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

被引:81
作者
Alvarez, Ofelia [1 ]
Miller, Scott T. [2 ]
Wang, Winfred C. [3 ]
Luo, Zhaoyu [4 ]
McCarville, M. Beth [3 ]
Schwartz, George J. [5 ]
Thompson, Bruce [4 ]
Howard, Thomas [6 ]
Iyer, Rathi V. [7 ]
Rana, Sohail R. [8 ]
Rogers, Zora R. [9 ]
Sarnaik, Sharada A. [10 ]
Thornburg, Courtney D. [11 ]
Ware, Russell E. [12 ]
机构
[1] Univ Miami, Div Pediat Hematol, Miami, FL 33136 USA
[2] SUNY Downstate Kings Cty Hosp Ctr, Div Pediat Hematol, Brooklyn, NY USA
[3] St Jude Childrens Res Hosp, Div Pediat Hematol, Memphis, TN 38105 USA
[4] Clinical Trials & Surveys Corp, Owings Mills, MD USA
[5] Univ Rochester, Med Ctr, Div Pediat Hematol, Rochester, NY 14642 USA
[6] Univ Alabama Birmingham, Div Pediat Hematol, Birmingham, AL USA
[7] Univ Mississippi, Med Ctr, Div Pediat Hematol, Jackson, MS 39216 USA
[8] Howard Univ, Div Pediat Hematol, Washington, DC 20059 USA
[9] UT SW Med Ctr, Div Pediat Hematol, Dallas, TX USA
[10] Childrens Hosp Michigan, Div Pediat Hematol, Detroit, MI 48201 USA
[11] Duke Univ, Med Ctr, Div Pediat Hematol, Durham, NC USA
[12] Baylor Coll Med, Div Pediat Hematol, Houston, TX 77030 USA
基金
美国国家卫生研究院;
关键词
glomerular filtration rate; hydroxyurea; kidney function; urine osmolality; GLOMERULAR-FILTRATION-RATE; SERUM CYSTATIN-C; CHRONIC KIDNEY-DISEASE; BASE-LINE DATA; REFERENCE VALUES; YOUNG-CHILDREN; CLEARANCE; LENGTH; GFR; CREATININE;
D O I
10.1002/pbc.24100
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. 99mTc 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 H2O compared to 452 in the placebo group, P?=?0.007) and a larger percentage of subjects taking hydroxyurea achieved urine osmolality >500?mOsm/kg H2O. 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. (ClinicalTrials.gov number NCT00006400) Pediatr Blood Cancer 2012;59:668674. (c) 2012 Wiley Periodicals, Inc.
引用
收藏
页码:668 / 674
页数:7
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