A life-supporting technique of renal allotransplantation in Macaca fascicularis to evaluate novel immunosuppressive drugs in nonhuman primates

J Surg Res. 2002 Sep;107(1):64-74. doi: 10.1006/jsre.2002.6499.

Abstract

Background: The use of nonhuman primates in preclinical transplantation studies is becoming more common. This report details complete procedures developed for a successful life-supporting kidney allotransplantation program using the cynomolgus monkey (Macaca fascicularis).

Materials and methods: All transplants were performed in wild-caught, ABO-matched, MLR-mismatched adult males. Transplant procedures were staggered: an animal first served as a donor, was allowed to recover for 4 weeks, and was subsequently used as a recipient. The kidney was flushed in situ while the aorta was briefly cross-clamped. The graft was implanted heterotopically end-to-side in the right iliac fossa using microsurgical techniques. An ureteroneocystostomy was constructed; a telemetry probe was inserted into the aorta, and the remaining native kidney was removed.

Results: Sixty-two transplants were performed in 6.9 +/- 0.1 kg animals. Operating times in the donor and recipient were 126 +/- 3 and 166 +/- 5 min, respectively. The cold ischemia time was 55 +/- 1 min. There were no intraoperative deaths. Postoperative complications were observed in six (9.7%) monkeys and consisted of one early renal arterial thrombosis and five ureteral complications (two of which were successfully repaired). Transplants were ultimately successful in 93.6% (58/62) of cases. Immediate kidney function was satisfactory, with a mean serum creatinine of 1.7 +/- 0.2 mg/dL and a mean urine output of 140 +/- 15 ml on postoperative day 7.

Conclusion: Life-supporting kidney transplantation in cynomolgus macaques is a demanding operation that requires great attention to details. Precise surgical techniques, telemetric monitoring, ultrasound surveillance, and aggressive, early, postoperative fluid resuscitation produced a 94% success rate.

MeSH terms

  • Animals
  • Diuresis
  • Drug Evaluation / methods
  • Immunosuppressive Agents / therapeutic use*
  • Kidney / pathology
  • Kidney / physiopathology
  • Kidney Transplantation* / adverse effects
  • Life Support Care*
  • Macaca fascicularis
  • Male
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Immunosuppressive Agents