Hamster to rat kidney xenotransplantation. Effects of FK 506, cyclophosphamide, organ perfusion, and complement inhibition

Transplantation
H MiyazawaT E Starzl

Abstract

Hamster to rat renal xenotransplantation was performed with recipient nephrectomies. Recipients were treated beginning on day 0 with continuous FK 506 monotherapy, a 7-day or open-ended monotherapeutic course of cyclophosphamide (CP), and the two drug regimens combined. CP alone (10 mg/kg/day) prevented a xenospecific antibody response and tripled median survival of the kidney (defined as recipient death) from 6 (control) to 18.5 days whereas FK 506 alone had no effect. The drugs in combination were no better than CP alone (15 days) unless the 5-day course of CP was given at a higher dose (15 mg/kg) and started 3 days preoperatively (79 days). In further experiments, adjuvant measures were added to the minimally effective FK 506/7-day CP regimen which gave a median survival of only 15 days. In the most successful modification, intraoperative antibody depletion by the temporary transplantation of third party hamster liver or en bloc kidneys increased median survival from 15 to 34 and 48 days, respectively. An intraoperative i.v. dose administration of the anticomplement drug K76 instead of antibody depletion increased survival to 26 days. Although the events of kidney rejection were similar to those of heart xenografts and parti...Continue Reading

References

Aug 1, 1975·The Journal of Surgical Research·A KakitaJ G Fortner
Oct 1, 1992·Transplantation·P S JohnstonD J White
Jul 1, 1991·Transplantation·J van den BogaerdeD White
Apr 1, 1993·Transplantation·J R LeventhalA J Matas

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Citations

Apr 24, 1999·The Annals of Thoracic Surgery·M YeatmanR D Davis
Oct 1, 1994·Immunological Reviews·T E StarzlA W Thomson
Jan 20, 2000·Current Medical Research and Opinion·E O SchraaJ N IJzermans
Feb 15, 2000·The British Journal of Surgery·B SoinP J Friend
May 23, 1998·Annual Review of Immunology·H Auchincloss, D H Sachs

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