Can NSAIDS cause CKD?

1349 5
I recently saw a patient in clinic who was referred for a creatinine of 1.5, stable for a number of years. She had no other risk factors for CKD except a history of daily NSAID use for chronic back pain. Her exam and urinalysis were unremarkable. After seeing her, I decided to review the evidence for NSAIDs causing chronic renal damage—I wasn’t sure this was a diagnosis I could hang my hat on. In doing so, I found it worthwhile to review the mechanisms of NSAID-related kidney damage, acute and long term.

NSAIDs are a well-recognized cause of renal dysfunction. Their inhibition of COX-1 diminishes the production of prostaglandins that mediate renal vascular tone, natriuresis, and ADH responsiveness. Acute effects of NSAID intake, usually in high doses, include:

  • Decreased glomerular filtration (renal ischemia that often develops in the setting of compromised renal perfusion, e.g. volume depletion or CHF)
  • Salt and water retention (COX-1 mediated prostaglandins inhibit Na transport in the TAL and collecting duct; they also antagonize ADH function)
  • Hyperkalemia (by blunting prostaglandin-related renin release, which decreases aldosterone formation; also, without prostaglandins to diminish Na reabsorption the loop of Henle, less sodium arrives at the distal nephron, meaning less Na-K exchange takes place)
  • Interstitial nephritis
  • Nephrotic syndrome
  • Acute renal papillary necrosis (a severe sequela of renal ischemia)
However, most of these complications are readily reversed by discontinuing the offending NSAID. What about chronic renal dysfunction following long-term NSAID intake? In today’s medical environment, the evidence is weak. Prospective cohort studies in the Physicians’ Health Study (Rexrode et al, JAMA 2001) and the Nurses’ Health Study (Curhan et al, Arch Int Med 2004) failed to show an association between even high levels of cumulative lifetime NSAID intake and decrease in renal function.

While NSAID-induced chronic renal papillary necrosis (also called analgesic-abuse nephropathy) was a common occurrence several decades ago, it was largely due to use of phenacetin-containing analgesic compounds. Phenacetin has been off the market since 1983 in the United States, and has been banned in most countries*. Chronic papillary necrosis has been reported with other NSAIDS, but extremely rarely, and the incidence has not been determined.

So it seems I can’t hang my hat on my patient’s NSAID use as a cause of her CKD, although I am curious to see what happens to her creatinine after she stops taking them. If her renal function continues to decline, she may be headed for a biopsy.

*A web search for phenacetin yielded multiple internet retailers of phenacetin, most from mainland China. It looks like it is only sold in bulk (i.e. 25 kg drums)—an amount to make any nephrologist shudder.


  1. in2015 my daugters gfr was dropping and mine was 55 since 2013…. i decided to cut out my daily high dose of ibuprofen thati had taken for over 20 years,,, just hoping my grf would remain 55,, never dreaming it would get higher,,but surprise in 2016 my gfr was 70 and my creatinine level that had been 1 was now .8…. i also followed a very strict low salt diet.. i was 71-72 during this change…..last 2 years ave been stressful and having a lot of pain.. i went back to ibuprofen,,, in december my creatinine was 1.2 and my gfr dropped to 44… i think i was a little deydrated… but still,,, i am forever off buprofen,,, that is the only thing that could explain the increase as well as the later decrease… it took about a year to get the increase and aout 2 years for the decrease in gfr

  2. This happened to me! For 20+ years, I took NSAIDs daily. Mainly, ibuprofen and naproxen for menstrual pain and chronic headaches. I ended up with an 8mm clot in my abdominal aorta, and an atrophied kidney.

    NSAID use stopped at that time. Nine years later, living with one kidney and acquired thrombocythemia, I am on several meds for high BP and mild diabetes, as well as platlet reducers, statins, cholesterol reducers, etc.

    To doctors: Don't just advise your patients not to overuse NSAIDs, scream at them!

  3. Hello, I am a 50 year old female caucasion patient. I have used (possibly excessive) NSAIDS for many years (I am a distance runner, and have used them during/after marathons and training runs, plus, for general aches and pains, over a 20+ year period).

    Had a routine blood draw a few days ago with eGFR of 56, creatinine 1.04, cholesterol 237. My doctor poo-poohed it, I insisted on a urine test for protein, which came back positive (trace amounts). Now have an appointment with a nephrologist. Had I not obtained my own lab results and insisted on perseverence, I wouldn't even have known about the low eGFR. Until I have more testing done, I am avoiding NSAIDs. Period. That's just me and my two cents, a lay person. And I am scared. My family doctor knew nothing about CKD, I had to do all my own research.

  4. I think there are a lot of nephrologists who have faced the same patient scenario you mention. (Including me!) Perhaps those patients who do seem to have a decrease in GFR from chronic NSAID use have undetected underlying kidney disease? It would be interesting to follow the persons in the Nurses' or Health Professionals' studies who did have an elevated creatinine in the setting of high NSAID intake. Perhaps they share a characteristic that makes them susceptible to NSAID-related renal damage. In any case: I agree with your second point. Many of our patients have painful comorbid conditions, and denying them analgesics without evidence for harm is cruel.

  5. I used not to believe that there is such an entity. But over the past year I had about 3 cases where I could only blame the DAILY use of NSAIDs. I stopped it completely and sure enough GFR improved but very slowly. I mean it took 6 months to see Cr trending down to where it belongs. Without biopsies, there is not definitive answer. It walks like a duck and looks like a duck, guess what: it's a duck.

    My problem is when I see the common practice of nephrologists to BAN the use of NSAIDs completely as if it's a sin when GFR is in 40s and 50s. I think that is excessive.

Leave a Reply