Proton Pump Inhibitors and Hyporesponsiveness to Erythropoiesis-Stimulating Agents in Hemodialysis Patients: Results from the Japan Dialysis Outcomes and Practice Patterns Study

Abstract

<b><i>Introduction:</i></b> Hyporesponsiveness to erythropoiesis stimulating agents (ESAs) is important problem in dialysis patients. While proton pump inhibitors (PPIs) may inhibit iron absorption, few studies have examined associations between PPIs and ESA-resistant anemia in hemodialysis patients. This study examined the associations between PPIs and ESA-resistant anemia in hemodialysis patients. <b><i>Methods:</i></b> The present study was a cross-sectional study using repeated 4-month observations, up to eight observations/patient, from the Japan Dialysis Outcomes and Practice Patterns Study (J-DOPPS). The primary outcome was erythropoietin resistance index (ERI). ESA dose, hemoglobin, proportion of erythropoietin-resistant anemia, transferrin saturation (TSAT), and ferritin were also examined. Linear or risk-difference regression models were used with generalized estimating equations to account for repeated measurements. <b><i>Results:</i></b> Of 1,644 patients, 867 patients had PPI prescriptions (52.7%). Patients prescribed PPI had higher ERI, higher ESA dose, and lower TSAT levels. Multivariable analysis for 12,048 four-month observations showed significantly greater ERI in PPI users (adjusted difference 0.95 IU/week/kg/[g/dL] [95% CI: 0.40–1.50]). Significant differences were also found in ESA dose (336 IU/week [95% CI: 70–602]) and the prevalence of erythropoietin-resistant anemia (3.9% [2.0–5.8%]) even after adjusted for TSAT and ferritin. Among possible mediators between the association of PPIs and anemia, TSAT was significantly different between PPI users and non-users (adjusted difference, −0.82% [95% CI: −1.56 to −0.07]). <b><i>Conclusions:</i></b> This study showed the associations between PPI and ERI, ESA dose, and TSAT in hemodialysis patients; physicians should consider anemia’s associations with PPIs in hemodialysis patients.