Renal function in infants with sickle cell anemia: baseline data from the BABY HUG trial.

OBJECTIVES: To examine the feasibility and accuracy of glomerular filtration rate (GFR) measurements in infants with sickle cell anemia (SCA). STUDY DESIGN: The NHLBI/NICHD-sponsored Phase III randomized double-blinded placebo-controlled trial (BABY HUG) tests the hypothesis that hydroxyurea can prevent chronic organ damage in SCA. GFR elevation is a coprimary endpoint, measured quantitatively by technetium 99m-labeled diethylenetriaminepentaacetic acid (DTPA) plasma clearance and estimated by the Schwartz equation with height and creatinine. RESULTS: Baseline DTPA GFR measurement was attempted in 191 infants; 176 of 184 completed studies (96%) were interpretable. Average age (mean +/- 1SD) was 13.7 +/- 2.6 months. Average DTPA GFR was 125.2 +/- 34.4 (range 40.2-300.9, normal 91.5 +/- 17.8 mL/min/1.73m(2)), while Schwartz estimates were higher at 184.4 +/- 55.5 mL/min/1.73m(2). DTPA GFR was correlated with Schwartz GFR (r(2) = 0.0658, P = .0012); also with age, weight, height, and kidney volume (all P < .002); but not with hemoglobin, HbF, white blood cell count, reticulocytes, medical events, or splenic function. CONCLUSIONS: Quantitative GFR measurement is feasible but variable among infants with SCA. Schwartz GFR estimates are not highly correlated with quantitative DTPA GFR values. Baseline GFR measurements suggest that renal dysfunction in SCA, evidenced by glomerular hyperfiltration, begins during infancy.

Invasive pneumococcal infections in children with sickle cell disease in the era of penicillin prophylaxis, antibiotic resistance, and 23-valent pneumococcal polysaccharide vaccination.

Rates and severity of pneumococcal infections in children with sickle cell disease were examined before licensure of pneumococcal-conjugated vaccine (PVC). Rates of peak invasive infection rates in 1-year-old children with hemoglobin SS and mortality in those 0 to 10 years of age were 36.5 to 63.4 and 1.4 to 2.8 per 1000 person-years, respectively (>10 and 100 times as frequent as in the general population). Overall, 71% of serotyped isolates (n=80) were PVC serotypes and 71% of nonvaccine serotype strains were penicillin-sensitive. Clinical presentation in children with hemoglobin SS (n=71; more with hypotension) and hemoglobin SC (n=18; more with acute chest syndrome, otitis media) differed. Penicillin nonsusceptibility (38% of isolates) varied between geographic study sites. Penicillin prophylaxis appeared less effective against intermediate and resistant strains. Of all infected children, meningitis developed in 20% and 15% died (hemoglobin SS, n=15 and 11; hemoglobin SC, n=1 each). Factors associated with death included age >4 years (58%), serotype 19F, and not being followed by a hematologist (42% each). The pneumococcal-polysaccharide vaccine was 80.4% effective within 3 years after vaccination (95% CI, 39.7, 93.6). Children with sickle cell disease of all ages may benefit from PVC boosted with polysaccharide vaccination.