title: Hydroxyurea treatment decreases glomerular hyperfiltration in children with sickle cell anemia.
abstract: Glomerular hyperfiltration and microalbuminuria/proteinuria are early manifestations of sickle nephropathy. The effects of hydroxyurea therapy on these renal manifestations of sickle cell anemia (SCA) are not well defined. Our objective was to investigate the effects of hydroxyurea on glomerular filtration rate (GFR) measured by (99m)Tc-DTPA clearance, and on microalbuminuria/proteinuria in children with SCA. Hydroxyurea study of long-term effects (HUSTLE) is a prospective study (NCT00305175) with the goal of describing the long-term cellular, molecular, and clinical effects of hydroxyurea therapy in SCA. Glomerular filtration rate, urine microalbumin, and serum cystatin C were measured before initiating hydroxyurea therapy and then repeated after 3 years. Baseline and Year 3 values for HUSTLE subjects were compared using the Wilcoxon Signed Rank test. Associations between continuous variables were evaluated using Spearman correlation coefficient. Twenty-three children with SCA (median age 7.5 years, range, 2.5-14.0 years) received hydroxyurea at maximum tolerated dose (MTD, 24.4 ± 4.5 mg/kg/day, range, 15.3-30.6 mg/kg/day). After 3 years of treatment, GFR measured by (99m)Tc-DTPA decreased significantly from 167 ± 46 mL/min/1.73 m² to 145 ± 27 mL/min/1.73 m² (P = 0.016). This decrease in GFR was significantly associated with increase in fetal hemoglobin (P = 0.042) and decrease in lactate dehydrogenase levels (P = 0.035). Urine microalbumin and cystatin C levels did not change significantly. Hydroxyurea at MTD is associated with a decrease in hyperfiltration in young children with SCA.
authors.affiliation: Department of Hematology, St Jude Children's Research Hospital, Memphis, Tennessee, USA. baygun@nshs.edu
authors.forename: Banu
authors.initials: B
authors.lastname: Aygun
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Mortier
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Smeltzer
authors.forename: Barry L
authors.initials: BL
authors.lastname: Shulkin
authors.forename: Jane S
authors.initials: JS
authors.lastname: Hankins
authors.forename: Russell E
authors.initials: RE
authors.lastname: Ware
mesh_terms: D000293:Adolescent; D000419:Albuminuria / Q000209:etiology / Q000517:prevention & control; D000755:Anemia, Sickle Cell / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D000986:Antisickling Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D055316:Cystatin C / Q000097:blood; D016903:Drug Monitoring; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005921:Glomerulonephritis / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D016284:Technetium Tc 99m Pentetate; D013997:Time Factors
chemical_list: D000986:Antisickling Agents; C525030:CST3 protein, human; D055316:Cystatin C; D005319:Fetal Hemoglobin; D016284:Technetium Tc 99m Pentetate; D006918:Hydroxyurea