Rapamycin, cyclosporine, and perioperative donor-specific transfusions induce prolongation of cardiac allograft survival in the rat.

The effects of a subtherapeutic regimen of rapamycin (RAPA) combined with CsA and donor-specific blood transfusions (DST) were investigated in the ACI to LEW cardiac allograft model. Three protocols were studied. In protocol 1, recipients received a DST (day -1), RAPA intravenously at 0.08 mg/kg/day (day -1 to +5), and CsA intramuscularly at 5 mg/kg/day (day -1 to +1). In protocol 2, the course of CsA was extended to day +5, and in protocol 3 the treatment was further modified to include a second DST on day +3. Control groups received drug treatments alone or combined with DST or third-party blood transfusions. In all protocols, RAPA, CsA, or DSTs alone had little or no effect on graft survival. RAPA-DST or CsA-DST also had no effects beyond the ones induced by the drugs alone. In the RAPA-CsA groups, graft survivals were similar to the ones obtained with CsA alone. In contrast, in each of the protocols, the RAPA-CsA-DST treatment resulted in significant prolongation of graft survival as compared with all controls (P < 0.05). The administration of a second DST (CsA-RAPA-DSTx2) provided no additional benefits over a single DST. Lymph node cells from CsA-RAPA-DST subjects were hyporesponsive in MLR against donor cells and suppressed the proliferation of normal LEW cells in an MLR coculture assay, suggesting the presence of suppressor cells. Furthermore, in the CsA-RAPA-DST group, the anti-donor antibody response was suppressed. These data demonstrate that RAPA, CsA, and DST interact positively by inducing a clear-cut and significant prolongation of allograft survival in the rat model under conditions in which the individual components of the treatment are essentially ineffectual.

En bloc transplantation of infant and child cadaver kidneys to adult recipients.

From 1991 to 1992 eight child cadaveric kidneys were transplanted en block to adult recipients as part of a prospective study at The Mount Sinai Medical Center. Six of eight transplants came from infant donors less than two years of age. There were four technical complications. Two resulted in bilateral graft nephrectomy and return to dialysis, and two required unilateral graft nephrectomy with acceptable renal function from the single remaining kidney. At a mean follow-up of 11.8 months, overall graft survival is 75% with mean serum creatinine of 1.7 mg/dL. Of the infant transplants, 83% are functioning at a mean follow-up of 11.4 months. The average serum creatinine level for this group is 1.8 mg/dL. Our data support the use of en bloc child cadaveric kidneys, including infant donors less than two years of age. The use of this source increases the donor pool.