title: Renal tubular dysgenesis, a not uncommon autosomal recessive disorder leading to oligohydramnios: Role of the Renin-Angiotensin system.
abstract: Renal tubular dysgenesis is a clinical disorder that is observed in fetuses and characterized by the absence or poor development of proximal tubules, early onset and persistent oligohydramnios that leads to the Potter sequence, and skull ossification defects. It may be acquired during fetal development or inherited as an autosomal recessive disease. It was shown recently that autosomal recessive renal tubular dysgenesis is genetically heterogeneous and linked to mutations in the genes that encode components of the renin-angiotensin system. This study analyzed the clinical expression of the disease in 29 fetus/neonates from 18 unrelated families and evaluated changes in renal morphology and expression of the renin-angiotensin system. The disease was uniformly severe, with perinatal death in all cases as a result of persistent anuria and hypoxia related to pulmonary hypoplasia. Severe defects in proximal tubules were observed in all fetuses from 18 gestational weeks onward, and lesions also involved other tubular segments. They were associated with thickening of the renal arterial vasculature, from the arcuate to the afferent arteries. Renal renin expression was strikingly increased in 19 of 24 patients studied, from 13 families, whereas no renal renin was detected in four patients from three families. Angiotensinogen and angiotensin-converting enzyme were absent or present in only small amounts in the proximal tubule, in correlation with the severity of tubular abnormalities. No specific changes were detected in angiotensin II receptor expression. The severity and the early onset of the clinical and pathologic expression of the disease underline the major importance of this system in fetal kidney function and development in humans. The identification of the disease on the basis of precise histologic analysis and the research of the genetic defect now allow genetic counseling and early prenatal diagnosis.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 574, Collège de France, Paris, France.
authors.forename: Mireille
authors.initials: M
authors.lastname: Lacoste
authors.forename: Yi
authors.initials: Y
authors.lastname: Cai
authors.forename: Liliane
authors.initials: L
authors.lastname: Guicharnaud
authors.forename: Françoise
authors.initials: F
authors.lastname: Mounier
authors.forename: Yves
authors.initials: Y
authors.lastname: Dumez
authors.forename: Raymonde
authors.initials: R
authors.lastname: Bouvier
authors.forename: Frédérique
authors.initials: F
authors.lastname: Dijoud
authors.forename: Marie
authors.initials: M
authors.lastname: Gonzales
authors.forename: Jane
authors.initials: J
authors.lastname: Chatten
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Delezoide
authors.forename: Laurent
authors.initials: L
authors.lastname: Daniel
authors.forename: Madeleine
authors.initials: M
authors.lastname: Joubert
authors.forename: Nicole
authors.initials: N
authors.lastname: Laurent
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Aziza
authors.forename: Tahya
authors.initials: T
authors.lastname: Sellami
authors.forename: Hatem Ben
authors.initials: HB
authors.lastname: Amar
authors.forename: Catherine
authors.initials: C
authors.lastname: Jarnet
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Frances
authors.forename: Farida
authors.initials: F
authors.lastname: Daïkha-Dahmane
authors.forename: Aurore
authors.initials: A
authors.lastname: Coulomb
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Neuhaus
authors.forename: Bernard
authors.initials: B
authors.lastname: Foliguet
authors.forename: Pierre
authors.initials: P
authors.lastname: Chenal
authors.forename: Pascale
authors.initials: P
authors.lastname: Marcorelles
authors.forename: Jean Marie
authors.initials: JM
authors.lastname: Gasc
authors.forename: Pierre
authors.initials: P
authors.lastname: Corvol
authors.forename: Marie Claire
authors.initials: MC
authors.lastname: Gubler
mesh_terms: D001002:Anuria / Q000209:etiology; D005260:Female; D005313:Fetal Death / Q000209:etiology; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D007684:Kidney Tubules / Q000002:abnormalities* / Q000473:pathology; D008297:Male; D016104:Oligohydramnios; D011247:Pregnancy; D012084:Renin-Angiotensin System / Q000502:physiology*; D012886:Skull / Q000473:pathology