MO523: The Differential Effect of Third-Generation Intravenous Iron Preparations (Ferric Carboxymaltose, Ferric Derisomaltose) on Hematinic and Renal Function Variables in Patients With Non-Dialysis Dependent CKD and Iron Deficiency Anemia
Authors: Kassianides Xenophon , Bhandari Sunil 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Iron deficiency anemia is common in patients with non-dialysis dependent chronic kidney disease (CKD). Guidelines advocate the use of oral or intravenous (IV) iron, with IV iron offering a quicker and potentially more efficacious replenishment. The advent of third-generation IV iron products [such as ferric carboxymaltose (FCM) and ferric derisomaltose (FDI)] has allowed high doses of iron to be provided in a single sitting. Despite good evidence on their efficacy in replenishing iron stores and safety in terms of renal injury and inflammation when compared against placebo, oral iron or older iron compounds (such as iron sucrose and low molecular weight iron dextran), the two compounds have never before been compared head-to-head in CKD.

METHOD
As part of the single-center double-blinded exploratory randomized controlled trial ‘Iron and Phosphaturia—ExplorIRON-CKD’ that took place in a tertiary center in the UK, patients with iron deficiency with/without anemia and CKD stage 3a–5 but not on dialysis were recruited to receive FCM or FDI in two divided doses—1000 mg at baseline and 500–1000 mg in a 1-month interval to achieve replenishment. Iron deficiency was defined as serum ferritin (SF) &lt;200 µg/L or transferrin saturation (TSAT) ≤20% and SF 200–299 µg/L. Markers of treatment response such as hemoglobin and iron parameters [serum ferritin (SF), transferrin saturation (TSAT)], renal function and injury [serum creatinine, estimated glomerular filtration rate (eGFR) and protein: creatinine ratio (PCR)] and inflammation (CRP) were monitored throughout the study. Hemoglobin, renal function and inflammation were monitored at baseline, 2 weeks, 1 month and 2 months following initial infusion. Iron response was assessed at baseline, 1–2 days, 2 weeks, 1 month post-initial infusion (and time of second infusion), 1–2 days after the second infusion and 2 months after initial administration.

RESULTS
A total of 26 patients were recruited; 14 were randomized to receive FDI and 12 to receive FCM. All patients received at least one iron dose (1000 mg), 10 patients received two FDI doses and 11 received two FCM doses. There was an increase in hemoglobin in both groups, with no significant difference between the groups at any given time point in the study [baseline: FDI: 99.2 (12.2) g/L versus FCM: 101.6 (15.3) g/L; P = .67; 2 months: FDI: 106.0 (13.3) g/L versus FCM: 109.1 (8.3) g/L; P = .526). Both groups had a median baseline SF &lt;100 µg/L and TSAT &lt;20%, and by the end of follow-up, iron repletion was similarly successful in both groups as indicated by a median SF &gt; 400 µg/L and a TSAT &gt;20% (Figure 1). A small numerical reduction was noted in median eGFR in the FCM group from baseline to the end of the study (baseline: 18.0 (11.3) mL/min/1.73 m2 versus 2 months: 16.5 (8.5) mL/min/1.73 m2); however, there was no significant difference between the two groups at any time point in the study (Figure 2). Urinary PCR, serum creatinine and CRP remained stable throughout the study and did not differ significantly between the two groups.

CONCLUSION
Third-generation IV iron preparations are efficacious in replenishing iron stores. There was no adverse short-term impact on renal function, injury or inflammation. In our cohort, the two compounds were equivocal for the parameters studied, with no significant difference identified in any of the areas examined. The population was small, therefore the results should be interpreted with caution; nonetheless, newer IV iron compounds appear to be equally efficacious in the treatment of iron deficiency anemia in non-dialysis-dependent CKD.