Long-Term Nephrotoxicity After Exposure to Cyclosporine in Utero

Shaheen, F; Al-Sulaiman, M. H.; Al-Khader, Abdullah A

doi:10.1097/00007890-199307000-00044

Cited by 67 publications

(29 citation statements)

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“…These results are in agreement with clinical studies reporting that children who are exposed in utero to CsA present a normal renal function during childhood (5)(6)(7)(8). This phenomenon could be explained by the adaptive glomerular hypertrophy (12) with subsequent glomerular hyperfiltration in single-nephron units (24).…”

Section: Nephron Reduction and Renal Functionsupporting

confidence: 91%

“…These drugs have been associated with increased incidence of spontaneous abortion, prematurity, and intrauterine growth retardation (IUGR) (2). Most clinical studies report that children who are exposed in utero to CsA have a normal development and present a normal renal function during the neonatal period (5,6) and up to the age of 7 (7,8). However, some experimental studies showed that a prenatal exposure to CsA induced a vacuolation of proximal tubular cells in rats (9,10) and an impaired distal nephron development in mice (11).…”

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confidence: 99%

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

Anaïs¹,

Gouyon²,

Guignard³

et al. 2004

Journal of the American Society of Nephrology

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Abstract. 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 CsAinduced 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.

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Section: Nephron Reduction and Renal Functionsupporting

confidence: 91%

mentioning

confidence: 99%

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

Anaïs¹,

Gouyon²,

Guignard³

et al. 2004

Journal of the American Society of Nephrology

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“…Temporary impairment of the infants' renal function may be caused by tacrolimus, as has been previously reported with cyclosporine (19,20). However, higher serum creatinine in newborn babies has been described after the pregnancies of normal women, and in part reflects the maternal creatinine (21,22) as opposed to drug damage to the infant kidneys.…”

Section: Newborn Baby Numbermentioning

confidence: 52%

Pregnancy After Liver Transplantation Under Tacrolimus1

Jain¹,

et al. 1997

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“…A few clinical reports indicated that children who were prenatally exposed to CsA exhibited normal renal function at birth (14) and during the first years of life (15,16). Although these short-term clinical data are reassuring, experimental studies are more worrying.…”

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confidence: 99%

Cyclosporin A Administration during Pregnancy Induces a Permanent Nephron Deficit in Young Rabbits

Tendron¹,

Decramer²,

Justrabo³

et al. 2003

Journal of the American Society of Nephrology

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ABSTRACT. Cyclosporin A (CsA) is an immunosuppressive agent used to prevent graft rejection and to treat autoimmune disorders. Successful pregnancies can be achieved among CsA-treated women, although it is known that CsA is nephrotoxic and crosses the human placenta. The aim of this study was to evaluate the harmlessness of CsA toward the embryonic kidney. Twenty-one pregnant rabbits were divided into four groups. Groups of six and four female animals were subjected to daily injections of 10 mg/kg per d CsA (administered subcutaneously) for 5 d, from day 14 to day 18 of gestation or from day 20 to day 24 of gestation, respectively. In the third group, five female animals received the CsA diluent (Cremophor) from day 14 to day 18 of gestation. The fourth group consisted of six untreated female animals. Pregnancy outcomes among CsA-treated does demonstrated a reduced number of living pups, which were also growth-retarded, with exposure to CsA from day 20 to day 24 of gestation. However, pups exposed to CsA from day 14 to day 18 of gestation exhibited normal fetal growth, and blood concentrations of CsA matched human data. Examinations of kidneys at birth demonstrated vacuolation of proximal and collecting tubules and ureteric bud ends. Increased glomerular volumes and decreased nephron densities suggested nephron mass reduction, which was quantitatively evaluated in 1-mo-old animals. The nephron numbers were reduced by 25 and 33% in day 14 to 18 CsA-treated and day 20 to 24 CsA-treated animals, respectively, which displayed compensatory adaptation of the existing nephrons. However, foci of segmental glomerular sclerosis were already present, which would possibly jeopardize renal function later in life.

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Long-Term Nephrotoxicity After Exposure to Cyclosporine in Utero

Cited by 67 publications

References 0 publications

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

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

Pregnancy After Liver Transplantation Under Tacrolimus1

Cyclosporin A Administration during Pregnancy Induces a Permanent Nephron Deficit in Young Rabbits

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