title: Increased urinary angiotensinogen is an effective marker of chronic renal impairment in very low birth weight children.
abstract: BACKGROUND
  Recent advancements in perinatal and neonatal care have increased the survival of preterm infants with lower birth weight and very low birth weight (VLBW; < 1,500 g) infants. Such infants are exposed to a higher risk of renal insufficiency in later life due to congenitally fewer nephrons; however, urinalysis in order to detect renal insufficiency in those infants at school age has not yet been established. The aim of the study was to assess chronic renal impairment in VLBW infants during their childhood after discharge from the neonatal intensive care unit (NICU) until adolescence using urinary angiotensinogen (uAGT).
  
  
  METHODS
  We compared serum levels of angiotensinogen (sAGT), creatinine, β2-microglobulin (sβ2MG) and cystatin C (sCysC), and urinary levels of uAGT, creatinine (uCre),β2-microglobulin (uβ2MG) and albumin between two infant groups-the VLBW group (50 children who were admitted to our NICU as infants), and a control group of 25 children who were born as full-term infants with birth weight ≥2,500 g. The median age of the VLBW group and control group infants was 60 months (range 7-135) and 57 months (range 5-144), respectively, at the time of evaluation.
  
  
  RESULTS
  In the VLBW group, sCysC levels were high (p < 0.05) and estimated glomerular filtration rate (eGFR) was low (p < 0.05). There were no significant differences in the ratios of uβ2MG to creatinine and urinary albumin to creatinine between the two groups. Although there were no differences in concentration of sAGT between the two groups (p = 0.062), the ratio of uAGT to creatinine was significantly higher in the VLBW group (p < 0.01). The examination of 19 VLBW infants (19/50) with eGFR ≤90 ml/min/1.73 m(2) showed a positive correlation between uAGT/creatinine and urinary albumin/creatinine (r = 0.531, p < 0.05). Furthermore, the analysis of correlation between the ratio of uAGT to creatinine and eGFR showed a reverse correlation in 19 VLBW infants (19/50) with eGFR ≤90 ml/min/1.73 m(2), 18 of whom had stage II chronic kidney disease and one who had stage III disease (r = -0.512, p ≤ 0.05).
  
  
  CONCLUSIONS
  uAGT is an effective marker for predicting the progression of chronic renal impairment in preterm VLBW infants after their growth. uAGT measurement is easier to conduct, less invasive and more sensitive than conventional uβ2MG or urinary albumin measurement.
authors.affiliation: Department of Neonatology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni, Shizuoka, 410-2295, Japan, nishizak@juntendo.ac.jp.
authors.forename: Naoto
authors.initials: N
authors.lastname: Nishizaki
authors.forename: Daishi
authors.initials: D
authors.lastname: Hirano
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nishizaki
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Fujinaga
authors.forename: Satoru
authors.initials: S
authors.lastname: Nagata
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ohtomo
authors.forename: Kazunari
authors.initials: K
authors.lastname: Kaneko
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000293:Adolescent; D041923:Adolescent Development; D000367:Age Factors; D000808:Angiotensinogen / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D001724:Birth Weight; D002648:Child; D002657:Child Development; D002675:Child, Preschool; D005260:Female; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight / Q000652:urine*; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D011379:Prognosis; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis* / Q000503:physiopathology / Q000652:urine; D012189:Retrospective Studies; D015854:Up-Regulation
chemical_list: C534931:AGT protein, human; D015415:Biomarkers; D000808:Angiotensinogen