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

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 (KTR). 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 KTR (≥1 year after transplantation) enrolled in the TransplantLines Biobank and Cohort Study. EXPOSURE PPI use, PPI type, PPI dosage, and duration of PPI use. OUTCOMES 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 KTR (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 KTR. PPI use might be an easily accessible target for alleviating fatigue and improving HRQoL among KTR. Further studies examining the effect of PPI exposure in this population are warranted.

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