Abstract
Proton-pump inhibitor (PPI) use may influence intestinal iron absorption. Low iron status and iron deficiency (ID) are frequent medical problems in renal transplant recipients (RTR). We hypothesized that chronic PPI use is associated with lower iron status and ID in RTR. Serum iron, ferritin, transferrin saturation (TSAT), and hemoglobin were measured in 646 stable outpatient RTR with a functioning allograft for ≥ 1 year from the “TransplantLines Food and Nutrition Biobank and Cohort Study” (NCT02811835). Median time since transplantation was 5.3 (1.8–12.0) years, mean age was 53 ± 13 years, and 56.2% used PPI. In multivariable linear regression analyses, PPI use was inversely associated with serum iron (β = −1.61, p = 0.001), natural log transformed serum ferritin (β = −0.31, p < 0.001), TSAT (β = −2.85, p = 0.001), and hemoglobin levels (β = −0.35, p = 0.007), independent of potential confounders. Moreover, PPI use was independently associated with increased risk of ID (Odds Ratio (OR): 1.57; 95% Confidence Interval (CI) 1.07–2.31, p = 0.02). Additionally, the odds ratio in RTR taking a high PPI dose as compared to RTR taking no PPIs (OR 2.30; 95% CI 1.46–3.62, p < 0.001) was higher than in RTR taking a low PPI dose (OR:1.78; 95% CI 1.21–2.62, p = 0.004). We demonstrated that PPI use is associated with lower iron status and ID, suggesting impaired intestinal absorption of iron. Moreover, we found a stronger association with ID in RTR taking high PPI dosages. Use of PPIs should, therefore, be considered as a modifiable cause of ID in RTR.
Highlights
Iron deficiency (ID) is very common in renal transplant recipients (RTR), with reported prevalence of 20% to 30% more than 12 months after transplantation [1,2,3]
Diabetes was more prevalent in RTR using pump inhibitor (PPI) and PPI users had higher glucose and hemoglobin A1c (HbA1c) levels, and lower levels of hemoglobin, iron, ferritin, and transferrin saturation (TSAT)
We demonstrated that PPI use is associated with lower iron status and ID, indicating impaired intestinal absorption of iron potentially related to reduced gastric acid secretion
Summary
Iron deficiency (ID) is very common in renal transplant recipients (RTR), with reported prevalence of 20% to 30% more than 12 months after transplantation [1,2,3]. It is postulated that PPIs interfere with the absorption of iron in the duodenum, where non-heme iron is primarily absorbed in its ferrous form (Fe2+) after the reduction from its less absorbable ferric form (Fe3+), which is facilitated by gastric acid and membrane reductases localized at the apical membrane of the enterocytes [12,13] This hypothesis is supported by a study from Ajmera et al, who found a reduced response to oral supplementation of ferrous sulfate in iron deficient patients taking omeprazole [14]. In a large population-based case-control study, an increased risk of ID was found among patients receiving PPI therapy for at least one year and even among intermittent long-term PPI users compared to PPI non-users [8] These findings are in line with previous results from another large cohort study in the United States, which demonstrated a higher risk of ID among chronic users of both PPIs and H2-receptor antagonists (H2RAs), which diminished after treatment discontinuation [9]
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