#2264 Efficacy and safety of oral iron supplementation with liposomal iron in non-dialysis chronic kidney disease patients with iron deficiency

Abstract

Abstract Background and Aims Iron deficiency (ID) is very common in patients with non-dialysis dependent chronic kidney disease (NDD-CKD). In these patients, oral iron supplementation is recommended as first-line treatment for ID. However, the efficacy of oral iron supplementation is frequently impaired by a higher incidence of adverse gastrointestinal side effects. Liposomal iron is a compound with ferric pyrophosphate enclosed in a phospholipid nucleus, providing high gastrointestinal absorption and bioavailability and a lower incidence of side effects. However, few data are available on its efficacy in patients with NDD-CKD. Method This single-arm pilot study was carried out in in patients with NDD-CKD stages 1-5 and ID, defined as serum ferritin (SF)<100 ng/mL and/or transferrin saturation (TSAT)< 20%, consecutively seen in two Nephrology units (Naples and Bari) from 01/12/2022 to 01/04/2023. We assessed the efficacy of six months of liposomal iron therapy in correcting ID across three visits after baseline (month 1, 3 and 6). All patients received liposomal iron (30 mg/day twice daily for the first month followed by 30 mg daily for the remaining five months). The primary endpoints were the achievement of SF ≥100 ng/mL and TSAT ≥20%. Secondary outcomes were hemoglobin (Hb) changes and safety of liposomal iron; adherence to the iron supplementation was assessed by monthly pill counting. Changes of continuous variables during the study were analyzed by linear mixed models assuming an unstructured covariance matrix; this was done to take into account the correlation between repeated measures and missing points for patients not completing the study. Change of prevalence of corrected SF and TSAT values from baseline to month 1, 3 and 6 was analyzed by McNemar test. Results 38 patients (65.3 ± 15.2 years, 52.6% males, 35.1% diabetes, eGFR 38.5 ± 28.8 mL/min/1.73 m2) received at least one dose of liposomal iron (safety population). Efficacy population included 34 patients with at least one control visit after baseline. Clinical characteristics of patients enrolled in the two clinics did not differ. In efficacy population, baseline SF was 44 (IQR 19-82) ng/mL and TSAT 14.3 ± 5.9%, corresponding to a percentage of SF<100 ng/mL of 78.9%, and TSAT<20% in 89.5%; 64.7% had both parameters below the cut-offs. Anemia (defined as Hb<12 g/dL in women and <13 g/dL in men) was detected in 22/34 patients. Liposomal iron induced a progressive increase of TSAT from 14.3 ± 5.9%, at baseline to 20.0 ± 7.6% at month-6 (P = 0.009) whereas no difference was detected for SF (Fig. 1A and 1C). Accordingly, at the end of study, the prevalence of TSAT>20% significantly increased from 11.8% to 50.0% (P = 0.002) while correction of SF, mildly improved (from 23.5% to 30.0%, P = 0.214, Fig. 1B and 1D). When patients were stratified by anemia, a significant improvement of TSAT was observed in anemic patients (from 13.3 ± 5.8% to 20.2 ± 8.1%, P = 0.012), whereas no significant improvement was found in patients without anemia (P = 0.093). Adherence to iron supplementation was 100% in patients completing the study. Hb values did not significantly increase at month-6 in either anemic (+0.60 ± 1.39 g/dL, P = 0.258) or non-anemic (+0.08 ± 0.78 g/dL, P = 1.0) patients. In safety population (n = 38), 7 patients dropped out (18.4%). In particular, treatment was discontinued in 4 patients in the first month (2 for diarrhea, 1 for dyspepsia and constipation, and 1 for death), 1 patient after 3 months (switch to intravenous iron for symptomatic anemia), and 2 after five months (1 for dyspepsia and 1 for death). Conclusion The use of liposomal iron in patients with NDD-CKD is associated with a partial correction of functional ID (TSAT<20%), with no significant effect on iron storage. The small sample size prevents any causative conclusion, though it may provide some insights into using these compounds in patients with CKD.