Effect of hydroxyurea treatment on renal function parameters: results from the
multi-center placebo-controlled BABY HUG clinical trial for infants with sickle
cell anemia.
Author(s): Alvarez O, Miller ST, Wang WC, Luo Z, McCarville MB, Schwartz GJ, Thompson B,
Howard T, Iyer RV, Rana SR, Rogers ZR, Sarnaik SA, Thornburg CD, Ware RE; BABY
HUG Investigators.
Collaborators: Driscoll C, Minniti C, Luchtman-Jones L, Martin B, Speller-Brown
B, Zimmerman S, Schultz W, Shipes S, Kelly T, Burgett S, Reed CK, Casella J,
Seaman P, Keefer J, Dixon S, Reinhardt MJ, Dejong R, Kalpatthi R, Jackson S,
Rackoff B, Kuisel L, Disco D, Faughnan L, Wynn L, Rey K, Rao S, Gonzalez RS,
Strashun AM, Toledano S, Barredo J, Hustace T, Thomas G, Estess D, McKenzie F,
Smith MG, Hogan T, Cochran C, Marshall J, Adix L, McDuffie J, McDonald R, Whelan
K, Luck L, MacDermott ML, Brown R, Osunkwo I, Herry A, Randall E, Cherry K,
Whitten-Shurney W, Murphy M, Khatib R.
Affiliation(s): Division of Pediatric Hematology, University of Miami, Miami, Florida 33136, USA.
oalvarez2@med.miami.edu
Publication date & source: 2012, Pediatr Blood Cancer. , 59(4):668-74
BACKGROUND: Children with sickle cell anemia (SCA) often develop hyposthenuria
and renal hyperfiltration at an early age, possibly contributing to the
glomerular injury and renal insufficiency commonly seen later in life. The Phase
III randomized double-blinded Clinical Trial of Hydroxyurea in Infants with SCA
(BABY HUG) tested the hypothesis that hydroxyurea can prevent kidney dysfunction
by reducing hyperfiltration.
PROCEDURE: 193 infants with SCA (mean age 13.8 months) received hydroxyurea 20
mg/kg/day or placebo for 24 months. (99m) Tc diethylenetriaminepentaacetic acid
(DTPA) clearance, serum creatinine, serum cystatin C, urinalysis, serum and urine
osmolality after parent-supervised fluid deprivation, and renal ultrasonography
were obtained at baseline and at exit to measure treatment effects on renal
function.
RESULTS: At exit children treated with hydroxyurea had significantly higher urine
osmolality (mean 495 mOsm/kg H(2) O compared to 452 in the placebo group, P =
0.007) and a larger percentage of subjects taking hydroxyurea achieved urine
osmolality >500 mOsm/kg H(2) O. Moreover, children treated with hydroxyurea had
smaller renal volumes (P = 0.007). DTPA-derived glomerular filtration rate (GFR)
was not significantly different between the two treatment groups, but was
significantly higher than published norms. GFR estimated by the Chronic Kidney
Disease in Children (CKiD) Schwartz formula was the best non-invasive method to
estimate GFR in these children, as it was the closest to the DTPA-derived GFR.
CONCLUSION: Treatment with hydroxyurea for 24 months did not influence GFR in
young children with SCA. However, hydroxyurea was associated with better urine
concentrating ability and less renal enlargement, suggesting some benefit to
renal function.
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