The association between use of proton-pump inhibitors and excess mortality after kidney transplantation: A cohort study

Autoři: Rianne M. Douwes aff001;  António W. Gomes-Neto aff001;  Michele F. Eisenga aff001;  Elisabet Van Loon aff002;  Joëlle C. Schutten aff001;  Rijk O. B. Gans aff001;  Maarten Naesens aff002;  Else van den Berg aff001;  Ben Sprangers aff002;  Stefan P. Berger aff001;  Gerjan Navis aff001;  Hans Blokzijl aff003;  Björn Meijers aff002;  Stephan J. L. Bakker aff001;  Dirk Kuypers aff002
Působiště autorů: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands aff001;  Department of Nephrology and Renal Transplantation, University Hospitals Leuven and Nephrology & Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium aff002;  Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands aff003
Vyšlo v časopise: The association between use of proton-pump inhibitors and excess mortality after kidney transplantation: A cohort study. PLoS Med 17(6): e32767. doi:10.1371/journal.pmed.1003140
Kategorie: Research Article
doi: 10.1371/journal.pmed.1003140



Chronic use of proton-pump inhibitors (PPIs) is common in kidney transplant recipients (KTRs). However, concerns are emerging about the potential long-term complications of PPI therapy. We aimed to investigate whether PPI use is associated with excess mortality risk in KTRs.

Methods and findings

We investigated the association of PPI use with mortality risk using multivariable Cox proportional hazard regression analyses in a single-center prospective cohort of 703 stable outpatient KTRs, who visited the outpatient clinic of the University Medical Center Groningen (UMCG) between November 2008 and March 2011 ( Identifier NCT02811835). Independent replication of the results was performed in a prospective cohort of 656 KTRs from the University Hospitals Leuven (NCT01331668). Mean age was 53 ± 13 years, 57% were male, and 56.6% used PPIs. During median follow-up of 8.2 (4.7–9.0) years, 194 KTRs died. In univariable Cox regression analyses, PPI use was associated with an almost 2 times higher mortality risk (hazard ratio [HR] 1.86, 95% CI 1.38–2.52, P < 0.001) compared with no use. After adjustment for potential confounders, PPI use remained independently associated with mortality (HR 1.68, 95% CI 1.21–2.33, P = 0.002). Moreover, the HR for mortality risk in KTRs taking a high PPI dose (>20 mg omeprazole equivalents/day) compared with patients taking no PPIs (HR 2.14, 95% CI 1.48–3.09, P < 0.001) was higher than in KTRs taking a low PPI dose (HR 1.72, 95% CI 1.23–2.39, P = 0.001). These findings were replicated in the Leuven Renal Transplant Cohort. The main limitation of this study is its observational design, which precludes conclusions about causation.


We demonstrated that PPI use is associated with an increased mortality risk in KTRs, independent of potential confounders. Moreover, our data suggest that this risk is highest among KTRs taking high PPI dosages. Because of the observational nature of our data, our results require further corroboration before it can be recommended to avoid the long-term use of PPIs in KTRs.

Trial registration Identifier: NCT02811835, NCT01331668.

Klíčová slova:

Cardiovascular diseases – Death rates – diabetes mellitus – Magnesium – Platelets – Renal diseases – Renal transplantation – vitamin K


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