Gurk-Turner Cheryle, Airee Richa, Philosophe Benjamin, Kukuruga Debra, Drachenberg Cinthia, Haririan Abdolreza
Department of Pharmacy, University of Maryland Medical Center, Baltimore, MD 21201, USA.
Transplantation. 2008 May 27;85(10):1425-30. doi: 10.1097/TP.0b013e31816dd596.
Thymoglobulin (rATG) has become the agent of choice for induction therapy in high immunological risk kidney transplant recipients. However, its optimal dosing in this subgroup has not been studied.
To evaluate the effect of total rATG dosing on graft outcomes in such patients, we conducted a retrospective cohort study of 96 adult patients who received repeat transplants (85%) or had panel reactive antibody more than 40% (19%) and were maintained on tacrolimus, mycophenolate mofetil, and steroid. Group 1 (n=33) received less than or equal to 7.5 and group 2 (n=63) received more than 7.5 mg/kg rATG. Graft and patient survival, incidence of acute rejection (AR), and 12-month serum creatinine (SCr) were examined.
The groups were comparable regarding demographics, donor source, retransplantation, panel reactive antibody, and human leukocyte antigen mismatch. Group 2 had more African Americans (44.4% vs. 21.2%, P=0.03). During the 25.4+/-18.0 months follow-up graft survival was 82.5% and 79.4%, respectively (P=0.54). Three in group 1 and four in group 2 died (P=0.65). The incidence of biopsy proven AR during the first 12-months did not differ between the groups (9.5% vs. 8.8%, respectively, P=0.9). SCr at 12 months was 1.6+/-0.7 in group 1 and 1.8+/-1.0 in group 2 (P=0.3). There was no independent association between rATG dose and graft survival (hazard ratio: 0.85, P=0.79, 95% CI: 0.26-2.7 for group 2 vs. 1) or 1-year SCr (regression coefficient=0.02 for ln(SCr), P=0.3; 95%CI: -0.01 to 0.6).
Our results suggest that in high risk kidney transplant recipients total rATG doses less than or equal to 7.5 mg/kg are safe and effective in achieving a low rate of AR and graft outcomes comparable to higher doses.
胸腺球蛋白（rATG）已成为高免疫风险肾移植受者诱导治疗的首选药物。然而，该亚组患者的最佳剂量尚未得到研究。
为评估rATG总剂量对这类患者移植结局的影响，我们对96例成年患者进行了一项回顾性队列研究，这些患者接受了再次移植（85%）或群体反应性抗体超过40%（19%），并接受他克莫司、霉酚酸酯和类固醇维持治疗。第1组（n = 33）接受的rATG剂量小于或等于7.5mg/kg，第2组（n = 63）接受的rATG剂量大于7.5mg/kg。检查移植和患者生存率、急性排斥反应（AR）发生率以及12个月时的血清肌酐（SCr）。
两组在人口统计学、供体来源、再次移植、群体反应性抗体和人类白细胞抗原错配方面具有可比性。第2组非裔美国人更多（44.4%对21.2%，P = 0.03）。在25.4±18.0个月的随访期间，移植存活率分别为82.5%和79.4%（P = 0.54）。第1组有3人死亡，第2组有4人死亡（P = 0.65）。两组在最初12个月内活检证实的AR发生率无差异（分别为9.5%对8.8%，P = 0.9）。第1组12个月时的SCr为1.6±0.7，第2组为1.8±1.0（P = 0.3）。rATG剂量与移植存活率（风险比：0.85，P = 0.79，第2组对第1组的95%CI：0.26 - 2.7）或1年SCr之间无独立关联（ln(SCr)的回归系数 = 0.02，P = 0.3；95%CI：-0.01至0.6）。
我们的结果表明，在高风险肾移植受者中，rATG总剂量小于或等于7.5mg/kg在实现低AR发生率和与更高剂量相当的移植结局方面是安全有效的。
