This study shows that testing for anti-HLA DSA in eluates from removed kidney transplants using flow cytometry can be achieved and is highly efficient. It already suggests that both anti-class I and anti-class II HLA antibodies can be involved in CAN. Further studies are now needed to evaluate the possibility of identifying such antibodies in the eluates of transplant biopsy specimens from recipients experiencing CAN.

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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.

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.