Proton Pump Inhibitor Use, Fatigue, and Health-Related Quality of Life in Kidney Transplant Recipients: Results From the TransplantLines Biobank and Cohort Study

Tim J. Knobbe*, Daan Kremer, TransplantLines Investigators, Rianne M. Douwes, Michele F. Eisenga, António W. Gomes-Neto, Coby Annema, J. Casper Swarte, Frank Klont, Gerjan Navis, Stefan P. Berger, Stephan J.L. Bakker, Hans Blokzijl, Frank A.J.A. Bodewes, Marieke T. de Boer, Kevin Damman, Martin H. de Borst, Arjan Diepstra, Gerard Dijkstra, Caecilia S.E. DoorenbosMichiel E. Erasmus, C. Tji Gan, Eelko Hak, Bouke G. Hepkema, Henri G.D. Leuvenink, Willem S. Lexmond, Vincent E. de Meijer, Hubert G.M. Niesters, L. Joost van Pelt, Robert A. Pol, Robert J. Porte, Adelta V. Ranchor, Jan Stephan F. Sanders, Marion J. Siebelink, Riemer J.H.J.A. Slart, Daan J. Touw, Marius C. van den Heuvel, Coretta van Leer-Buter, Marco van Londen, Erik A.M. Verschuuren, Michel J. Vos, Rinse K. Weersma

*Corresponding author for this work

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Abstract

Rationale & Objective: Prior studies report that the use of proton pump inhibitors (PPIs) can adversely affect gut microbiota and gastrointestinal uptake of micronutrients, in particular iron and magnesium, and are used frequently by kidney transplant recipients. Altered gut microbiota, iron deficiency, and magnesium deficiency have been implicated in the pathogenesis of chronic fatigue. Therefore, we hypothesized that PPI use may be an important and underappreciated cause of fatigue and reduced health-related quality of life (HRQoL) in this population. Study Design: Cross-sectional study. Setting & Participants: Kidney transplant recipients (≥1 year after transplantation) enrolled in the TransplantLines Biobank and Cohort Study. Exposure: PPI use, PPI type, PPI dosage, and duration of PPI use. Outcome: Fatigue and HRQoL, assessed using the validated Checklist Individual Strength 20 Revised questionnaire and Short Form-36 questionnaire. Analytical Approach: Logistic and linear regression. Results: We included 937 kidney transplant recipients (mean age 56 ± 13 years, 39% female) at a median of 3 (1-10) years after transplantation. PPI use was associated with fatigue severity (regression coefficient 4.02, 95% CI, 2.18 to 5.85, P < 0.001), a higher risk of severe fatigue (OR 2.05, 95% CI, 1.48 to 2.84, P < 0.001), lower physical HRQoL (regression coefficient −8.54, 95% CI, −11.54 to −5.54, P < 0.001), and lower mental HRQoL (regression coefficient −4.66, 95% CI, −7.15 to −2.17, P < 0.001). These associations were independent of potential confounders including age, time since transplantation, history of upper gastrointestinal disease, antiplatelet therapy, and the total number of medications. They were present among all individually assessed PPI types and were dose dependent. Duration of PPI exposure was only associated with fatigue severity. Limitations: Residual confounding and inability to assess causal relationships. Conclusions: PPI use is independently associated with fatigue and lower HRQoL among kidney transplant recipients. PPI use might be an easily accessible target for alleviating fatigue and improving HRQoL among kidney transplant recipients. Further studies examining the effect of PPI exposure in this population are warranted. Plain-Language Summary: In this observational study, we investigated the association of proton pump inhibitors with fatigue and health-related quality of life among kidney transplant recipients. Our data showed that proton pump inhibitors were independently associated with fatigue severity, severe fatigue, and lower physical and mental health-related quality of life. These associations were present among all individually assessed proton pump inhibitor types and were dose dependent. While we await future studies on this topic, proton pump inhibitor use might be an easily accessible target for alleviating fatigue and improving health-related quality of life among kidney transplant recipients.

Original languageEnglish
Pages (from-to)189-201.e1
JournalAmerican Journal of Kidney Diseases
Volume82
Issue number2
DOIs
Publication statusPublished - Aug 2023

Bibliographical note

Funding Information:
The TransplantLines Biobank and Cohort study was supported by a grant from Astellas BV (TransplantLines Biobank and Cohort study) and Chiesi Pharmaceuticals BV (PA-SP/ PRJ-2020-9136 ), and co-financed by the Dutch Ministry of Economic Affairs and Climate Policy by means of the PPP-allowance made available by the Top Sector Life Sciences & Health to stimulate public-private partnerships. Dr Douwes was supported by NWO / TTW in a partnership program with DSM, Animal Nutrition and Health, the Netherlands; project number 14939. The funders had no role in the study design, data collection, analysis, reporting, or the decision to submit for publication.

Publisher Copyright: © 2023 The Authors

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