Best N G, Trull A K, Tan K K, Spiegelhalter D J, Cary N, Wallwork J
MRC Biostatistics Unit, Institute of Public Health, United Kingdom.
Transplantation. 1996 Nov 27;62(10):1429-35. doi: 10.1097/00007890-199611270-00009.
We have attempted to determine the optimal clinical use of cyclosporine during the first 3 months after heart transplantation. We used multiple logistic regression to quantify how blood cyclosporine concentrations and other potential risk factors influence the risk of histologically confirmed acute rejection in 111 heart transplant recipients. A 50% increase in cyclosporine concentration was associated with a 15% reduction in risk of rejection in the subsequent 5 days (P=0.002). Increasing oral corticosteroid dose also protected against rejection (P=0.01). Rejection was over 2.5 times more likely during the first 20 postoperative days, and patients with 2 HLA-DR mismatches who were transplanted for cardiomyopathy or who had multiple previous rejection episodes were predisposed to further rejection (P<0.01). High short-term variability in cyclosporine concentrations was weakly associated with risk of rejection (P=0.1). Investigation of threshold levels for the cyclosporine concentration-effect relationship suggested that concentrations above 375 microgram L(-1) provide optimal protection against acute cardiac allograft rejection. This result yields an objectively defined therapeutic threshold for targeting early cyclosporine concentrations following heart transplantation, although the upper end of the range will depend on the individual's susceptibility to nephrotoxicity and infection.
我们试图确定心脏移植后前3个月环孢素的最佳临床应用方式。我们运用多元逻辑回归分析，以量化血中环孢素浓度及其他潜在风险因素对111名心脏移植受者经组织学证实的急性排斥反应风险的影响。环孢素浓度增加50%与随后5天内排斥反应风险降低15%相关（P = 0.002）。增加口服皮质类固醇剂量也可预防排斥反应（P = 0.01）。术后前20天内发生排斥反应的可能性超过2.5倍，因心肌病接受移植或既往有多次排斥反应发作的2个HLA - DR错配患者更易发生进一步排斥反应（P < 0.01）。环孢素浓度的高短期变异性与排斥反应风险弱相关（P = 0.1）。对环孢素浓度 - 效应关系阈值水平的研究表明，浓度高于375微克/升可提供针对急性心脏同种异体移植排斥反应的最佳保护。这一结果得出了心脏移植后早期环孢素浓度目标的客观定义治疗阈值，尽管该范围的上限将取决于个体对肾毒性和感染的易感性。
