Khauli R B, Wilson J M, Baker S P, Valliere S A, Lovewell T D, Stoff J S
Transplantation Service, University of Massachusetts Medical Center, Worcester 01655, USA.
J Urol. 1995 Jun;153(6):1805-9; discussion 1810. doi: 10.1016/s0022-5347(01)67315-4.
The updated data on 61 consecutive cadaveric transplants performed at our institution from 1987 to 1990 (followup 31 to 82 months, median 54 months) were analyzed with emphasis on cyclosporine monitoring and long-term results. All patients received triple therapy with cyclosporine induction, azathioprine and prednisone regardless of graft function, and they were preferentially placed on the calcium blocker nifedipine. We monitored 12-hour cyclosporine trough levels in whole blood using high performance liquid chromatography and the dose was adjusted to maintain levels at 150 ng./ml. or greater for the first 3 months. In 17 of 61 patients (28%) 22 rejection episodes occurred and 20 nephrotoxicity episodes occurred in 17 of 61 patients (28%). There was no significant difference in the mean cyclosporine levels among 32 rejection, nonrejection, nephrotoxic and nonnephrotoxic cases at any interval. Rejection occurred by 1 month in 13 (76%) and by 3 months in 15 (88%) of 17 patients. Comparisons were made in the first month to define the desirable cyclosporine levels by calculating the mean cyclosporine only within 10 to 14 days of rejection or nephrotoxicity events. The mean cyclosporine level before rejection was significantly lower than that for nephrotoxicity (188 +/- 113 versus 304 +/- 62 ng./ml., p < 0.01). The median cyclosporine level for first month rejection was also significantly lower than that for nonrejection (156 versus 218 ng./ml., p < 0.05) and it was significantly greater for nephrotoxicity versus nonnephrotoxicity (272 versus 218 ng./ml., p < 0.05). Of 13 rejections in the first month 10 (77%) were associated with mean levels of less than 210 ng./ml. Actuarial graft survival at 1, 3 and 5 years was 93.4%, 87.8% and 78.5%, respectively. The 3-year graft survival was significantly worse for patients who experienced acute rejection episodes versus those who did not (68.8% versus 96.7%, p < 0.05) but it was not different for nephrotoxic versus nonnephrotoxic groups (85.6% versus 79.6%). Long-term function was not influenced by the occurrence of acute nephrotoxicity events. These findings confirm the efficacy of triple therapy with induction cyclosporine in cadaveric transplantation, yielding improved short-term and intermediate graft survival without any adverse effects on long-term graft function. Specific cyclosporine level monitoring is invaluable, particularly initially, with high target levels of 200 ng./ml. or greater. The use of calcium blockers may have allowed higher cyclosporine dosing in the first 3 months, mitigating against cyclosporine associated chronic nephrotoxicity.
分析了1987年至1990年在我们机构进行的61例连续尸体移植的最新数据（随访31至82个月，中位时间54个月），重点关注环孢素监测和长期结果。所有患者无论移植肾功能如何，均接受环孢素诱导、硫唑嘌呤和泼尼松的三联疗法，并优先使用钙通道阻滞剂硝苯地平。我们使用高效液相色谱法监测全血中环孢素12小时谷浓度，并调整剂量以在前3个月将浓度维持在150 ng/ml或更高。61例患者中有17例（28%）发生了22次排斥反应，61例患者中有17例（28%）发生了20次肾毒性事件。在任何时间段，32例排斥、非排斥、肾毒性和非肾毒性病例的平均环孢素水平均无显著差异。17例患者中，13例（76%）在1个月内发生排斥反应，15例（88%）在3个月内发生排斥反应。在第一个月进行比较，通过仅计算排斥或肾毒性事件发生后10至14天内的平均环孢素水平来确定理想的环孢素水平。排斥反应前的平均环孢素水平显著低于肾毒性的平均环孢素水平（188±113 ng/ml对304±62 ng/ml，p<0.01）。第一个月排斥反应的中位环孢素水平也显著低于非排斥反应的中位环孢素水平（156对218 ng/ml，p<0.
