St. Louis—In patients using proton pump inhibitors (PPIs), chronic kidney issues often occur without the warning of an acute presentation, a new study cautions.

Because the damage occurs silently, according to the study published recently in the journal Kidney International, prescribers might not realize the need to discontinue the drugs, marketed under brand names such as Prevacid, Prilosec, Nexium, and Protonix, as well as available OTC.  

In fact, when the popular heartburn medications are used for prolonged periods, serious kidney damage can occur even in patients who show no signs of kidney problems, researchers at Washington University School of Medicine in St. Louis and the Veterans Affairs (VA) St. Louis Health Care System point out.

The new study of 125,000 VA patients suggests that more than half of those who develop chronic kidney damage on PPIs never presented with acute kidney problems beforehand. Because of that, the researchers urge more vigilance in monitoring the use of these medications.

“Our results indicate kidney problems can develop silently and gradually over time, eroding kidney function and leading to long-term kidney damage or even renal failure,” explained senior author Ziyad Al-Aly, MD, an assistant professor of medicine at Washington University School of Medicine. “Patients should be cautioned to tell their doctors if they’re taking PPIs and only use the drugs when necessary.”

For the study, researchers analyzed data from the Department of Veterans Affairs databases on 125,596 new users of PPIs and 18,436 new users of H2 blockers. Over 5 years of follow up, results indicate that more than 80% of PPI users did not develop acute kidney problems, which are usually reversible issues that create symptoms such as fatigue and swelling in the legs and ankles.

Compared with incident users of H2 blockers, incident users of PPIs had an increased risk of an estimated glomerular filtration rate (eGFR) under 60 ml/min/1.73m2 (hazard ratio 1.19), incident chronic kidney disease (CKD; HR 1.26), eGFR decline over 30% (HR 1.22), and end-stage renal disease (ESRD) or eGFR decline over 50% (HR 1.30).

The proportion of the PPI effect mediated by acute kidney injury (AKI) was 44.7%, 45.47%, 46.00%, and 46.72% for incident eGFR under 60 ml/min/1.73m2, incident CKD, eGFR decline over 30%, and ESRD or eGFR decline over 50%, respectively, according to the study, which adds, “Thus, PPI use is associated with increased risk of chronic renal outcomes in the absence of intervening AKI. Hence, reliance on antecedent AKI as warning sign to guard against the risk of CKD among PPI users is not sufficient as a sole mitigation strategy.

“Doctors must pay careful attention to kidney function in their patients who use PPIs, even when there are no signs of problems,” warned Al-Aly, who is also the VA’s associate chief of staff for research and education and co-director of the VA’s Clinical Epidemiology Center. “In general, we always advise clinicians to evaluate whether PPI use is medically necessary in the first place because the drugs carry significant risks, including a deterioration of kidney function.”

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