Hemoglobin Decline in Children with Chronic Kidney Disease: Baseline Results from the Chronic Kidney Disease in Children Prospective Cohort Study

Background and objectives: The level of glomerular filtration rate at which hemoglobin declines in chronic kidney disease is poorly described in the pediatric population. Design, setting, participants, & measurements: This cross-sectional study of North American children with chronic kidney disease examined the association of glomerular filtration rate, determined by the plasma disappearance of iohexol, and hemoglobin concentration. Results: Of the 340 patients studied, the mean age was 11 4 yr, the mean glomerular filtration rate was 42 14 ml/min per 1.73 m 2 , and the mean hemoglobin was 12.5 1.5. Below a glomerular filtration rate of 43, the hemoglobin declined by 0.3 g/dl (95% confidence interval 0.2 to 0.5) for every 5-ml/min per 1.73 m 2 decrease in glomerular filtration rate. Above a glomerular filtration rate of 43 ml/min per 1.73 m 2 , the hemoglobin showed a nonsignificant decline of 0.1 g/dl for every 5-ml/min per 1.73 m 2 decrease in glomerular filtration rate. Conclusions: In pediatric patients with chronic kidney disease, hemoglobin declines as an iohexol-determined glomerular filtration rate decreases below 43 ml/min per 1.73 m 2 . Because serum creatinine–based estimated glomerular filtration rates may overestimate measured glomerular filtration rate in this population, clinicians need to be mindful of the potential for hemoglobin decline and anemia even at early stages of chronic kidney disease, as determined by current Schwartz formula estimates. Future longitudinal analyses will further characterize the relationship between glomerular filtration rate and hemoglobin, including elucidation of reasons for the heterogeneity of this association among individuals. Clin J Am Soc Nephrol 3: 457-462, 2008. doi: 10.2215/CJN.03020707 T he adverse health effects of anemia in adult and pediatric patients with chronic kidney disease (CKD) are both common and profound. Anemia has been associated with increased mortality, limitations in physical activity, and adverse effects on quality of life. Among children in the 2005 End Stage Renal Disease Clinical Performance Measures Project, 95% of 1598 prevalent pediatric patients with ESRD were anemic; 95% of patients who were receiving hemodialysis and 94% of patients who were receiving peritoneal dialysis were prescribed erythropoiesis-stimulating agents (ESA) (1). A lower prevalence of anemia is observed at earlier stages of CKD in pediatric patients. The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) stages CKD as follows: Stage 1, evidence of kidney damage with normal or increased GFR; stage 2, GFR 60 to 89 ml/min per 1.73 m 2 ; stage 3, GFR 30 to 59 ml/min per 1.73 m 2 ; stage 4, GFR 15 to 29 ml/min per 1.73 m 2 ; stage 5, GFR 15 ml/min per 1.73 m 2 or on dialysis (2). In a recent single-center, cross-sectional study of 366 children and adolescents with CKD, approximately 30% of patients with stages 1 and 2 CKD reported prevalent anemia, defined as hemoglobin 12 mg/dl or medical treatment for anemia, whereas 66% of patients with stage 3 and 93% of patients with stages 4 and 5 CKD were anemic. GFR was estimated from serum cystatin C in this study (3). The lower prevalence of anemia in patients with earlier stages of CKD suggests an association between hemoglobin and GFR. In adults, hemoglobin has been reported to decline below a GFR threshold of 40 to 60 ml/min per 1.73 m 2 as measured by the Modification of Diet in Renal Disease (MDRD) or Cockcroft-Gault equation (4,5). This association, including the existence of a “GFR threshold,” has not been clearly described in children. This study aimed to define more clearly the relationship between hemoglobin and GFR in the pediatric CKD population. To accomplish this, we used the relatively large sample size and precise measurement of GFR offered by the Chronic Kidney Disease in Children Prospective Cohort Study (CKiD).