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Renal function in infants with sickle cell anemia: baseline data from the BABY HUG trial
Russell E Ware1, Renee C Rees, Sharada A Sarnaik
1St. Jude Children's Research Hospital, Memphis, TN 38105, USA. russell.ware@stjude.org
Insights
Glomerular filtration rate (GFR) measurement is feasible in infants with sickle cell anemia (SCA). However, quantitative DTPA GFR values show variability and are not well-correlated with Schwartz estimates, indicating early renal dysfunction.
Area of Science:
- Pediatric Nephrology
- Hematology
- Clinical Trials
Background:
- Sickle cell anemia (SCA) is a genetic blood disorder associated with chronic organ damage.
- Early detection of renal dysfunction is crucial for managing SCA complications.
- Glomerular filtration rate (GFR) is a key indicator of kidney function.
Purpose of the Study:
- To assess the feasibility and accuracy of measuring GFR in infants with SCA.
- To compare quantitative GFR measurements with estimated GFR values in this population.
Main Methods:
- Utilized data from the BABY HUG Phase III clinical trial.
- Measured GFR quantitatively using technetium 99m-labeled diethylenetriaminepentaacetic acid (DTPA) plasma clearance.
- Estimated GFR using the Schwartz equation based on height and creatinine.
Main Results:
- Quantitative GFR measurement was feasible in 96% of infants studied.
- Average DTPA GFR was 125.2 mL/min/1.73m(2), while Schwartz estimates were higher at 184.4 mL/min/1.73m(2).
- DTPA GFR showed significant correlations with age, weight, height, and kidney volume, but not with SCA-specific biomarkers or clinical events.
Conclusions:
- Quantitative GFR measurement is achievable in infants with SCA, though results exhibit variability.
- Schwartz equation estimates do not strongly correlate with quantitative DTPA GFR measurements in this age group.
- Findings suggest that glomerular hyperfiltration, an early sign of renal dysfunction, is present in infants with SCA.
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.
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