The People's Perspective on Medicine

Can PPI Heartburn Drugs Harm Kidneys Without Early Symptoms?

A new study suggest that long-term use of potent acid-suppressing drugs (PPIs) may increase the risk of chronic kidney disease without much warning.
People, healthcare and problem concept – unhappy woman suffering from stomach ache over gray background

Millions of people take prescription-strength acid-suppressing medications daily. Millions more take over-the-counter versions. A new study suggests that such PPI heartburn drugs may trigger serious kidney disease without a lot of advance warning. When kidneys fail, the situation can rapidly become  life threatening.

What Drugs Are Under Scrutiny:

PPIs, or proton pump inhibitors, are sold under names such as dexlansoprazole (Dexilant), esomeprazole (Nexium and Nexium 24HR), lansoprazole (Prevacid and Prevacid 24HR), omeprazole (Prilosec and Prilosec OTC), pantoprazole (Protonix) and rabeprazole (AcipHex). We have known for over a decade that this class of medicines was linked to what doctors call acute kidney injury (AKI). This condition can come on suddenly. Australian researchers alerted their colleagues in the journal Clinical Gastroenterology and Hepatology (May, 2006) that there was a problem:

“Proton pump inhibitors (PPIs) are a widely prescribed class of drugs, and their usage worldwide is increasing. Although well-tolerated, there have been case reports and a recent case series implicating these drugs in acute interstitial nephritis (AIN) and progression to acute renal failure (ARF).”

What Are the Symptoms of Acute Kidney Injury?

When kidneys are damaged because of hemorrhage, very low blood pressure, really bad diarrhea, heart failure, severe burns, major surgery or overuse of NSAID-type pain relievers, there are symptoms to watch out for. They may include:

Reduced urine flow
Edema (fluid retention; swelling of ankles, legs or even around the eyes)
Fatigue or exhaustion
Mental cloudiness or confusion
Difficulty breathing or shortness of breath
Digestive distress
In severe cases, people may go into coma.

Some or all of these symptoms can show up during an acute episode of kidney injury. Some people may experience damage to the kidneys without obvious symptoms, until the situation becomes quite grave.

Many people recover from acute kidney injury, especially if the underlying causative factor(s) is resolved promptly. Some patients may require dialysis or a kidney transplant. AKI can be deadly when the damage is severe.

Dear Reader: Please note the following:

There has been a dramatic increase in cases of acute kidney injury over the last two decades. The cost to society of AKI is over $10 billion annually.

We offer no editorial comment or associations to medication use. We do have a question for kidney experts. What accounts for this dramatic change?

The Shocking Results of the New Study:

The new research published in Kidney International (Feb. 22, 2017) is quite alarming. That’s because the investigators wanted to know whether chronic kidney disease (CKD) occurs after acute injury to the kidneys or if it can develop without any early warning signs of AKI. In other words, can CKD occur without passing Go and without collecting $200?, to use the tired old Monopoly metaphor.

The answer seems to be yes.

Here’s the dilemma for doctors and patients. If PPI heartburn drugs can trigger chronic kidney disease or irreversible kidney failure without early warning signs, we are quite alarmed.

What The Study Discovered:

The researchers evaluated 125,596 new users of PPI heartburn drugs. These patients were tracked over five years. What investigators found was worrisome. Please pardon the medical jargon, but we wanted you to read the findings in the authors’ own words:

“In this work, we show that among new users of acid suppression therapy, incident PPI users have an increased risk of chronic renal outcomes including incident CKD [chronic kidney disease], CKD progression, and ESRD [end stage renal disease] in the absence of intervening AKI [acute kidney injury]…”

…”The finding that PPI use is associated with adverse chronic renal outcomes independent of the occurrence of AKI suggests that monitoring for AKI or acute interstitial nephritis among PPI users is not sufficient to guard against the development of CKD and ESRD… ”

“Reliance on antecedent AKI as warning sign to guard against the risk of the development of CKD and progression to ESRD among PPI users is not sufficient as a sole risk mitigation strategy. Exercising vigilance in PPI use, even in the absence of AKI, and careful attention to kidney function in PPI users may be a reasonable approach.”

What these researchers are saying is that some long-term PPI users can end up with failing kidneys without a lot of advance warning. Doctors who rely on signs and symptoms of acute kidney injury may miss serious underlying kidney disease. That’s a very big deal.

A Double Whammy?

Have you ever heard of the law of unintended consequences? This means that when you mandate a change some of the results may not be what you anticipated or wanted. For example, in the 1920s America adopted Prohibition with the aim of preventing alcohol abuse and alcoholism. The consequences, however, were that people continued to drink even though it was illegal. Organized crime and rum runners took over the business of operating manufacturing, transporting and selling booze. Some of the bootleg gin doubtless harmed people because of contamination.

Many adverse drug events can be unintended consequences of well intentioned therapy. Nonsteroidal anti-inflammatory drugs such as diclofenac, ibuprofen, meloxicam or naproxen can cause severe damage to the digestive tract. Sometimes people end up with heartburn, serious stomachaches or even bleeding ulcers. That’s why health professionals often prescribe PPIs in an attempt to protect the stomach lining from harm.

But here’s the rub. NSAIDs can cause kidney injury. Now we know that PPIs can also cause kidney damage. As far as we can tell, no one has looked into the possibility that this combination (an NSAID plus a PPI) could be worse than either drug alone. You read that here first. We hope researchers begin investigating this potential problem. In the meantime, people who are on both kinds of medicine simultaneously should be especially cautious. If you are taking these drugs, even over the counter, let your doctor know and request kidney function tests!

What Can Patients Do?

First and foremost, be vigilant! In our opinion, anyone who relies on PPI heartburn drugs on a regular basis for long periods of time should be checked periodically for kidney function. There may be no early warning symptoms of kidney injury.

Next, follow the instructions on the label of over-the-counter PPI heartburn drugs like Nexium 24HR or Prilosec OTC. Do not assume that just because these are nonprescription medications they are super safe. The directions often say:

  • do not use for more than 14 days unless directed by your doctor
  • you may repeat a 14-day course every 4 months
  • do not take for more than 14 days or more often than every 4 months unless directed by a doctor

If your doctor hands you a prescription for a proton pump inhibitor, ask how long you should take it. The FDA has not approved PPI heartburn drugs for unlimited use. For example, the official prescribing information says that:

“NEXIUM is indicated for short-term treatment (4 to 8 weeks) of heartburn and other symptoms associated with GERD [gastroesophageal reflux disease] in adults and children 1 year or older.”

Other drugs in this class share similar FDA-sanctioned recommendations. Even for “erosive esophagitis,” which is serious irritation of the esophagus, the FDA does not suggest treatment beyond six months.

Where Is the FDA in all of this?

In our opinion, the Food and Drug Administration has been way too silent on the growing controversy around PPI heartburn drugs and kidney damage. If an herb or a dietary supplement could trigger kidney failure it would be on the FDA hit list. There would be headlines about the travesty and calls to ban such a dangerous product.

We do not think the FDA has done enough to warn health professionals or patients about problems with proton pump inhibitors. Want to learn more? Here is a link to an article titled “Why Are Americans Now Worried About New PPI Side Effects?

Stopping PPIs Suddenly Can Be Disastrous!

In our opinion, the FDA has also not adequately alerted people to problems of withdrawal associated with PPIs. When someone has taken these acid-suppressing drugs for several weeks and then stops, they may experience rebound hyperacidity. In other words, really bad heartburn.

If you would like to learn more about how to get off a PPI without experiencing unbearable withdrawal symptoms, here is a link to an article titled: “How Can You Get Off a PPI Without Withdrawal?”

Do not ever stop taking a prescribed medication without discussing the situation with your doctor. There are some conditions that may make taking a proton pump inhibitor for long periods of time absolutely necessary. If that is the case, be sure to let your prescriber know that you want your kidney function to be monitored closely.

Share your own story about PPI heartburn drugs below in the comment section.

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.” .
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Sadly, I have stage 3 kidney disease due to being prescribed Aciphex for 11 years. I suffered GERD, and because I couldn’t take Prilosec or Nexium, the Aciphex was the answer. It did control my extreme heartburn and reflux. Then I learned 11 years down the road that my kidneys were not healthy. Shame on doctors who don’t do research on this PPI danger.

I immediately stopped taking Aciphex and began taking Zantac to help with the stopping Aciphex. It worked well, and I had no problems. I take 150 mg before breakfast and 300 mg before my evening meal and no reflux in the middle of the night while I am sleeping.
I have been on Zantac now for 4 plus years and no reflux problems. If only I had been prescribed Zantac back when, my kidneys would still be ok.

This lesson has now caused me to be very proactive in my health care. I research any medication my doctor might want me to take and know exactly the side affects. Better safe than sorry.

Doctors and drug companies tell you have too much acid in your stomach, why you need PPI pills.
Its just opposite heart burn cause you don’t have enough acid in your stomach
Take Betsibe HCI tablets, Hydrochorlic Acid.
I started these tabs and work good lot better then pills.
Research Hydrochorlic Acid for hesrburn you be amazed.

My kidney function has been decreasing for about five years. I’ve been on Nexium for just as long. I’m also severely low in iron, another unintended consequence from decreasing acid, which is needed to break down iron.

I quit Nexium a week ago and do have what I’d consider hyperacidity. I suspect quitting Nexium will be the best thing I’ve done for my health in a long time. Shame on the FDA for burying their heads in the sand. It goes to show they cannot be trusted and these drugs should not be otc.

Sadly, after 14 years on Prilosec I have decided to go off it cold turkey. So far, no rebound acid to speak of but I use an H2 inhibitor in the AM and 1 in the PM just in case. For 14 years I have been symptom free and no evidence of kidney problems.

It is a wonderful drug for its intended purpose but I hear such negativity from many places about possible kidney damage risk that I fear continuing to use it. I have had bad heartburn since I was a child and really suffered with it. My age: 82 and counting. I hope the H2 will do the job for me in my remaining years.

If you have kidney damage due to a PPI and stop the ppi can you reverse the damage? Any information you can add on this topic would be greatly appreciated.

The WCTU/prohibition analogy does not work in this case. WCTU was an astroturf movement funded by one cynical man, J.D Rockefeller, taking advantage of low information religious people to force another man, Henry Ford, to abandon his biofuel/biodiesel proposals which depended on ethanol instead of ground oil.

Gastroesophageal reflux is worse in areas of hard water and/or with elemental calcium additives to diet or pills. The calcium and the PPI’s both are associated with magnesium depletion which this study might show is associated with renal injury. Local norms for magnesium in labs vary widely depending on whether doctors are still pushing calcium supplements and the amount of calcium in the water – many “normals” are really magnesium depleted. Most pharma studies take place in “soft” water cities which skews the safety data originally considered by the FDA.

I was put on PPI tablets to counteract the side effects of other medication I was on. Personally I found they caused me to retain Fluid and then I found I could eat very few foods without getting a sick stomach as I hadn’t enough acid in my stomach to digest my food properly, My GP did monitor my Kidney function every six months but I really did not like this drug and weaned myself off it which was very difficult but I eventually managed it and now I’m back enjoying my food again I have no real issues with my stomach which makes me wonder why I was ever put on a PPI to start with. It worries me that an over the counter version is now available as you do need your Kidney function tested while on these drugs. I think the danger to your kidneys should be on the box.

I was prescribed omeprazole during chemotherapy which lasted 5 months. I am now finished with chemotherapy and am in the process off weaning off the omeprazole. I was never advised on how to stop taking the drug and just quit taking it, this was the worst thing I could have done. My symptoms blasted full force. I then purchased the pamphlet from Peoples Pharmacy and followed the directions. I am 1 week away from being off this drug completely, by following the directions I had zero adverse effects.
Thank you for making all this good information available to us.

What dosage of the PPI was used for the studies? I read someplace that many of the studies used higher doses of the PPI than the over the counter recommended dose. I.E. Prilosec OTC is 20 mg a day, while the studies used 40 or 60 mg or higher. How long were the participants on the PPI?

Also, were there other possible causes for the problems?

Lastly, what was the real increased risk and did it go away after stopping the PPI?

Thanks for any information.

Gary, the doses were not specified, but these were prescriptions. So they fell into the range of prescription doses. The entire follow-up was five years, but the researchers did not specify the minimum amount of time for which a prescribed PPI was taken. They carefully considered other causes of kidney damage to do statistical controls for the study.

The real increased risk is low, but the number of people taking PPIs is high. That translates into a lot of people at risk. Acute kidney injury may be reversed after stopping the PPI; chronic kidney disease is by definition not reversible.

Hello , To read this Article is shocking . My Husband was on pantoprazole
for about 6 years , Then 2015 he got Bladder Cancer and last year he
passed away . Very shocking , Thank you

The author doesn’t state how many of the 125.5 thousand new users developed kidney disease. I would be curious to read the study to see if there were any underlying conditions. I understand the need for caution. As a sufferer of GERD for in excess of 15years, I have tried many different modalities to come off a PPI only to have to start all over again.

Thank you for being such a reliable source of info. From the consumer’s POV.

I forwarded this issue to two of my retired pharmacist friends.

Thanks for this. Could not understand why my ankles were swelling so much. I was started on this type of Rx after an endoscopic procedure. Why I never knew. Also have documented 3rd stage renal failure. Considering the brain fog and increased shortness of breath I stopped this drug. I let my Dr. know.

I would like to get off my PPI but every doctor I have discussed it with says no because I have BE and I need to be concerned about esophageal cancer. I don’t know what to do.

My doctor put me on Omeprazole 20 mg daily in 2005. He said that the drug was safe and not to worry about it even though I would probably need it for the rest of my life. Omeprazole worked very well–I was virtually symptom free as long as I took it daily.

In 2013 I decided to stop taking it because of the many health problems associated with it. My doctor was unhelpful, saying only that I shouldn’t worry about it since the associated health problems were “just anecdotal.” I didn’t agree, based on my own reading of medical studies and the numerous reports from other patients experiencing problems.

So, I began a slow taper of the Omeprazole. I reduced the dosage by one tablet per week. For instance, on week one I skipped my Sunday dose, but took my dose on every other day. On week 2 I skipped Sunday and Wednesday, and so on. The whole taper worked very well, and by week 7 I was medication and symptom free. I continue to take an antacid or Zantac for occasional heartburn, but that happens just once per month or so.

Thank you. I switched to famitodine a few years ago to get off PPIs.

In our zeal to encourage more carbohydrate intake we also saw the unintended consequence of increased heartburn and indigestion. Most health care professionals do not think to look at the amount of carbohydrate an individual is ingesting and if recommendations on diet could help alleviate the problems.
When we went from the Basic 4 food groups with 4 servings a day to the Pyramid with 9 or more servings a day of breads/starches/grains, not only did weight greatly increase, but also heartburn and indigestion.

Some people find relief eating their carbohydrates earlier in the day and less with the evening meal and before bed.

My husband has an issue with heartburn and, as I age, I occasionally have problems. However, when my long-term diet omits packaged breads, cookies, cereals, pasta, etc. (even ‘healthy’ ones) and includes limited grains, and focuses on eating vegetables and fruits as close as they come “from the ground’ (i.e. raw foods in salads or lightly/simply cooked) with a small amount of protein, I have absolutely no heartburn – even if I eat a relatively big meal late at night before bed.

How ironic that I need the PPI (so says my doc) because I have scleroderma of the esophagus, but will probably die from one of the many nasty side effects of the PPI rather than my diagnosis!

By the way, I had taken Prilesec for a few cays and it made my body ache.

My second doctor [first doctor’s nurse called me and yelled at me about prescription insurance, saying I must be on Prilesec prescription for the rest of my life, and it is expensive !!!] suggested that I eat at least 3 hours before bed, don’t bend over immediately after eating, small meals and so forth…I’m doing just fine ! no drugs, occasional Tums.

I listen to your radio programs on Saturday mornings, wish they were replayed later in the day. My friends don’t connect that early !! I believe less medicine is much healthier for all of us.. thanks, Janelle

I have been consuming one tablespoon of apple vinegar with my morning juice. Has eliminated acid reflux.

I developed an irregular urine flow and went to the doctor where they gave me a test and said I had nothing wrong. Now I read that this is one sign of kidney failure along with fatigue, which I have and a few other things. Not too happy about this. Will have to find another doctor and go through it all over again.

Is pepsid safe?

Do you have any information on Pantoprazole 40MG tablets prescribed to be taken at night?
Been listening to your program for a very long time.
Thank you.

Is famotidine included on this list? Thanks-

Famotidine, like cimetidine, is not a PPI.

In my case, my gastroenterologist and his staff think the risk of kidney failure is low. I have tried getting off of the generic form of Aciphex using your Guide to Digestive Disorders which I purchased a few years ago. It didn’t work; the acid reflux continued, mainly because I have an extremely slow digestive system, which I think contributes to my symptoms.

The Aciphex gives me extreme diarrhea, which disrupts my life. I do have a hiatal hernia and am overweight also, which I’m sure does not help! All I know is I want to get off this PPI!

Naprosyn can also cause kidney damage if used long-term. Kidney function studies should be done for people who use it regularly. I am a victim.

I have been taking a generic version of Prilosec (purchased at a warehouse store) for a few years without incident. I too, read the 14 day restrictions and came up with a successful method of treatment without any issues.

I have adapted the dosage, and most importantly, have discussed this with my doctor who has given his OK. Twice yearly blood tests monitor that all is well with kidney function.

This is what I do:
— I purchased a pill cutter and cut each oval pill in half. I cut the entire pack of 48 pills at one time, then store in a labelled Rx bottle.
— I take ONE of these cut pills….EVERY OTHER DAY.

That’s it! If for some reason, I overlook taking them for 3 or more days (which occasionally happens) mild heartburn returns….and then I just take one of the cut pills, and get back on the regular schedule.

The dosage is just enough to control the heartburn, and the (original 48 count) pill pack last for months!

As someone who has taken OTC PPI for years every day this is of great concern. I did read an article similar to this a year or two ago but did not stop the ppi’s. I had severe heartburn that led to my throat being irritated and certain foods would get caught going down. Before I started taking PPI’s I had 2 cases of me going to the hospital for treatment ( inserted tube and pushed down the food and one case of a procedure to stretch my throat by a “specialist”.

No one suggested PPIs until a third episode occurred and the doctor telling me after the procedure ” its a mess down there ” and suggested I start PPIs. Since I started taking them every day there have been almost no episodes and none requiring me going to the hospital. That’s probably 8 years or more. I’ve contemplated using tums or other antacids and stopping the PPI’s… Any thoughts ?

Very good and timely information. Thanks for keeping us informed. Although I have never used any PPI medication, the information is still useful.

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