Serum ferritin level changes in children with sickle cell disease on chronic blood transfusion are nonlinear and are associated with iron load and liver injury.

Chronic blood transfusion is increasingly indicated in patients with sickle cell disease. Measuring resulting iron overload remains a challenge. Children without viral hepatitis enrolled in 2 trials for stroke prevention were examined for iron overload (STOP and STOP2; n = 271). Most received desferrioxamine chelation. Serum ferritin (SF) changes appeared nonlinear compared with prechelation estimated transfusion iron load (TIL) or with liver iron concentrations (LICs). Averaged correlation coefficient between SF and TIL (patients/observations, 26 of 164) was r = 0.70; between SF and LIC (patients/observations, 33 of 47) was r = 0.55. In mixed models, SF was associated with LIC (P = .006), alanine transaminase (P = .025), and weight (P = .026). Most patients with SF between 750 and 1500 ng/mL had a TIL between 25 and 100 mg/kg (72.8% +/- 5.9%; patients/observations, 24 of 50) or an LIC between 2.5 and 10 mg/g dry liver weight (75% +/- 0%; patients/observations, 8 of 9). Most patients with SF of 3000 ng/mL or greater had a TIL of 100 mg/kg or greater (95.3% +/- 6.7%; patients/observations, 7 of 16) or an LIC of 10 mg/g dry liver weight or greater (87.7% +/- 4.3%; patients/observations, 11 of 18). Although SF changes are nonlinear, levels less than 1500 ng/mL indicated mostly acceptable iron overload; levels of 3000 ng/mL or greater were specific for significant iron overload and were associated with liver injury. However, to determine accurately iron overload in patients with intermediately elevated SF levels, other methods are required. These trials are registered at www.clinicaltrials.gov as #NCT00000592 and #NCT00006182.

Prevalence, prevention, and treatment of microalbuminuria and proteinuria in children with sickle cell disease.

Microalbuminuria (MA) and proteinuria (P) are believed to be precursors of sickle cell nephropathy. We analyzed our longitudinal data on MA/P in children with sickle cell disease (SS) to define the age of onset, association with age, sex, and hemoglobin, and to explore the safety and efficacy of hydroxyurea and angiotensin converting enzyme inhibitor (ACEI) therapy. Data on 191 patients with SS (ages 3 to 20 y) with a mean follow up of 2.19 years+/-2.05 were available. Urine MA was measured yearly with follow-up testing if abnormal. Prevalence of MA/P was 19.4%. Increasing age and lower hemoglobin levels were related to MA/P but sex was not. Microalbumin excretion normalized in 44% of patients treated with hydroxyurea and 56% of patients treated with ACEI. Hyperkalemia developed in 4 ACEI patients resulting in discontinuation of treatment in 3 children. In summary, MA/P often develops in childhood and preventive and treatment strategies for sickle cell nephropathy should be a focus of pediatric programs. Our preliminary data suggest that although both hydroxyurea and ACEI therapy may be beneficial for MA/P, hyperkalemia may limit the utility of ACEI.