2017-11-08 21:32:36 UTC

More Data on PPI Use and Kidney Disease

Nov. 8, 2017

A new meta-analysis on PPIs and kidney disease makes mainstream headlines. Here is what you, and your patients, need to know.

By J. Sumner Bell III, MD, FACP, AGAF, AGA's Patient Initiative Advisor, and Daniel Freedberg, MD, MS.
Another recent study has made headlines in the medical and lay press reporting an association between proton pump inhibitors (PPIs) and chronic kidney disease (CKD). Patients read these reports and are, justifiably, concerned. It is important that gastroenterologists understand these studies and can address any patient concerns appropriately.
What were the findings of this recent study?
The most recent study related to PPIs and CKD was a meta-analysis by Wijarnpreecha et al. presented at the American Society of Nephrology annual meeting and published in Digestive Diseases and Sciences. Meta-analyses pool the results of previously published studies to gain more confidence in estimates of effect (i.e., narrower confidence limits). Meta-analyses generally do not contain previously unpublished data and authors of meta-analyses rarely have access to original data. In this meta-anlaysis, the association between exposure to PPIs and risk for CKD or end-stage renal disease (ESRD) was examined across four large, retrospective studies. They found that any use of PPIs was associated with a 33 percent relative increase in risk for CKD/ESRD whereas no such risk was seen with H2RAs.
Does this mean that PPIs cause CKD/ESRD?
Meta-analyses share the limitations of their component studies. This is an association, not proof of a causal relationship. Patients who use PPIs differ at baseline than those who do not. For example, patients who use PPIs are more likely to have diabetes or hypertension than patients who do not use PPIs, and are more likely to use additional nephrotoxic medications. Large retrospective studies are unable to completely adjust for these baseline differences. These differences, rather than PPIs themselves, may explain the observed association.
Is there other evidence available related to PPIs and CKD?
Since the 1990s PPIs have been linked to cases of acute interstitial nephritis (AIN), an immune-mediated tubular renal injury that can be caused by many drugs. AIN is a rare cause of acute kidney injury and an even rarer cause of chronic kidney disease. AIN does not explain the PPI-CKD association; most CKD in the United States is linked to diabetes and hypertension. There is currently no proven mechanism connecting PPIs to CKD.
Have these recent studies changed the AGA’s recommendations regarding use of PPIs for gastroesophageal reflux disease (GERD) or other conditions?
Gastroenterologists should continue to prescribe PPIs when the benefits of PPIs exceed the risks. In all patients, the need for PPIs should be periodically reassessed and gastroenterologists should be familiar with PPI tapering strategies.
What advice is there for talking to patients with CKD who are receiving PPIs or who need treatment for reflux esophagitis or ulcers?
Talking to Your Patients
  1. Inform patients that, while this study does raise some concern about long-term PPI use and the potential contributions to kidney disease, the study does not show that PPI use causes kidney disease. No decisions should be made in haste as a reaction to this study. A brief explanation of the meta-analysis may also be helpful. 
  2. Reassure patients that the benefits of using PPIs often outweigh the possible risks. Let them know that you prescribed a PPI for a clear-cut indication, in the lowest possible dose, and for an appropriate period of time (lowest dose, shortest time). This advice echoes that offered by AGA and ABIM in the Choosing Wisely campaign.
  3. Consider various options for how your patient would like to move forward. Some patients may wish to consider trying an H2 antagonist instead of a PPI.
  4. Recommend that patients also consider lifestyle modifications that may reduce or eliminate the need for PPIs for long term use, as was concluded in the study “Lifestyle Intervention in Gastroesophageal Reflux Disease.”
  5. Keep conversation channels open with patients. Tell them that many patients require long-term use of PPIs as a highly effective therapy for many conditions. They shouldn’t stop medication without first talking with you about the risks and benefits. The need for PPIs should be periodically reassessed. Be sure to stay up-to-date on proper PPI tapering strategies.

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