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PPIs linked to kidney function decline even in patients with no kidney problems

The use of proton pump inhibitors may cause serious kidney problems that can go undetected for some time, according to research that recently appeared in Kidney International.

“The onset of acute kidney problems is not a reliable warning sign for clinicians to detect a decline in kidney function among patients taking proton pump inhibitors,” Ziyad Al-Aly, MD, Clinical Epidemiology Center, VA St. Louis Health Care System, said in a press release. “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.”

Al-Aly and colleagues studied data from 125,596 patients who were new users of proton pump inhibitors (PPI), as well as another 18,436 patients who were new users of histamine H2 receptor antagonists.

They found that over 5 years of follow-up in survival models where cohort participants were censored at the time of acute kidney injury occurrence, incident users of PPI had increased risk for estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m² (HR = 1.19; 95% CI,1.15-1.24), incident chronic kidney disease (HR = 1.26; 95% CI, 1.2-1.33), eGFR decline of greater than 30% (HR = 1.22; 95% CI-1.16-1.28), and eGFR decline of more than 50% or end-stage renal disease (HR = 1.3; CI=1.15-1.48) when compared with the incident users of histamine H2 receptor antagonists. The researchers also stated that results were consistent in models which excluded participants with acute kidney injury before chronic renal outcomes, acute kidney injury during time in cohort, and acute kidney injury before cohort entry.

The proportion of PPI effect mediated by acute kidney injury was 44.7% for incident eGFR less than 60 mL/min/1.73 m², 45.47% for incident chronic kidney disease, 46% for eGFR decline greater than 30%, and 46.72% for end-stage renal disease or greater than 50% decline in eGFR.

Al-Aly and colleagues stated that their results were consistent using various acute kidney injury definitions, such as inpatient ICD-9 codes, Kidney Disease Improving Global Outcomes and the National Health Services England.

They also noted a lack of research on how PPI affect the kidney.

“We conducted a systematic PubMed search using a comprehensive list of search terms to identify animal studies of PPI-induced acute or chronic renal injury. The search results yielded zero published animal studies,” researchers wrote. “The conspicuous absence of published literature evaluating possible mechanisms of PPI-related renal injury suggests significant knowledge gap, and highlights the pressing need for experimental work to further enhance our understanding of the effect of PPI on the kidney.

Until that research can provide answers, Al-Aly suggested that physicians carefully consider recommending PPI to their patients.

“Doctors must pay careful attention to kidney function in their patients who use PPI even when there are no signs of problems,” he said in the release. “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.”

Al-Aly’s and colleagues’ research is the latest in a series of studies that have shown possible consequences tied to PPI use. These include increased ischemic stroke risk, asthma in children whose mother used the inhibitors while pregnant, and increased risk for Clostridium difficile infection in children. – by Janel Miller

Disclosure: The researchers report no relevant financial disclosures.