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Long-Term Effects of In Utero Exposure to Cyclosporin A on Renal Function in the Rabbit

Anaïs Tendron-Franzin^*, Jean-Bernard Gouyon^*, Jean-Pierre Guignard, Stéphane Decramer^*, Eve Justrabo^*, Thierry Gilbert and Denis Salomon Semama^*

*Service de Pédiatrie 2, UPRES EA 563, Dijon, France; Laboratoire de Néphrologie du développement, C.H.U.V., Lausanne, Suisse; Inserm U574, Hôpital Necker-Enfants Malades, Paris, France

Correspondence to Dr. Denis S. Semama, Service de Pédiatrie 2, Hôpital d’Enfants, 10 Bd Maréchal de Lattre de Tassigny, 21079 Dijon Cedex, France. Phone: 33-3-80-29-33-57; Fax: 33-3-80-29-38-03; E-mail: denis.semama{at}chu-dijon.fr

The number of pregnant women who receive cyclosporin A (CsA) after transplantation or for autoimmune disease has increased. CsA and its metabolites can cross the placental barrier and thus interfere with fetal development. It was shown previously that rabbits that were exposed in utero to 10 mg/kg per d CsA from the 14th to the 18th day of gestation presented a 25% nephron reduction. Thus, this study was conducted to assess the long-term systemic and renal effects of a CsA-induced nephron reduction. Twenty-two pregnant New Zealand white rabbits were randomly divided into two groups: Twelve received 10 mg/kg per d CsA from day 14 to day 18 of gestation, and 10 were used as controls. Rabbits that were born to these animals were evaluated at 4, 11, 18, and 35 wk of life. Pups that were exposed antenatally to CsA presented first a permanent nephron deficit; second, glomerular, tubular, and intrarenal hemodynamics dysfunction; third, enlarged kidneys with numerous tubular and glomerular lesions; and, fourth, an endothelin-dependent systemic hypertension that worsened with age. In utero exposure to CsA induced a nephron reduction that led to systemic hypertension and progressive chronic renal insufficiency in adulthood. A long-term clinical survey is mandatory in infants who are born to mothers who were treated with cyclosporin during pregnancy.

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