Response to oral iron therapy in children with anemia of chronic kidney disease

Background: Anemia is a common complication of chronic kidney disease (CKD) and oral iron is recommended as initial therapy. However, response to iron therapy in children with non-dialysis CKD has not been formally assessed.

Methods: We reviewed medical records of pediatric patients with stages II-IV CKD followed in two New York metropolitan area medical centers between 2010 and 2020 and identified subjects who received oral iron therapy. Response to therapy at follow-up visits was assessed by improvement of hemoglobin, resolution of anemia by the 2012 KDIGO definition, and changes in iron status. Potential predictors of response were examined using regression analyses (adjusted for age, sex, eGFR, and center).

Results: Study criteria were met by 65 children (median age 12 years, 35 males) with a median time between visits of 81 days. Median eGFR was 44 mL/min/1.73 m², and 40.7% had glomerular CKD etiology. Following iron therapy, hemoglobin improved from 10.2 to 10.8 g/dL (p < 0.001), hematocrit from 31.3 to 32.8% (p < 0.001), serum iron from 49 to 66 mcg/dL (p < 0.001), and transferrin saturation from 16 to 21.4% (p < 0.001). There was no significant change in serum ferritin (55.0 to 44.9 ng/mL). Anemia (defined according to KDIGO) resolved in 29.3% of children. No improvement in hemoglobin/hematocrit was seen in 35% of children, and no transferrin saturation improvement in 26.9%. There was no correlation between changes in hemoglobin and changes in transferrin saturation/serum iron, but there was an inverse correlation between changes in hemoglobin and changes in ferritin. The severity of anemia and alkaline phosphatase at baseline inversely correlated with treatment response.

Conclusions: Anemia was resistant to 3 months of oral iron therapy in ~ 30% of children with CKD. Children with more severe anemia at baseline had better treatment response, calling for additional studies to refine approaches to iron therapy in children with anemia of CKD and to identify additional predictors of treatment response.