Proton Pump Inhibitors Linked to Kidney Injury

APRIL 26, 2015

Older patients taking proton pump inhibitors (PPIs) are more than twice as likely to be hospitalized with kidney failure.


PPIs are commonly prescribed for heartburn and acid reflux. In fact, 14.9 million patients received 157 million prescriptions for PPIs in 2012 alone.

Although the drugs are generally considered safe and well-tolerated, limited evidence suggests PPIs may cause acute interstitial nephritis, particularly among older patients. 


Acute interstitial nephritis is a form of renal injury that accounts for up to one-quarter of acute kidney injury cases. Although it is rarely life-threatening, acute interstitial nephritis may be associated with important consequences such as hospital admission, dialysis, corticosteroid therapy, and chronic kidney disease.


In a study published in CMAJ Open, researchers at the Institute for Clinical Evaluative Sciences and St. Michael’s Hospital looked at patients aged 66 years and older who were prescribed PPIs and compared their risk of acute kidney failure and acute interstitial nephritis.


A total of 581,184 individuals from Ontario Canada were identified over a 9-year span from 2002 to 2011. Individuals were categorized into 2 groups: those who began treatment with PPIs during the study period, and those who were not prescribed PPIs. 


Individuals were excluded from the study if they prior had PPI use within 1 year, diagnosed systemic illnesses associated with interstitial nephritis, end-stage renal disease, or were newly prescribed other medications associated with acute interstitial nephritis. 


The primary outcome of the study was hospital admission with acute kidney injury within 120 days of the patient’s first PPI prescription, while the secondary outcome was the risk of acute interstitial nephritis.


In the main analysis, a higher rate of hospital admission with acute kidney injury was observed among patients receiving a PPI than those not receiving a PPI (1269 vs. 518 cases; 13.49 vs. 5.46 per 1000 person-years; HR=2.52, 95% CI: 2.27-2.79). Similar results were found when looking at the effects of individual PPIs on acute kidney injury.


In the secondary analysis, there was a similar increase in the risk of acute interstitial nephritis (30 vs 10 cases; 0.32 vs. 0.11 per 1000 person-years; HR=3.00, 95% CI: 2.30-2.91).


Since acute kidney injury may not be attributed to PPI therapy, the authors speculated many patients would resume therapy after discharge. Of the 937 such patients in the study discharged from hospital, more than half (556; 59%) received another prescription for a PPI in the following 100 days. Of these patients, 42 (7.5%) were readmitted to hospital with acute kidney injury in the following 120 days. 


The authors acknowledged several limitations of the study, including only using administrative data, setting a broad definition of acute kidney injury, and the possibly of unmeasured confounding variables.


“Although our study should not deter clinicians from prescribing PPIs for patients with well-defined indications, our findings underscore the importance of ongoing efforts to curtail the indiscriminate use of these drugs,” the authors wrote.


Of the millions of individuals taking PPIs each year, more than half of such prescriptions may not be clinically indicated.

Timothy O'Shea, PharmD
Timothy O'Shea, PharmD
Timothy O'Shea, PharmD, is a Clinical Pharmacist working at a large health insurance plan on the east coast. Additionally he works per diem at a retail pharmacy chain. He graduated from MCPHS University - Boston in 2015 and subsequently completed a PGY-1 Managed Care Pharmacy Residency. His professional interests include pharmacy legislation and managed care pharmacy. He can be followed on Twitter at @toshea125.
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