Are PPIs Associated With Kidney and End Stage Renal Disease?

An association exists between proton pump inhibitors (PPIs) and risk of developing chronic kidney disease (CKD), kidney disease progression, and end-stage renal disease (ESRD), according to a new study.

“This is very important from an epidemiologic point of view and also from a clinical perspective,” said study author Ziyad Al-Aly, MD, of the Clinical Epidemiology Center, VA Saint Louis Health Care System. “We also show that risk increases with increased duration of exposure. The constellation of findings suggests a strong and intimate link between PPI use and untoward kidney outcomes.”
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The researchers used Department of Veterans Affairs national databases to build a primary cohort of new users of PPI (n=20,270) and new users of histamine H₂ receptor antagonists (H₂ blockers; n=173,321) and followed these patients over 5 years to ascertain renal outcomes.

In Cox survival models adjusted for demographic variables, estimated glomerular filtration rate (eGFR), clinical comorbid conditions, and other health characteristics, the PPI group, compared with the H₂ blockers group, had an increased risk of incident eGFR <60 mL/min per 1.73 m² and of incident CKD (hazard ratio [HR]=1.22, 95% confidence interval [CI]=1.18-1.26 and HR=1.28, 95% CI=1.23-1.34, respectively). Patients treated with PPI also had a significantly elevated risk of doubling of serum creatinine level (HR=1.53, 95% CI=1.42-1.65), of eGFR decline >30% (HR=1.32, 95% CI=1.28-1.37), and of ESRD (HR=1.96, 95% CI=1.21-3.18).

Furthermore, the researchers detected a graded association between duration of PPI exposure and risk of renal outcomes among those exposed to PPI for 31-90, 91-180, 181-360, and 361-720 days compared with those exposed for ≤30 days. Examination of risk of renal outcomes in 1:1 propensity score-matched cohorts of patients taking H₂ blockers vs patients taking PPI and patients taking PPI vs controls yielded consistent results.

“We suggest PPIs should only be used when medically indicated and duration of use be limited to the minimum that is medically necessary,” Al-Aly said. “We would also add, that while we think pharmacovigilance about safety of medications is important, our findings should not deter from use of PPIs when medically necessary.”

He said he thinks this study establishes a framework on how researchers can leverage the availability of “Big Data” and advanced analytics to better understand long-term outcomes of widely used medications.

“This domain interests us greatly,” Al-Aly said. “We certainly hope that our results will not only facilitate further discussion on PPI exposure and risk of renal outcomes but more broadly informs the discussion on how we can leverage the power of Big Data and the role of the scientific community in more comprehensively fulfilling the FDA’s promise to protect and promote public health.”

-Mike Bederka

Reference:

Xie Y, Bowe B, Li T, et al. Proton pump inhibitors and risk of incident and progression of chronic kidney disease and ESRD [published online April 14, 2016]. J Am Soc Nephrol. doi:10.1681/ASN.2015121377.