Indeed, CKD has been characterized as a state of chronic low-grade inflammation, 7 and adult patients with CKD-anemia show upregulation of proinflammatory cytokines. Recently, it was recognized that CKD-anemia shares important features with anemia of inflammation. The pathogenesis of renal anemia (CKD-anemia) includes dysfunction of the erythropoietin (Epo) axis, decreased red blood cell (RBC) life span, impact of nutritional factors, and both occult and iatrogenic blood losses, among other factors. 5 The presence of anemia at initiation of dialysis is associated with higher risk of death in children. 3 Anemia negatively affects quality of life in children with CKD 4 and increases risk of hospitalization.

1, 2 Anemia complicates CKD in more than 50% of children before they reach end-stage renal disease. The association between IL-6 and hemoglobin in children with CKD remained significant after adjustment for CKD stage, iron therapy, and hepcidin.ĬKD in children is associated with significant morbidity, mortality, and high economic burden. Cytokine profiling in a pediatric CKD cohort demonstrated that of 10 cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, tumor necrosis factor (TNF)-α, and interferon-γ), only IL-6 was significantly (inversely) associated with hemoglobin when adjusted for glomerular filtration rate (GFR). Indeed, Il6 deletion mitigated the severity of renal fibrosis and alleviated relative erythropoietin insufficiency in CKD mice. However, correction of hypoferremia by oral iron supplementation in WT-CKD mice did not fully replicate the protective effects of Il6 deletion, suggesting an additional iron-independent role for IL-6 in CKD-anemia. This effect was associated with improvement of hypoferremia by Il6 deletion, likely mediated by hepcidin. IL-6 deficiency resulted in a significant improvement of red blood cell count and hemoglobin in CKD mice. WT-CKD mice developed anemia despite increases in serum erythropoietin and displayed low serum iron and elevated serum IL-6.

Hemoglobin and hematocrit levels ati