title: Renal function in angiotensinogen gene-mutated renal tubular dysgenesis with glomerular cysts.
abstract: BACKGROUND
  Inherited renal tubular dysgenesis (RTD) is caused by mutations in the genes encoding the components of the renin-angiotensin system (RAS). RTD is characterized by oligohydramnios, renal failure, neonatal hypocalvaria, and severe hypotension. The histological characteristics, underlying mechanism, and long-term prognosis remain poorly known.
  
  
  METHODS
  We describe here a 4-year-old female with RTD. Endocrinologic analysis showed a discrepancy between low plasma renin activity and high active renin concentration, suggesting a loss of the renin substrate, angiotensinogen (AGT). Direct sequencing revealed a frameshift deletion at nucleotide 1,355 in exon 5 in the AGT gene. Although a histological hallmark is regarded to be the absence or poor development of the proximal tubule, the patient does have minimally impaired function of the proximal tubule. Glomerular cysts without glomerular tufts were noted in approximately half of the glomeruli. The urinary concentrating ability and sodium reabsorption and potassium excretion in the distal nephron were severely affected.
  
  
  CONCLUSIONS
  The patient has an impaired function of the distal nephron despite minimally affected function of the proximal tubule, probably attributed to renal tubular dysgenesis and fetal hypoperfusion. The renal tubular maturity and the severity of ischemic injury may be key determinants of the clinical symptoms and pathological findings in RTD, in which the RAS plays an important role.
authors.affiliation: Department of Pediatrics, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan, satohibino@yahoo.co.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hibino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Abe
authors.forename: Akira
authors.initials: A
authors.lastname: Hojo
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Uematsu
authors.forename: Takashi
authors.initials: T
authors.lastname: Sekine
authors.forename: Kazuo
authors.initials: K
authors.lastname: Itabashi
mesh_terms: D000808:Angiotensinogen / Q000235:genetics*; D002675:Child, Preschool; D003560:Cysts / Q000473:pathology; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D007678:Kidney Glomerulus / Q000473:pathology*; D007687:Kidney Tubules, Proximal / Q000002:abnormalities* / Q000503:physiopathology; D009154:Mutation; D014564:Urogenital Abnormalities / Q000235:genetics* / Q000503:physiopathology*
chemical_list: D000808:Angiotensinogen