Long-term effects of in utero exposure to cyclosporin A on renal function in the rabbit.
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.
Service de Pédiatrie 2, Hôpital d'Enfants, 10 Bd Maréchal de Lattre de Tassigny, 21079 Dijon Cedex, France.
Anaïs
A
Tendron-Franzin
Jean-Bernard
JB
Gouyon
Jean-Pierre
JP
Guignard
Stéphane
S
Decramer
Eve
E
Justrabo
Thierry
T
Gilbert
Denis Salomon
DS
Semama
D000014:Abnormalities, Drug-Induced / Q000175:diagnosis / Q000209:etiology*; D000818:Animals; D000831:Animals, Newborn; D016572:Cyclosporine / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000196:embryology; D011247:Pregnancy; D011270:Pregnancy, Animal; D011297:Prenatal Exposure Delayed Effects; D011817:Rabbits; D011897:Random Allocation; D012079:Renal Circulation / Q000187:drug effects; D012307:Risk Factors; D012680:Sensitivity and Specificity; D018600:Teratology; D014655:Vascular Resistance / Q000187:drug effects
D007166:Immunosuppressive Agents; D016572:Cyclosporine