Baseline Serum Ferritin as an Exploratory Predictor of Hemoglobin Target Achievement During Esa Therapy in Children With Chronic Kidney Disease

Background: Anemia is a common complication of pediatric chronic kidney disease, CKD, and erythropoiesis-stimulating agents, ESAs, are frequently used to improve hemoglobin levels. Serum ferritin is commonly used to assess iron status, but its role as a predictor of hemoglobin target achievement during ESA therapy in children with CKD remains unclear. Aim: This study explored whether baseline serum ferritin could predict hemoglobin target achievement during ESA therapy in children with CKD. Methods: This multicenter, open-label, randomized, active-controlled trial was conducted between October 2019 and September 2020 at pediatric nephrology centers in Dhaka, Bangladesh. Children aged 1 to 18 years with CKD stages 3, 4, 5, or 5D, baseline hemoglobin 8 to <11 g/dL, TSAT >20%, and adequate baseline iron stores were randomized to receive either subcutaneous darbepoetin alfa, 0.75 µg/kg/week, or recombinant human erythropoietin beta, 100 IU/kg three times weekly. Target hemoglobin achievement was defined as at least one recorded hemoglobin value ≥11 g/dL during the 48-week follow-up. Hemoglobin response, ferritin trajectory, and receiver operating characteristic, ROC, performance of baseline ferritin were assessed. Results: All 44 randomized participants completed follow-up; 19 received darbepoetin alfa and 25 received rHuEPO beta. Baseline ferritin did not differ significantly between groups, 295.81 ± 325.89 ng/mL versus 416.45 ± 282.56 ng/mL, p=0.206. At 16 weeks, mean hemoglobin was identical in both groups, 10.53 g/dL, p=1.000. At 48 weeks, hemoglobin was higher in the darbepoetin alfa group, 11.19 ± 0.67 g/dL versus 10.75 ± 0.63 g/dL, p=0.033, with a greater mean rise from baseline, 2.64 g/dL versus 1.92 g/dL, p=0.004. Ferritin declined in both groups, but the magnitude of decline did not differ significantly. Baseline ferritin showed modest, non-significant discrimination for target hemoglobin achievement, AUC 0.631, 95% CI 0.458 to 0.804, p=0.161. The exploratory cutoff was 292 ng/mL, with sensitivity 63.2%, specificity 64.0%, PPV 63.2%, and NPV 64.0%. Conclusion: Baseline serum ferritin demonstrated limited standalone predictive value for hemoglobin target achievement during ESA therapy in children with CKD. The identified cutoff should be interpreted as hypothesis-generating rather than clinically definitive.