摘要
目的以程序化肾活检评估低水平与标准水平他克莫司(FK506)的免疫抑制方案的疗效及其安全性。方法采用前瞻性、开放、随机对照研究,将48例首次接受尸体肾移植受者按随机数字分为两组:低水平FK506组(低FK506组,24例)和标准水平FK506组(标准FK506组,24例)。两组患者均采用麦考酚吗乙酯(MMF)+FK506+肾上腺皮质激素(激素)的三联免疫抑制方案,两组的MMF与激素用法相同。标准FK506组的FK506血药谷浓度:在入组后前3个月维持在10～12 ng/ml,3个月后维持在8～10 ng/ml。低FK506组的FK506血药谷浓度:入组后头2个月为8～10 ng/ml,第3个月为3～7 ng/ml,3个月后为3～5 ng/ml。术后定期随访1年,内容包括测定FK506血药谷浓度,检测肾功能[血清肌酐(Scr)、内生肌酐清除率(endogenous creatinine clearancerate,Ccr)]、空腹血糖、糖化血红蛋白、血清白蛋白、血脂。同时于术后3个月和12个月予以程序化移植肾活组织检查(活检),了解急性排斥反应(AR)发生情况、病理损伤指标评分及慢性移植物损伤指数(chronic allograft damage index,CADI)变化。观察术后1年的人、肾存活率及不良事件发生情况。结果移植术后1年,与标准FK506组比较,低FK506组:(1)FK506血药谷浓度较低(P<0.01),且达到目标水平的患者所占比例较高;(2)Ccr水平较高,(83±14)ml/min比(62±16)ml/min,P<0.05;(3)血糖水平较低(P<0.05);(4)根据程序化肾活检的结果,间质纤维化、肾小管萎缩和肾小球硬化评分较低(均为P<0.05);(5)AR发生率及其严重程度相似,术后1年人、肾存活率相近,均为100%(均为P>0.05)(6)术后1年的肺部感染与新发糖尿病的发生率较低(分别为P<0.05和P<0.01)。结论采用程序化肾活检评估疗效结果可靠,并有助于发现移植肾的慢性化改变,移植术后早期适度降低FK506血药谷浓度对于移植肾和患者均有较大益处,且不增加发生排斥反应的风险。
Objective To evaluate the effect and safety of modest tacrolimus（FK506） reduction by programming renal biospies.Methods A prospective,randomized,open study was designed and forty-eight recipients undergoing firstly cadaveric renal transplantation were divided randomly into two groups： low dose tacrolimus group（Lo-FK506 group,n=24） and standard dose tacrolimus group（St-FK506 group,n=24）.The recipients in both groups were treated with triple immunosuppression regimen including mycophenolate mofetil（MMF）,FK506 and adrenal cortex hormone.The FK506 blood trough concentration of St-FK506 group was maintained at 10-12 ng/ml in the first three months after study entry,and then at 8-10 ng/ml after three months.The FK506 blood trough concentration of Lo-FK506 group was maintained at 8-10 ng/ml in the first two months after study entry,3-7 ng/ml in third month,3-5 ng/ml after 3 months.All patients were followed up for one year.The FK506 blood trough concentration,renal function[serum creatinine（Scr）,endogenous creatinine clearance rate（Ccr）],fasting blood glucose,glycosylated hemoglobin,seralbumin and blood fat were examined and recorded regularly.At the same time,acute rejection（AR） occurrence,pathological damage index score and chronic allograft damage index（CADI）of recipients were evaluated by using renal graft biopsy（FNA） at month 3 and 12 post-transplantation.The 1-year survival rate of patients /grafts and the incidence of adverse event were observed.Results One year follow-up post-transplantation,FK506 blood trough concentration in the Lo-FK506 group was lower compared with St-FK506 group（P〈0.01）,but most of the patients reached the target level.The level of Ccr in Lo-FK506 group was higher than that of St-FK506 group[（83±14） ml / min vs（62 ±16） ml/min,P〈0.05].The level of glucose was lower in Lo-FK506 group than that of St-FK506 group（P〈0.05）.According to the results of programming renal biopsies,interstitial fibrosis,tubular atrophy and glomerulosclerosis score were also lower in Lo-FK506 group（all in P〈0.05）.The incidence,severity of AR as well as 1-year survival rates of patient /graft was similar in both groups（P〈0.05）.The incidence of pulmonary infection and de novo diabetes one year posttransplant was significantly lower in Lo-FK506 group compared with St-FK506 group（P〈0.05 and P〈0.01 respectively）.Conclusion It is reliable and helpful to evaluate the efficacy of modest tacrolimus reduction by programming renal biopsies and to find the chronic pathological changes of transplanted grafts.Modest reduction of the FK506 blood trough concentration in the early stage after transplantation is good for kidney grafts and recipients without increasing the risk of rejection.
出处
《器官移植》
CAS
2012年第2期95-101,共7页
Organ Transplantation
基金
国家自然科学基金项目(81070593)
关键词
肾移植
他克莫司
程序化肾活检
急性排斥反应
慢性移植物损伤指数
内生肌酐清除率
Kidney transplantation
Tacrolimus
Programming renal biopsy
Acute rejection
Chronic allograft damage index
Endogenous creatinine clearance rate
