Can over-the-counter pain medications cause kidney disease? How can patients with kidney disease treat their pain?

The fact that a number of painkillers are available freely over-the-counter (OTC) often gives a lot of people a false sense of security about the safety of these medications. A statement that I here from some of my patients is, "it was available without a prescription, so I thought it wasn't too strong". So very often, patients assume that if a medicine is not too potent, it probably does not have serious side effects either. Sadly, a medication's potency is not necessarily proportional to its side effect profile.


HOW DO PAIN MEDICATIONS DAMAGE THE KIDNEYS: EFFECTS ON KIDNEY FUNCTION

Pain medications can have different renal effects. These can range from reversible, short term reductions in kidney function due to a decrease in the blood supply to the kidneys (called Acute Renal Failure, or Acute Kidney Injury), to a more chronic disease where the kidneys shrink in size, develop a rough and bumpy surface, and demonstrate tissue breakdown called "papillary necrosis".
This latter entity is called Analgesic Nephropathy. Patients who have analgesic nephropathy from phenacetin are at a much higher risk of certain cancers of the urinary tract (Transitional Cell Carcinoma of the renal pelvis/ureter/bladder). Finally, certain medications can cause other changes in the kidney (Acute Interstitial Nephritis, Membranous Nephropathy, Minimal Change Disease) which can be accompanied by leakage of huge amounts of protein in to the urine (Nephrotic Syndrome).


Some painkillers interfere with production of a chemical called "prostaglandin". This chemical usually dilates the blood vessels  and is necessary for adequate blood supply to the kidneys. Hence use of these painkillers can not only cause Acute Renal Failure, it could also lead to an increase in your blood pressure.


A BIT OF HISTORY

On July 7th, 1946, the flamboyant aviator, Howard Hughes crash landed in Beverly Hills while performing a test flight for the USAF XF-11 reconnaissance aircraft. He survived the crash, but would live in chronic pain for the next 30 years, until his death in 1976. He lived through those three painful decades, all the while self medicating himself with a cocktail of pain medications. One of these pain medications was phenacetin, a precursor of acetaminophen. After his death, his autopsy showed atrophy of his kidneys and papillary necrosis. However, phenacetin's damaging effects on the kidney would not be well known until November 1983, when the FDA ordered all drugs containing phenacetin to be taken off the market (eg. a previous version of Saridon). Phenacetin, till that time had been a part of a number of OTC combination pain medications with aspirin, codeine, acetaminophen, barbiturates, etc. In fact, before 1983, up to 3 percent of all cases of kidney failure (ten percent in North Carolina!) in the US, and around 10-20 percent in Australia and Europe were attributed to combination analgesic pain medications containing phenacetin. This rate fell dramatically once such combination medications were taken off the market.


Image courtesy of Marin/ FreeDigitalPhotos.net




THE MEDICATIONS TO BE AWARE OF:

For the purpose of this discussion, I will divide OTC painkillers in to three categories: acetaminophen (trade name: Tylenol), aspirin, and other non-steroidal anti-inflammatory drugs (NSAIDS). Lets assume that current readers will not have access to the dreaded phenacetin that I mentioned above. Let me also state that pain killers aren't the only medications that cause kidney disease. However, it is their easy availability and widespread use that makes them a huge risk factor, and thus a risk factor where public education can go a long way in preventing bad outcomes.


1) Acetaminophen (Tylenol)
There is some, although not very strong evidence that acetaminophen use alone can be associated with analgesic nephropathy and consequent irreversible kidney disease, with some studies supporting this conclusion and others refuting it. What is more certain though is that this risk is probably not as great as being on a phenacetin-aspirin combo regimen. It is speculated that even though acetaminophen is a metabolite of phenacetin, it might not be as damaging to the kidney as its parent compound.

2) Aspirin
Most medical studies do not indicate aspirin use alone to be associated with kidney disease. However, it is well established that aspirin can potentiate the damaging effect of phenacetin or acetaminophen when taken in combination with those meds.

3) NSAIDS
Examples of NSAIDS include ibuprofen (Motrin, Advil), indomethacin, Aleve, etc. The short term derangement of kidney function (described above) from NSAIDS is well known. There is also some evidence to indicate that chronic kidney damage/disease can occur potentially occur from any NSAID (including the newer selective COX-2 inhibitors); however some NSAIDS might be better than others including low dose aspirin, ibuprofen, and sulindac.



WHAT PAIN MEDICATIONS ARE SAFE TO TAKE IN PATIENTS WITH KIDNEY DISEASE?

If you do not have any kidney disease, but are taking pain medications on a long term basis, it might be a good idea to touch base with your doctor to see where your kidney function stands, and keep an eye on it. However, if you already have kidney disease, or risk factors for kidney disease (diabetes, heart disease, high blood pressure) then pain management needs to be customized. Dose or frequency reduction (eg. dosing acetaminophen every six hours instead of four) are often warranted. A medication called tramadol may be considered since it not known to be toxic to the kidneys. Short acting NSAIDS might be better. This will need coordination between your doctor, nephrologist, and/or pain specialist.

Veeraish Chauhan, MD, FACP, FASN
Nephrology 
Bradenton, Sarasota, FL 

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