Schmiedt Chad, Penzo Chiara, Schwab Michelle, Dubielzig Richard, McAnulty Jonathan
Department of Surgical Sciences, College of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706-1102, USA.
Vet Surg. 2006 Feb;35(2):113-24. doi: 10.1111/j.1532-950X.2006.00122.x.
To investigate the use of a capecitabine (CAP)-based regimen after renal transplantation in dogs.
Prospective, pilot study.
Healthy, unrelated, dog erythrocyte antigen (DEA)-matched, adult beagles.
Standard heterotopic renal transplantation with native nephrectomy was performed in 7 dogs. Dogs received oral, twice daily, CAP (250 mg/m2), cyclosporine-A (CsA) (4 mg/kg), ketoconazole (5 mg/kg), and prednisolone (0.25 mg/kg). After 90 days the surviving dogs were euthanatized and complete necropsy was performed.
Seven transplants were performed. All dogs survived surgery. Six dogs had acute neurotoxicity, which resulted in death or euthanasia of 2 dogs within 2 days of surgery. In the remaining dogs, toxicity resolved rapidly with cessation of drug administration. Thereafter, modification of the regimen minimized toxicity. The 5 remaining dogs survived to study end; 4 dogs had no evidence of graft rejection. Necropsy examination was mostly unremarkable in all dogs. There were no major changes in CBC or biochemical values, except for a significant increase in serum calcium.
CAP appeared well tolerated in most dogs. Toxicity occurred but abated with modification of the drug regimen. Efficacy for postoperative immunosuppression cannot be determined by this study, although results are promising.
CAP-CsA-prednisolone is an effective, oral immunosuppressive regimen for prevention of acute allograft rejection in DEA-matched beagles. Further studies on dose, toxicity, and efficacy compared with current immunosuppressive regimens are needed before use in clinical practice.
研究以卡培他滨(CAP)为基础的方案在犬肾移植后的应用。
前瞻性试点研究。
健康、无亲缘关系、犬红细胞抗原(DEA)匹配的成年比格犬。
对7只犬进行标准的异位肾移植并切除自体肾。犬每日口服两次CAP(250mg/m²)、环孢素A(CsA)(4mg/kg)、酮康唑(5mg/kg)和泼尼松龙(0.25mg/kg)。90天后,对存活的犬实施安乐死并进行完整的尸检。
进行了7次移植。所有犬均存活至手术结束。6只犬出现急性神经毒性,导致2只犬在手术后2天内死亡或实施安乐死。其余犬在停药后毒性迅速消退。此后,调整方案使毒性降至最低。其余5只犬存活至研究结束;4只犬无移植排斥迹象。所有犬的尸检结果大多无异常。血常规或生化指标无重大变化,血清钙显著升高除外。
大多数犬对CAP耐受性良好。虽出现毒性,但通过调整药物方案得以减轻。尽管结果有前景,但本研究无法确定术后免疫抑制的疗效。
CAP-CsA-泼尼松龙是预防DEA匹配比格犬急性同种异体移植排斥的有效口服免疫抑制方案。在临床实践中应用前,需要进一步研究其剂量、毒性及与当前免疫抑制方案相比的疗效。