Utility of Blood Biomarkers to Predict Marrow Iron Stores in Children

Abstract

Background: Iron deficiency is common in children with kidney failure, but current guidelines are based on biomarkers of iron stores that may be influenced by inflammation. This is the first study that examined which serum iron indices were associated with stainable marrow iron stores (the gold standard) in this population with kidney failure who underwent bone biopsies. Methods: This cross-sectional study enrolled 71 clinically stable children and young adults receiving dialysis who underwent bone biopsy for chronic kidney disease-mineral bone disorder between 2007 through 2011. Bone biopsies were stained with Perls’ Prussian blue and independently interpreted by a pathologist blinded to participants’ iron parameters and clinical status. Marrow staining was scored absent vs. present to facilitate receiver operator curve (ROC) analysis. In ROC analysis, the ability of serum ferritin to detect stainable marrow iron stores was compared with that of transferrin saturation (TSAT), serum hepcidin, and clinical guideline-based iron deficiency cut-offs for serum iron, TSAT, and their combinations. Results: Mean age was 17.2 ± 4.4 years (range 2-28), and 30% of patients were female. Median dialysis vintage was 1.2 (IQR 0.7, 2.0) years, and 56% were supported by peritoneal dialysis. Mean hemoglobin was 12.4 ± 1.7 g/dl, and 35% were receiving iron supplementation at the time of biopsy. Based on the gold standard of depleted marrow iron stores, 46.5% of patients were iron-deficient. As an indicator of marrow iron staining, serum ferritin provided a higher area under the ROC curve than serum hepcidin, TSAT, or clinical guidelines-based evaluation of TSAT + ferritin. Conclusions: In this cohort of children and young adults with kidney failure, serum ferritin provided the best indication of stainable marrow iron stores, followed by transferrin saturation.