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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.

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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