TYPE OF PROTON PUMP INHIBITOR AND RISK OF IRON DEFICIENCY IN RENAL TRANSPLANT RECIPIENTS

Abstract Background and Aims Use of proton-pump inhibitors (PPIs) is common practice in renal transplant recipients (RTRs). Emerging data suggest several adverse effects of use of PPIs, including development of iron deficiency (ID). Although the latter has been shown with respect to PPIs, specific analyses for different types of PPIs and the associated risk of ID have not been performed. Method We used data from the TransplantLines Biobank and Cohort study, an ongoing prospective cohort study among all types of solid organ transplant recipients. For the current study, we used data from stable RTRs with a functional graft for more than 1 year post transplantation (n=795). We excluded RTRs who used any form of iron supplementation (n=54) and EPO-stimulating agents (n=24), resulting in 728 RTRs eligible for analyses. Use of PPIs was subdivided in different types of PPIs, i.e. omeprazole, esomeprazole, pantoprazole, and rabeprazole. ID was defined as TSAT<20% and ferritin <300 µg/L. Logistic regression analysis was used to assess the associations between PPIs and ID. Results We included 728 RTRs (age 56±13 years, 61% males), with a mean eGFR of 53±18 ml/min/1.73m2, a median [interquartile range] ferritin level of 96 (44 – 191) µg/L and mean TSAT of 24±10%. PPIs were used by 504 (69%) of the included RTRs, of which 398 (79%), 55 (11%), 49 (10%), and 2 (0.4%) respectively used omeprazole, pantoprazole, esomeprazole, and rabeprazole. Use of PPIs was strongly associated with ID (OR, 2.20; 95%CI 1.48 – 3.28; P<0.001), independent of adjustment for age, sex, BMI, eGFR, hs-CRP, smoking, alcohol use, use of calcineurine inhibitors, prednisolone, antiplatelet drugs, and antihypertensives. When subdividing the PPIs into the different types, both omeprazole (OR, 1.98; 95%CI 1.39 – 2.83; P<0.001) and esomeprazole (OR, 2.11; 95%CI 1.09 – 4.07; P=0.03) were independently associated with iron deficiency, whereas pantoprazole was not associated (OR, 0.89; 95%CI 0.47 – 1.70; P=0.73). Conclusion Omeprazole and esomeprazole, but not pantoprazole, are associated with an increased risk of ID. Our results are in line with previous reports that pantoprazole has the lowest potency with least increase in intragastric pH, thereby possibly interfering less with reduction of ferric to ferrous iron, and subsequently iron absorption. Future studies are warranted to confirm our present findings.