1. PPI use may be associated with an increased mortality risk in patients who have received kidney transplants.
Evidence Rating Level: 1 (Excellent)
Proton-pump inhibitors (PPIs) are commonly prescribed to kidney transplant recipients (KTRs) to protect against gastrointestinal symptoms and complications induced by their immunosuppressive therapy. Although PPIs are generally well-tolerated, numerous observational studies have demonstrated that chronic PPI use is associated with adverse health outcomes, such as increased nutritional deficiencies. A post hoc analysis of the TransplantLines Food and Nutrition Biobank and Cohort Study, a longitudinal study of American veterans (n= 349 312, median followup= 8.2years), found an increased mortality risk in PPI users compared to nonusers (n=703 KTRs, HR 1.86, P<0.001). This association remained independent after adjusting for potential confounding variables, such as medication use and comorbidities (HR 1.68, P=0.002). Specifically, PPI use was associated with an increased risk of mortality from cardiovascular causes (HR 2.42, P<0.001). Subgroup analyses also showed that this association appears to be dose dependent, with premature mortality highest in KTRs taking more than 20mg omeprazole equivalents/day (Ptrend<0.001). The results of their replication study, using an independent cohort of stable KTRS from University Hospitals Leuven (n=329, median followup= 3.7 years), showed similar results to those in the TransplantLines study. Prospective analyses showed PPI users had over twice the mortality risk of nonusers (HR 2.47, P<0.001), which remained significant after adjusting for potential confounders (HR 1.75, P=0.01). Further research is needed to fully elucidate whether there is a a cause-effect relationship between PPI use and its association with increased mortality risk in KTRs (i.e. conducting an RCT), and if it exists, by what mechanism.
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