Use of proton pump inhibitors (PPIs) is associated with increased mortality risk in kidney transplant recipients (KTRs), especially among those taking high dosages, according to new research.

PPIs are commonly prescribed to prevent gastrointestinal complaints and complications of immunosuppressive medication, particularly corticosteroid therapy, after kidney transplantation. Yet PPI use is not routinely indicated in this situation, according to FDA guidelines.

In a post hoc analysis of the TransplantLines Food and Nutrition Biobank and Cohort Study including 703 stable KTRs, 398 used PPIs and 305 did not. Among users, 33.2% died during a median follow-up of 8.2 years compared with 20.3% among nonusers. In unadjusted analyses, PPI users had an 86% higher risk of all-cause mortality than nonusers, Rianne M. Douwes, MD, of the University of Groningen in The Netherlands and colleagues reported in PLOS Medicine. In an adjusted model (which incorporated demographics and donor and transplant characteristics), PPI users still had a significant 68% higher risk for death. These findings were replicated in an independent cohort of 656 kidney transplant recipients from the University Hospitals Leuven.

PPI use was significant associated with a 2.4- and 1.9-fold increased risk for death from cardiovascular and infectious causes, respectively, compared with nonuse.


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Compared with PPI nonusers, KTRs taking a high PPI dose (greater than 20 mg omeprazole equivalents per day) had a 2.1-fold increased death risk, whereas those taking a low dose had a significant 1.7-fold increased risk in crude analyses. Taking PPIs was not significantly associated with a higher risk of graft failure or kidney function decline.

“Our results might have important implications for clinical practice,” the authors stated. “The present study highlights the importance of an evidence-based indication for PPI treatment and suggests that treatment indication may need to be revisited in KTRs.”

Consequently, they added, physicians “should deliberate whether the benefits of PPI therapy outweigh the risks for each individual patient.”

As for why PPIs might increase mortality risk, the authors noted that it “is conceivable that in light of active immunosuppression and an existing high burden of atherosclerosis, PPIs might increase susceptibility to serious infections and/or accelerate atherosclerosis, leading to more pronounced shortening of life expectancy.”

Reference

Douwes RM, Gomes-Neto AW, Eisenga MF, et al. The association between use of proton-pump inhibitors and excess mortality after kidney transplantation: A cohort study [published online June 15, 2020]. PLoS Med 17(6):e1003140. doi: 10.1371/journal.pmed.1003140