Association of Intravenous Versus Oral Iron Therapy With Clinical Outcomes in Patients With Advanced CKD.

Rationale & Objective: The long-term outcomes associated with intravenous (IV) versus oral iron replacement therapy in patients with chronic kidney disease are unclear. We investigated the association of IV versus oral iron replacement therapy with incident end-stage kidney disease (ESKD) and with all-cause mortality in a national cohort of US veterans with an estimated glomerular filtration rate of < 60mL/min/1.73m Study Design: A national Veterans Affairs (VA) historical cohort study. Setting & Participants: Total of 17,428 incident new users of oral iron replacement therapy and a comparable group of 879 incident new users of IV iron replacement therapy during October 1, 2004, through September 30, 2006, with longitudinal follow-up until September 30, 2019. Predictor: Incident new use of oral versus IV IRT. Outcomes: ESKD and mortality. Analytical Approach: We examined the association of oral versus IV IRT with outcomes using competing risk regression and Cox models. We used propensity score matching to account for differences in baseline characteristics. Results: Event rates were overall higher in patients receiving IV iron replacement, but the risk was mitigated after propensity scores matching, with no significant association observed between the type of iron therapy and ESKD (subhazard ratio: 1.07; 95% CI, 0.82-1.39; Limitations: Potential selection bias and residual confounding. Conclusions: In this large national cohort of patients with chronic kidney disease, IV iron was not significantly associated with a higher risk of incident ESKD and all-cause mortality when compared to oral iron therapy. The comparative effectiveness of the different iron replacement modalities will need to be studied further in clinical trials.