Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen.
Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen.
Am J Kidney Dis. 2023 Aug;82(2):189-201.e1. doi: 10.1053/j.ajkd.2022.12.012. Epub 2023 Feb 18.
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.
Cross-sectional study.
SETTING & PARTICIPANTS: Kidney transplant recipients (≥1 year after transplantation) enrolled in the TransplantLines Biobank and Cohort Study.
PPI use, PPI type, PPI dosage, and duration of PPI use.
Fatigue and HRQoL, assessed using the validated Checklist Individual Strength 20 Revised questionnaire and Short Form-36 questionnaire.
Logistic and linear regression.
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.
Residual confounding and inability to assess causal relationships.
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.
先前的研究报告称，质子泵抑制剂（PPIs）的使用会对肠道微生物群产生不利影响，并影响胃肠道对微量元素（尤其是铁和镁）的吸收，而这些元素在肾移植受者中经常使用。肠道微生物群的改变、缺铁和缺镁与慢性疲劳的发病机制有关。因此，我们假设 PPI 的使用可能是导致该人群疲劳和健康相关生活质量（HRQoL）下降的一个重要但未被充分认识的原因。
横断面研究。
参加 TransplantLines 生物库和队列研究的肾移植受者（移植后≥1 年）。
PPI 使用、PPI 类型、PPI 剂量和 PPI 使用持续时间。
我们纳入了 937 名肾移植受者（平均年龄 56±13 岁，39%为女性），在移植后中位数为 3（1-10）年。PPI 使用与疲劳严重程度相关（回归系数 4.02，95%CI，2.18 至 5.85，P<0.001），发生严重疲劳的风险更高（OR 2.05，95%CI，1.48 至 2.84，P<0.001），身体 HRQoL 更低（回归系数-8.54，95%CI，-11.54 至-5.54，P<0.001），心理 HRQoL 更低（回归系数-4.66，95%CI，-7.15 至-2.17，P<0.001）。这些关联独立于潜在的混杂因素，包括年龄、移植后时间、上消化道疾病史、抗血小板治疗和药物总数。它们存在于所有单独评估的 PPI 类型中，并且与剂量有关。PPI 暴露时间仅与疲劳严重程度相关。
残留混杂因素和无法评估因果关系。
PPI 的使用与肾移植受者的疲劳和较低的 HRQoL 独立相关。PPI 的使用可能是缓解肾移植受者疲劳和改善 HRQoL 的一个容易接近的目标。需要进一步研究来评估该人群中 PPI 暴露的影响。
