Halloran P F, Aprile M A, Farewell V, Ludwin D, Smith E K, Tsai S Y, Bear R A, Cole E H, Fenton S S, Cattran D C
Toronto General Hospital, Ontario, Canada.
Transplantation. 1988 Aug;46(2):223-8.
We examined the factors determining graft survival in 200 consecutive cadaveric renal transplants managed on a quadruple-therapy protocol: Minnesota antilymphoblast globulin, cyclosporine, azathioprine, and low-dose prednisone. Perioperative central venous pressure monitoring and volume expansion were emphasized. To avoid CsA nephrotoxicity in the early posttransplant period, patients were treated with ALG until renal function was established (a mean of 7 days). Therapeutic CsA levels were achieved before ALG was discontinued. Azathioprine was used to supplement CsA in patients with nephrotoxicity or rejection. Twelve-month graft survival was 85% (first transplants 86%, retransplants 79%), with patient survival of 95%. ALG was not associated with excessive clinical cytomegalovirus infections, which occurred in 5% of patients, or with malignancy. When 3 technical failures were excluded, an analysis of numerous factors in the pretransplant and peritransplant period revealed that the strongest correlate of one-year graft survival was early renal function. Grafts with delayed function (DF) had 75% survival, compared with 91% for grafts with good early function (EF). A multivariate analysis confirmed this association: the relative risk of graft loss was increased 2.86 times for DF compared with EF. The mechanism of the deleterious effect of DF was apparently multifactorial: the DF group, by definition, contained all the kidneys that never functioned, but some risk also persisted in kidneys that achieved function. One reason for this may be that DF kidneys that achieved function had higher mean serum creatinine values at 1 month: elevated serum creatinine values at 1 month were strongly associated with increased risk of graft loss regardless of initial function. There was also a higher number of rejection episodes diagnosed in the DF group. These observations suggest that early renal function is a major determinant of graft outcome and should be a target for efforts to further improve renal graft survival.
我们研究了在采用四联疗法方案（明尼苏达抗淋巴细胞球蛋白、环孢素、硫唑嘌呤和小剂量泼尼松）管理的200例连续性尸体肾移植中决定移植物存活的因素。强调围手术期中心静脉压监测和容量扩充。为避免移植后早期环孢素肾毒性，患者接受抗淋巴细胞球蛋白治疗直至肾功能确立（平均7天）。在停用抗淋巴细胞球蛋白之前达到治疗性环孢素水平。硫唑嘌呤用于补充有肾毒性或排斥反应患者的环孢素。12个月移植物存活率为85%（首次移植86%，再次移植79%），患者存活率为95%。抗淋巴细胞球蛋白与5%患者发生的临床巨细胞病毒感染过多或恶性肿瘤无关。排除3例技术失败后，对移植前和围移植期的众多因素进行分析显示，1年移植物存活的最强相关因素是早期肾功能。功能延迟（DF）的移植物存活率为75%，而早期功能良好（EF）的移植物存活率为91%。多因素分析证实了这种关联：与EF相比，DF移植物丢失的相对风险增加了2.86倍。DF有害作用的机制显然是多因素的：根据定义，DF组包含所有从未发挥功能的肾脏，但在已发挥功能的肾脏中也存在一些风险。原因之一可能是已发挥功能的DF肾脏在1个月时平均血清肌酐值较高：无论初始功能如何，1个月时血清肌酐值升高与移植物丢失风险增加密切相关。DF组诊断出的排斥反应发作次数也更多。这些观察结果表明，早期肾功能是移植物结局的主要决定因素，应成为进一步提高肾移植存活率努力的目标。
