Mills: Chronic Kidney Disease

Medical Associates of Northern New Mexico

Chronic kidney disease affects nearly 11 percent of Americans. Most causes of kidney injury are considered to be preventable; three-quarters of chronic kidney disease can be explained by diabetes and hypertension (high blood pressure) alone.

Perhaps a more insidious cause is from non-steroidal anti-inflammatory drugs (NSAIDs).

Marketed under the generic names ibuprofen and naproxen, NSAIDs are perhaps better known by their brand names Advil, Motrin and Aleve.  These readily available over-the-counter drugs exist in the majority of our medicine cabinets, and few of us think twice about taking a couple for that occasional headache or muscle ache.

It is common for a patient’s health care provider to be unaware of the frequency in which these medications are used by their patients.  In my experience, these medications make up a disproportionate number of kidney disease cases in Los Alamos (up to a third).

Kidney function can easily be measured with routine blood work.  A test for serum creatinine concentration is obtained to estimate kidney function.  

Serum creatinine is measured in milligrams per deciliter and can have a wide variability in interpretation. Using ones age, gender, race, and creatinine, an estimated glomerular filtration rate (eGFR) is obtained. Most people have an eGFR of 90-120 (ml/min/1.73m2) in early adulthood, but will naturally decline with age.  Normal renal function is defined as 60 or above in an average, healthy adult.  

eGFR represents the amount of aqueous serum from our blood that is passed through the filters of the kidney each day.  An important determinate of eGFR is kidney blood flow which is roughly three times the eGFR.  Thus, an average 18 year old male has approximately 500 liters of blood that will pass through the kidney each day (every drop of blood goes through the kidneys 100 times per day), roughly a quarter of all blood pumped by the heart.  

One hundred eighty liters are filtered, but more than 99 percent of that is reabsorbed during subsequent processing within the kidney. The resulting filtration (and reabsorption) of ones total blood volume 36 times a day provides more than adequate removal of water soluble waste products and toxins.

NSAIDs cause a significant dose dependent reduction in kidney blood flow.  This reduction occurs due to the drug-induced constriction of small arteries at the filters.   This can be so profound that NSAIDs alone have served for “medical nephrectomy,” or the removal of a kidney, in extreme cases.  Interestingly, this is not the most common means by which NSAID induced kidney injury occurs.  

Rather, this is because NSAIDs are the single most common cause for allergic interstitial nephritis (AIN), or inflammation within the kidney architecture.  Allergic white blood cells lead to inflammation, decreased kidney function, and eventually scarring.  

AIN is also responsible for kidney disease related to over-the-counter drugs, omeprazole (Prilosec), pantoprazole (Protonix) and esomeprazole (Nexium).  Fortunately, this condition can sometimes recover, but once suspected, the patient should refrain from NSAIDs indefinitely.  
Reduction in kidney blood flow by NSAIDs is significant nonetheless, and frequent harm can come when used during coexisting physiologic stressors.  

A frequent example is when a patient with vomiting and diarrhea who is volume depleted (i.e. dehydrated) takes an NSAID to lower a fever.  

Reduced blood volume from dehydration prevents normal blood delivery to the kidney and then is exacerbated by constriction of blood vessels from the NSAID.  The injured kidneys then cease to filter as certain cells within the kidney die due to lack of oxygen.  

Sometimes, the kidneys can recover. High blood pressure is associated with changes in renal blood flow, whereas diabetes frequently predisposes individuals to volume depletion.  Altitude also has an effect on reducing kidney blood flow, although this effect varies amongst individuals and with acclimatization to altitude.  

This brings us to an important question as to when or even if it is safe to take NSAIDs.  While the biases of some physicians may be that NSAIDs should never have been released over-the-counter (also a major cause of peptic ulcer disease and increases risk for stroke and heart attack), the fact remains that they are readily available and will remain to be so.

I feel that they should always be avoided in patients with acute dehydration, before or during vigorous exercise, and with alcohol.  Avoid NSAID use when exercising for periods of two hours or more. Although used successfully to reduce muscle soreness after training, it is far safer to train appropriately and gradually to avoid sudden severe soreness from overdoing it.  

Remember, altitude also has an effect on kidney blood flow.  There is significant increase risk for kidney damage when NSAIDs are used regularly with diuretics, blood pressure medications, or in diabetics.  I never advise daily use beyond a couple of weeks, but may be suggested by your primary care provider for chronic arthritic pain.  Just make sure your provider knows you are taking them, and they are checking your kidney function regularly.  Finally, any patient with known chronic kidney disease should avoid NSAID use altogether.

There are other options for over-the-counter pain relief.  Lidocaine skin patches, analgesic balms and heat/cold therapies can be effective for temporary relief. Acetaminophen may also serve as an alternative to NSAIDs, but also have their own risks, primarily related to the liver (never take with alcohol).  I recommend that patients discuss any and all over-the-counter drugs, vitamins, and natural or herbal supplements with their primary care provider.  

Beware that most supplements have not been evaluated for safety in kidney disease, and my general advice is to completely avoid them.