Association between common iron store markers and hemoglobin in children with chronic kidney disease

Abstract

Background: Serum ferritin and transferrin saturation (TSAT) are used to assess iron status in children with chronic kidney disease (CKD), but their sensitivity in identifying those at risk of lower hemoglobin (HGB) values is unclear.

Methods: We assessed the association of iron status markers (ferritin, TSAT, and serum iron) with age- and gender-related HGB percentile in mild-to-moderate CKD in 304 children in the Chronic Kidney Disease in Children (CKiD) Study. Standardized HGB percentile values were examined by KDOQI-recommended ferritin (≥ 100 ng/ml) and TSAT (≥ 20 %) thresholds. Regression tree methods were used to identify iron status markers and clinical characteristics most associated with lower HGB percentiles.

Results: The cohort was 62 % male, 23 % African American, and 12 % Hispanic, median age 12 years, and median HGB 12.9 g/dl. 34 % had low TSAT and 93 % low ferritin as defined by KDOQI. Distribution of HGB percentile values was lower in those with ferritin ≥ 100 ng/ml, while TSAT ≥ 20 % was associated with only modest increase in HGB percentile. In regression tree analysis, lower glomerular filtration rate (GFR), serum iron <50 μg/dl and ferritin ≥ 100 ng/ml were most strongly associated with lower HGB percentile.

Conclusions: The level of GFR was significantly associated with HGB. Higher serum ferritin was associated with lower HGB in this cohort. Low serum iron in the context of normal/increased ferritin and low HGB may be a useful indicator of iron-restricted erythropoiesis.

Fig. 1

Distribution of iron biomarker values by stage of chronic kidney disease in 304 iron- and erythropoiesis stimulating agent-naive enrolled in the Chronic Kidney Disease in Children (CKiD) Study

Fig. 2

Percentile plots of hemoglobin z-score (for age, sex, and race) by Disease Outcomes Quality Initiative (KDOQI) recommended thresholds for ferritin and transferrin saturation (TSAT) in 304 iron supplement- and erythropoiesis stimulating agent-naive children. Horizontal lines of each percentile plot indicate the strata-specific percentiles of hemoglobin z-score indicated on the left. Outliers (values < the 2.5 percentile or > the 97.5 percentile) are shown as solid dots. The proportion of each hemoglobin z-score distribution corresponding to standardized hemoglobin levels less than the 5th percentile (z-score < −1.64) is shaded in gray

Fig. 3

Regression tree analysis examining factors predictive of hemoglobin percentile value in 304 iron supplement- and erythropoiesis stimulating agent-naive children. Each pair of solid black arrows represents binary partitioning of the hemoglobin percentile values by the independent variable described in the resulting two boxes. The p value between the two boxes quantifies the statistical significance of the difference in hemoglobin percentile values by the partition. Dashed red lines represent amalgamations of subgroups (resulting from the partitioning process) with similar hemoglobin percentile distributions. Ovals at the bottom of the tree describe the final three unique subgroups of hemoglobin percentile (number of subjects, median [IQR] of hemoglobin percentiles) identified from the analysis. GFR glomerular filtration rate (ml/min/1.73 m²), sFE serum iron (μg/dl), ferritin units = ng/ml