individuals with a prescription for a NSAID for a minimum of 28 days and found a marked decrease in their Glomerular Filtration Rate (GFR) and a 94% increased risk of a decline of GFR of 30% or greater.

The study looked at ibuprofen, celecoxib, diclofenac, indomethacin, naproxen, piroxicam, sulindac and mefenamic acid. The average patient was 55 years old and 53% were women.  Their results showed that ibuprofen was the least likely to lower GFR indicating kidney injury but even it conferred a risk of 12% on GFR declining to less than 60%.

The findings of this study reinforce what we already know. A steady diet of NSAIDs will injure your kidneys.  An occasional dosage is probably still safe if you take it with food in your stomach and remain well hydrated.

We live in a society where physical exercise and activity are encouraged for health.  Long-term activity will lead to morning stiffness and aches and pains. Traditional opioid pain medications are addictive and clearly not the answer. NSAIDs were hoped to be safer but apparently not so on a long-term steady basis.

Fish Oils in Osteoarthritis – Low Dose vs. High Dose

Using the common sense approach that if a little bit is good then more is better in the treatment of “rheumatism” Catherine Hill, M.D., of the University of Adelaide in Australia and colleagues looked at the effect of taking low dose fish oil supplements versus high dose fish oil supplements. When one looks at the adult population of Australia, one third of them take fish oil supplements and had within a month of this study. The typical dose is one ml of fish oil per day. Experts say the dose for anti-inflammatory effect for arthritis is considerably higher at 2.7 gram or 10 ml per day. Dr Hill’s theory was that high dose fish oil for symptomatic and structural outcomes in people with knee osteoarthritis was better.

She enrolled 202 symptomatic patients in a double blind study. High dose group patients received 4.5 g EPA/HPA per day. The low dose group were given a blended of fish oil containing 0.45 g EPA /DHA per day in combination with Sunola oil. Both supplements were flavored with citrus oil.

All patients received a baseline MRI of the knee at inception of the study and at two years. The patients mean age was 61 years and body mass index was 29kg/meter squared. Both groups showed x-ray evidence of arthritis in the knee at inception and both groups were allowed to take non-steroidal anti-inflammatory medications and acetaminophen for arthritic pain during the course of the study.

At two years there was no difference in the MRI findings or cartilage volume loss between the high dose and low dose groups. Each group took similar amounts of NSAIDs and acetaminophen for pain on a regular basis. The high dose had no benefit over the low dose.

The researchers concluded that there was no benefit in their study to high dose versus low dose fish oil supplementation for arthritis. They reasoned that since patients in the study were permitted to take additional fish oils on their own during the study this may have altered the findings. The researchers additionally had little control over how much fish the participants ate.

In reviewing the data it seems to indicate that fish oil played a minor role in slowing down arthritis in the knee joint. Low dosage had as good of an effect as high dosage but the studies lack of a true control group who did not take fish oil at all made the conclusions hard to accept.

I will suggest to my patients that they continue to eat two fleshy fish meals per week to get their fish oils for arthritis and cardiovascular protection, rather than purchasing and taking low dose or high dose fish oil supplements.

Are Non-Steroidal Anti-inflammatory Drugs Safe?

In recent months patients and physicians have been challenged to find safe medications to relieve pain. Nonsteroidal anti-inflammatory drugs such as ibuprofen, naproxen and others were once the mainstay of simple pain relief. We knew that they could irritate the lining of your stomach and possibly cause gastrointestinal bleeding so we suggested that you take them with food in your stomach. We knew they could injure your kidneys so we reduced the dosage and frequency to individuals with kidney issues. When reports came out that these effective pain medications were contributing to acute heart attacks through coronary artery spasm, we grew leery of prescribing them. In recent years after a pharmaceutical industry push to use narcotics for pain relief we are confronted with addiction and all its negative connotations to deal with if we use opioids to relieve pain. What then is available to prescribe for pain?

The SCOT (Standard Care vs Celoxicab Study), championed by, Thomas M MacDonald, MD, of the University of Scotland Dundee helped provide an answer. The study was discussed at the meetings of the European Society of Cardiology this week with results that show that older patients with no heart disease history had no increased risk of heart attack or stroke while using NSAID drugs for extended treatment. They followed 7297 patients 60 years of age or older for three years who were prescribed celecoxib (Celebrex) or another nonsteroidal drug. The endpoint of the study was a heart attack, a stroke or the discovery of new cardiovascular disease. The number of new heart attacks or strokes was actually far lower than predicted proving that these drugs do not cause heart attacks or strokes in cardiovascular disease free individuals. The study did not look at these drugs effect on individuals with documented heart or cardiovascular disease.

In recent months the Food and Drug Administration has insisted that manufacturers of NSAID’s specifically inform and warn consumers of the increased risk of a heart attack within weeks of starting the drug and increasing with time. This study will now allow us to relieve the pain of the young athletic individual with musculoskeletal pain without fearing we are setting them up for a cardiovascular calamity.

Cold and Flu Season Coming

As we head into fall and winter we see an increase in the number of viral respiratory illnesses in the community. Most of these are simple self-limited infections that healthy individuals can weather after a period of a few days to a week of being uncomfortable from runny noses, sinus congestion, sore throats, coughs, aches and pains and sometimes fever. There are studies out of Scandinavia conducted in extreme cold temperature environments that show that taking an extra gram of Vitamin C per day reduces the number of these infections and the severity and duration in elite athletes and Special Forces military troops. Starting extra vitamin C once you develop symptoms does little to shorten the duration or lessen the intensity of the illness. Vigorous hand washing and avoidance of sick individuals helps as well. Flu shots prevent viral influenza and should be taken by all adults unless they have a specific contraindication to influenza. A cold is not the flu or influenza. Whooping cough or pertussis vaccination with TDap should be taken by all middle aged and senior adults as well to update their pertussis immunity. We often see pictures of individuals wearing cloth surgical masks in crowded areas to prevent being exposed to a viral illness. Those cloth surgical masks keep the wearers secretions and “germs” contained from others but do nothing to prevent infectious agents others are emitting from getting through the pores of the mask and infecting them. If you wish to wear a mask that is effective in keeping infectious agents out then you need to be using an N95 respirator mask.

Once you exhibit viral upper respiratory tract symptoms care is supportive. If you are a running a fever of 101 degrees or higher taking Tylenol or a NSAID will bring the fever down. Staying hydrated with warm fluids, soups and broths helps. Resting when tired helps. Most adults do not “catch” strep throat unless they are exposed to young children usually ages 2-7 that have strep throat. Sore throats feel better with warm fluids, throat lozenges and rest.

You need to see your doctor if you have a chronic illness such as asthma , COPD, heart failure or an immunosuppressive disease which impairs your immune system and you develop a viral illness with a fever of 100.8 or higher. If your fever is 101 or greater for more than 24 hours it is the time to contact your doctor. Breathing difficulty is a red flag for the need to contact your physician immediately.

Most of these viral illnesses will make you feel miserable but will resolve on their own with rest, common sense and plenty of fluids.

Study Reveals No Deterioration of Kidney Function …

NSAIDSAs we age and try and keep moving we notice the severe aches and pains from wear and tear and osteoarthritis that we feel at the start of a day. To relieve those feelings we often reach for the over the counter bottle of Advil ( ibuprofen) or Aleve ( naproxen sodium) knowing full well that the medication will help the aches and pains but may irritate our stomach or contribute to the downfall of our kidneys.

The problem and decision making in prescribing NSAIDs is even more critical in patients with Rheumatoid Arthritis. A recent scientific publication in the Annals of Rheumatic Disease 2015:74: 718-723 authored by B Moeller MD of the Unselspital-University Hospital, Bern, Switzerland looked at this question. They “found reassuring data regarding preserved renal function despite long-term NSAID use in Rheumatoid Arthritis (RA) patients.” Kidney function was followed on 4101 RA patients between 1996 and 2007. 2739 patients used NSAID while 136 2 patients did not.

They assessed and followed kidney function by the accepted methods of calculating the Glomerular Filtration Rate ( GFR). Their results revealed that there was no decline in kidney function in patients who had less than stage 4 Chronic Kidney Disease at the start of the study. They went on to recommend that if a patient’s eGFR or glomerular filtration rate was less than 30 ml per minute they should not take NSAIDs to treat their aches and pains from RA because of the high risk of these medications exacerbating their already compromised kidney function.

The study included medicine from two different classes of NSAIDs, both the “coxib” and “rofecoxib” class. With this data it is safe to say that individuals with arthritic aches and pains can take NSAIDs without fear of kidney deterioration as long as they do not already have severe chronic kidney disease.

Non Steroidal Anti-Inflammatory Drug (NSAID) Use and Heart Attacks

Most of us weekend warriors are used to reaching for the ibuprofen , naproxen or aspirin for relief from aches and pains after some strenuous gardening, yard work or recreational exercise. It helps alleviate the pains and allows one to go on with their life and perform the normal activities of daily living.

For many individuals with advanced osteoarthritis or the more severe types of immunological arthritis such as rheumatoid arthritis or psoriatic arthritis, these medicines are liberating and allow patients to live a normal life. For many years the major concern with these medications was their effect on the stomach causing irritation, inflammation and gastrointestinal bleeding. Then experts issued warnings about long term use and liver and kidney damage.  These side effects were listed on the product insert and were not unexpected.

What was unexpected was the association of NSAID’s and acute heart attacks. Drugs like Vioxx and Bextra, which were extraordinarily effective at relieving aches and pains, were pulled from the market after being determined to dramatically increase the number of acute myocardial infarctions users suffered. The NSAID’s reduced joint pain and inflammation by inhibiting chemicals called prostaglandins. Unfortunately the same inhibition of prostaglandins that produced less inflammation and joint pain also inhibited prostaglandins that kept our coronary arteries from going into spasm and cutting off the circulation to our heart muscle. For several years now pharmaceutical manufacturers have been looking for the perfect formula that inhibits joint inflammation without increasing heart attack risks.

A recent study from Denmark indicated that their search has not yet been successful. Denmark maintains detailed records of patient hospital admissions and medication usage as well as a central national death registry.  Using these data bases, the records of 84,000 patients admitted to a hospital for treatment of a myocardial infarction from 1997-2006 were reviewed and linked to pharmacy records. Researchers found that 43.3% of the MI patients received NSAID’s post MI and there were 35,257 deaths or repeat heart attacks.

“Overall NSAID treatment was related to a significantly increased risk of death at the beginning of the treatment and the risk persisted throughout the treatment. Patients taking Celebrex had an increased risk of death when the treatment lasted two weeks to a month.  All NSAID’s increased the risk of death or recurrent MI by 45% after a week.  Naproxen increased the risk of death or recurrent MI by 76% after a week. For treatment lasting 30-90 days the increased risk was 15%.  Ibuprofen had the lowest initial risk, just 4% increase for treatments lasting seven days or less.

In practical terms, we must limit NSAID use to the absolute minimum in patients with established cardiovascular disease.  Based on this article, ibuprofen seems to be the best choice for short term use in patients with known cardiovascular disease. Patients with cardiovascular disease and known previous MI should be talking to their doctor before they reach for the over-the-counter bottle of a NSAID.