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This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2005121303v1 17/8/2253    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lacoste, M. Articles by Gubler, M. C. Search for Related Content PubMed PubMed Citation Articles by Lacoste, M. Articles by Gubler, M. C.

Renal Tubular Dysgenesis, a Not Uncommon Autosomal Recessive Disorder Leading to Oligohydramnios: Role of the Renin-Angiotensin System

Mireille Lacoste^*, Yi Cai^*, Liliane Guicharnaud^*, Françoise Mounier^*, Yves Dumez, Raymonde Bouvier, Frédérique Dijoud, Marie Gonzales^||, Jane Chatten^¶, Anne-Lise Delezoide^#, Laurent Daniel^**, Madeleine Joubert, Nicole Laurent, Jacqueline Aziza, Tahya Sellami^||||, Hatem Ben Amar^¶¶, Catherine Jarnet^##, Anne Marie Frances^***, Farida Daïkha-Dahmane, Aurore Coulomb, Thomas J. Neuhaus, Bernard Foliguet^||||||, Pierre Chenal^¶¶¶, Pascale Marcorelles^###, Jean Marie Gasc^****, Pierre Corvol^**** and Marie Claire Gubler^*

^* Institut National de la Santé et de la Recherche Médicale, Unité 574, Maternité, Hopital Necker-Enfants Malades, Université René Descartes, Départements d’Histo-Embryologie, ^|| Hôpital Saint Antoine, and ^# Hôpital Robert Debré, ^**** Institut National de la Santé et de la Recherche Médicale Unit 36, Collège de France, Paris, France; Départements de Pathologie, Hôpital Edouard Herriot and Hôpital Debrousse, Lyon, France; ^¶ Department of Pathology, Children’s Hospital, Philadelphia, Pennsylvania; ^** Département de Pathologie, Hôpital de la Timone, Marseille, France; Département de Pathologie, Hôtel-Dieu, Nantes, France; Département de Pathologie, Centre Hospitalier Universitaire, Dijon, France; Département de Pathologie, Hôpital Purpan, Toulouse, France; ^|||| Département de Pathologie, Hôpital Habib Bourguiba, and ^¶¶ Département de Néonatologie, Hôpital Hedi Chaker, Sfax, Tunisie, France; ^## Département de Pathologie, Centre Hospitalier Intercommunal, and ^*** Département de Génétique Médicale, Hôpital Font Pré, Toulon, France; Département de Pathologie, Hôpital de Poissy, Poissy, France; Département de Pathologie, Hôpital Antoine-Béclère, Clamart, France; University Children’s Hospital, Zurich, Switzerland; ^|||||| Secteur de foetopathologie and ^¶¶¶ Département d’Histoembryologie, Maternité Régionale A Pinard, Nancy, France; and ^### Département de Pathologie, Centre Hospitalier Universitaire, Brest, France

Address correspondence to: Dr. Marie Claire Gubler, INSERM U 574, Hôpital Necker Enfants Malades, 149 rue de Sèvres, 75743 Paris Cedex 15, France. Phone: +33-1-47-83-90-16; Fax: +33-1-44-49-02-90; E-mail: gubler{at}necker.fr

Received for publication December 16, 2005. Accepted for publication May 10, 2006.

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.

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673